Tsotras, M., Charbonneau, J. A., Lepage, C. ...
· neuroscience
· Center of Biomedical Imaging, Department of Radiology, NYU Grossman School of Medicine, New York, NY
· biorxiv
Large-scale brain networks are vulnerable to change with aging and become dysregulated. How these networks are altered at the cellular level remains unclear owing to challenges of bridging data across scales. Here, we integrate in vivo cortical similarity networks with whole brai...
Large-scale brain networks are vulnerable to change with aging and become dysregulated. How these networks are altered at the cellular level remains unclear owing to challenges of bridging data across scales. Here, we integrate in vivo cortical similarity networks with whole brain spatial transcriptomics to characterize the aging brain in a lifespan cohort of macaques (N=64, ages 1-26 years). Deep-layer excitatory neurons and oligodendrocytes emerged as dominant correlates of cortical similarity, linking infragranular cell type composition to macroscopic network structure. Age-related declines in network strength were most pronounced in transmodal networks, including default mode and limbic, and aligned with regions enriched in inhibitory and glial cell types. Parvalbumin-enriched chandelier cells showed the strongest association with regional vulnerability, suggesting a role in network disconnection. Cell-type enrichment was conserved across species, with both human and macaque transcriptomic data aligning with the cortical functional hierarchy. These findings uncover a cellular basis for cortical network aging and highlight the value of imaging-transcriptomic integration across scales.
Longevity Relevance Analysis
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The paper identifies cellular correlates of cortical network aging in primates, linking specific cell types to age-related changes in brain network structure. This research is relevant as it explores the cellular mechanisms underlying aging, contributing to the understanding of the aging process itself rather than merely addressing age-related diseases.
Mohankumar Chandrakanth, Nishant Kumar, Chand Sura ...
· Journal of evolutionary biology
· Integrated Genetics and Evolution Laboratory (IGEL), Department of Biology, Ashoka University, Sonipat, Haryana, India, 131029.
· pubmed
Life-history traits such as body size, reproduction, survival, and stress resistance are fundamental to an organism's fitness and are highly influenced by nutritional environments across life stages. In this study, we employed a full factorial experimental design to investigate t...
Life-history traits such as body size, reproduction, survival, and stress resistance are fundamental to an organism's fitness and are highly influenced by nutritional environments across life stages. In this study, we employed a full factorial experimental design to investigate the effects of isocaloric diets (diets with equal caloric content but differing macronutrient composition) on key life-history traits in an outbred Drosophila melanogaster population. Our results demonstrated significant diet-induced plasticity, with male wing length (a proxy for body size) being influenced by the developmental diet; males reared on carbohydrate-rich developmental diets had larger wings as adults. Fertility increased with protein-rich diets at both developmental and adult stages, reaffirming the critical role of dietary protein in enhancing reproductive success. Lifespan exhibited sexually dimorphic responses to diet: carbohydrate-rich developmental diets extended male lifespan, while carbohydrate-rich adult diets reduced lifespan in both sexes. Stress resistance traits, including starvation and desiccation resistance, were unaffected by developmental diets but were influenced by adult diets, with carbohydrate-rich adult diets enhancing survival under both stress conditions in males and females. Importantly, while most traits exhibited additive effects of nutrition across life stages, a marginal interaction for male starvation resistance suggests that developmental and adult diets can interact in a trait- and sex-specific manner. Moreover, associations between dietary effects on life-history traits were context-dependent, driven primarily by adult diets and varying by sex. These findings emphasize the profound role of stage-specific nutritional environments in modulating life-history traits and their correlations, offering valuable insights into how organisms may adapt to changing ecological conditions and highlighting the importance of considering both developmental and adult dietary contexts in evolutionary studies.
Longevity Relevance Analysis
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The paper claims that dietary composition during developmental and adult stages significantly influences life-history traits, including lifespan and reproductive success in Drosophila melanogaster. The study's focus on how nutritional environments affect lifespan and stress resistance traits provides insights into potential mechanisms underlying aging and longevity, making it relevant to the field.
Kawasaki, H., Sato, T., Ishida, N.
· physiology
· Institute for Foundation for Advancement of International Science
· biorxiv
Cannabidiol (CBD), a non-psychoactive cannabinoid, has been studied for its various health-promoting effects recently. This study investigates the effects of dietary CBD to the circadian clock of Drosophila melanogaster as a model animal and its many physiological effect to flies...
Cannabidiol (CBD), a non-psychoactive cannabinoid, has been studied for its various health-promoting effects recently. This study investigates the effects of dietary CBD to the circadian clock of Drosophila melanogaster as a model animal and its many physiological effect to flies. We showed that CBD extended the period of locomotor activity in a dose-dependent manner, suggesting its influence on the circadian clock. Additionally, CBD improved sleep quality and extended lifespan under starvation conditions. The study also revealed enhanced rhythmicity in Close Proximity (CP) rhythm and increased eggs reproduction with dietary CBD supplementation. Furthermor, CBD attenuates age-related motor dysfunction in wild-type and Parkinson\'s disease (PD) model in Drosophila. These findings strongly suggest that appropriate amount of CBD affects the circadian rhythms, sleep, life span, CP rhythm, egg reproduction and motor function of Drosophila melanogaster, and providing a basic data for exploring its potential applications in managing circadian-related disorders in other animals.
Longevity Relevance Analysis
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Cannabidiol (CBD) extends lifespan and improves various physiological functions in Drosophila melanogaster. The study investigates mechanisms that may influence aging processes, making it relevant to longevity research.
Shang, Y., Wu, H., Pan, D.
· cancer biology
· Yi Shang Bio
· biorxiv
Aging is a major risk factor for the development of many cancers, yet the mechanisms underlying this increased susceptibility remain incompletely understood. Traditionally, the accumulation of genetic mutations over time has been considered a primary driver of age-related tumorig...
Aging is a major risk factor for the development of many cancers, yet the mechanisms underlying this increased susceptibility remain incompletely understood. Traditionally, the accumulation of genetic mutations over time has been considered a primary driver of age-related tumorigenesis. However, emerging evidence highlights the critical role of the aging tissue microenvironment -- including changes in immune, stromal, and epithelial compartments -- in shaping cancer initiation and progression. In this study, we employed integrated single-cell and spatial transcriptomics to systematically characterize age-associated alterations in human skin and skin cancers. Our analysis uncovered widespread, cell type-specific transcriptional reprogramming with age, revealing key pathways and cellular populations that may contribute to a pro-tumorigenic environment. Notably, we identified a previously unrecognized fibroblast subtype marked by SFRP2 expression, which expands with age and is associated with poor prognosis in basal cell carcinoma. These fibroblasts appear to enhance Wnt signaling within the tumor niche, suggesting a potential mechanism by which the aging stroma supports malignancy. Collectively, our findings shed light on how age-related changes in tissue ecosystems may predispose to cancer and point to novel therapeutic opportunities for targeting the aged tumor microenvironment.
Longevity Relevance Analysis
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The paper identifies an aging-associated fibroblast subtype that enhances Wnt signaling in tumors, suggesting a mechanism by which the aging stroma supports malignancy. The study addresses age-related changes in the tissue microenvironment that contribute to cancer, which is relevant to understanding the root causes of aging and its implications for age-related diseases.
Ali Al-Samydai, Farah Al-Mamoori, Amal Mayyas ...
· Molecular diversity
· Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
· pubmed
Sirtuin-6 (SIRT6) is a NAD+-dependent deacetylase that maintains genome stability, metabolic regulation, and cellular stress responses, making it an attractive target for therapeutic intervention in metabolic and age-related diseases. Despite its biological importance, the identi...
Sirtuin-6 (SIRT6) is a NAD+-dependent deacetylase that maintains genome stability, metabolic regulation, and cellular stress responses, making it an attractive target for therapeutic intervention in metabolic and age-related diseases. Despite its biological importance, the identification of potent SIRT6 modulators remains limited. In this study, we applied an integrative computational approach combining cheminformatics, network pharmacology, molecular docking, and molecular dynamics simulations to explore new inhibitory candidates targeting SIRT6. A curated dataset of 78 CHEMBL compounds was used to develop robust multi-fingerprint QSAR models using Random Forest algorithms, validated through Y-randomization, external testing, and applicability domain analysis. Network pharmacology analysis revealed functional associations between SIRT6 and key regulatory proteins such as NAMPT, CD38, and HIF1A, highlighting its involvement in NAD⁺ biosynthesis and cellular stress pathways. Molecular docking identified CHEMBL50 (Quercetin) and CHEMBL4217987 as top candidates with favorable interactions at the SIRT6 catalytic site. These complexes were further evaluated through 200 ns MD simulations. Binding stability was confirmed using MM-GBSA free energy calculations, dynamic cross-correlation matrix (DCCM), and principal component analysis (PCA), demonstrating energetically favorable and stable protein-ligand interactions. Overall, this study offers a predictive and mechanistic framework for SIRT6 inhibitor discovery and provides lead scaffolds for further optimization and experimental validation.
Longevity Relevance Analysis
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The study identifies potential SIRT6 inhibitors that could modulate pathways involved in metabolic regulation and cellular stress responses associated with aging. The research is relevant as it targets SIRT6, a protein linked to genome stability and metabolic processes that are crucial in the context of aging and age-related diseases.
Fulvio Lauretani, Marcello Maggio, Andrea M Pilotto ...
· Journal of the American Geriatrics Society
· Geriatric Clinic Unit, Medical Geriatric Rehabilitative Department, University Hospital of Parma, Parma, Italy.
· pubmed
To examine the structural, metabolic, and functional trajectories of neuromuscular decline in aging and identify key mechanisms and early biomarkers to guide interventions preserving function and independence.
To examine the structural, metabolic, and functional trajectories of neuromuscular decline in aging and identify key mechanisms and early biomarkers to guide interventions preserving function and independence.
Longevity Relevance Analysis
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The study aims to identify key mechanisms and early biomarkers of neuromuscular decline in aging. This research is relevant as it seeks to understand and potentially mitigate the underlying processes of aging, rather than merely addressing symptoms.
Hao Nie, Tianyi Ji, Zixin Wan ...
· Advanced science (Weinheim, Baden-Wurttemberg, Germany)
· Department of Geriatrics, Key Laboratory of Vascular ageing, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
· pubmed
Vascular smooth muscle cell (VSMC) senescence is a pivotal driver of atherosclerosis (AS), but molecular links to ageing-related dysfunction are unclear. It is aimed to identify regulators of VSMC senescence and develop clinical interventions for ageing-related AS. Using single-c...
Vascular smooth muscle cell (VSMC) senescence is a pivotal driver of atherosclerosis (AS), but molecular links to ageing-related dysfunction are unclear. It is aimed to identify regulators of VSMC senescence and develop clinical interventions for ageing-related AS. Using single-cell RNA sequencing of human atherosclerotic carotid arteries and immunofluorescence validation, activating transcription factor 3 (ATF3) is identified as central to VSMC senescence. Mechanistic studies employ SMC-specific ATF3 knockout mice, CUT&Tag-seq, RNA/protein interaction assays, and m6A epitranscriptomic analyses. To bridge discovery to therapy, high-throughput virtual screening is performed for ATF3-targeting compounds and functionally validated hits. ATF3 deficiency in VSMCs accelerates ageing-induced AS by promoting senescence. Multi-omics showed ATF3 activates ATG7, triggering autophagy, while cytoplasmic ATG7 enhances ATF3 nuclear translocation, establishing a positive feedback loop. Ageing increases m6A methylation and decreases the stability of Atf3 mRNA. Terazosin (TZ) diminishes the interaction between YTH N6-methyladenosine RNA binding protein F2 (YTHDF2) and Atf3 mRNA, helping to preserve Atf3 mRNA stability. TZ is a promising therapeutic strategy for delaying VSMC senescence and preventing AS. ATF3 protects against VSMC senescence and AS by orchestrating autophagy via a novel ATF3-ATG7 amplification loop. Repurposing TZ to stabilize ATF3 offers a translatable approach to combat ageing-driven cardiovascular disease.
Longevity Relevance Analysis
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ATF3 deficiency accelerates ageing-induced atherosclerosis by promoting vascular smooth muscle cell senescence, and repurposing terazosin may stabilize ATF3 to combat this process. The paper addresses the molecular mechanisms underlying vascular aging and proposes a therapeutic strategy that targets the root causes of age-related cardiovascular disease.
The MULTI Consortium, , Cao, H., Song, Z. ...
· health informatics
· Columbia University
· medrxiv
Leveraging clinical phenotypes, neuroimaging, proteomics, metabolomics, and epigenetics, biological aging clocks across organ systems and tissues have advanced our understanding of human aging and disease. In this study, we expand this biological aging clock framework to multi-or...
Leveraging clinical phenotypes, neuroimaging, proteomics, metabolomics, and epigenetics, biological aging clocks across organ systems and tissues have advanced our understanding of human aging and disease. In this study, we expand this biological aging clock framework to multi-organ magnetic resonance imaging (MRI) by developing 7 organ-specific MRI-based biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney, and pancreas. Leveraging imaging, genetic, proteomic, and metabolomic data from 313645 individuals curated by the MULTI consortium, we link the 7 MRIBAGs to 2923 plasma proteins, 327 metabolites, and 6477810 common genetic variants. These associations reveal organ-specific and cross-organ interconnection landscapes, identifying distinct molecular signatures related to organ aging. Genome-wide associations identify 53 MRIBAG-locus pairs. Genetic correlation and Mendelian randomization analyses further support organ-specific and cross-organ interconnections with 9 phenotype-based, 11 proteome-based, and 5 metabolome-based aging clocks, as well as 525 disease endpoints. Through functional gene mapping and Bayesian colocalization analysis linking evidence from genetics, proteomics, and metabolomics, we prioritize 9 druggable genes as targets for future anti-aging treatments. Finally, we demonstrate the clinical relevance of the 7 MRIBAGs in predicting disease endpoints (e.g., diabetes mellitus), all-cause mortality, and capturing differential and heterogeneous cognitive decline trajectories over 240 weeks of treatment with the Alzheimers disease drug (Solanezumab). Sex differences are evident across multiple organ systems, manifesting at structural, molecular, and genetic levels. In summary, we developed 7 MRI-based aging clocks that enhance the existing multi-organ biological aging framework, offer multi-scale insights into aging biology, and demonstrate clinical potential to advance future aging research.
Longevity Relevance Analysis
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The study develops 7 MRI-based biological aging clocks that link organ-specific aging to molecular signatures and disease endpoints. This research is relevant as it addresses biological aging mechanisms and their implications for longevity and age-related diseases, rather than merely treating symptoms.
Ines Sturmlechner, Abhinav Jain, Bin Hu ...
· CD8-Positive T-Lymphocytes
· Department of Immunology, Mayo Clinic, Rochester, MN, USA. [email protected].
· pubmed
Memory T cells are a highly heterogeneous collection of antigen-experienced cells that undergo dynamic adaptations upon antigen re-encounter and environmental signals. This heterogeneity hinders studies on memory T cell durability and age-related dysfunction. Using chronic Epstei...
Memory T cells are a highly heterogeneous collection of antigen-experienced cells that undergo dynamic adaptations upon antigen re-encounter and environmental signals. This heterogeneity hinders studies on memory T cell durability and age-related dysfunction. Using chronic Epstein-Barr virus (EBV) infection and barcode-enabled antigen tracing, we assess the influence of age on memory states at the level of single antigen-specific CD8
Longevity Relevance Analysis
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The paper claims that antigen specificity influences the aging trajectories of memory CD8⁺ T cells. This research is relevant as it explores the mechanisms underlying immune aging, which is a critical aspect of longevity and age-related dysfunction.
Brian O Diekman, Ming-Feng Hsueh
· Connective tissue research
· Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
· pubmed
Aging is the largest risk factor for the development of osteoarthritis (OA), a major contributor to increased years lived with disability. This review reflects on how age-related changes relevant to OA have been measured at various length scales. Key discoveries include increased...
Aging is the largest risk factor for the development of osteoarthritis (OA), a major contributor to increased years lived with disability. This review reflects on how age-related changes relevant to OA have been measured at various length scales. Key discoveries include increased chondrocyte DNA damage with age and the disruption of matrix homeostasis by cellular senescence. Epigenetic clocks have yet to show predictive value for OA, while transcriptomic changes and miRNA profiles are linked to aging and senescence. Protein biomarkers have gained traction in the context of post-traumatic OA and may also be useful in understanding risk profiles for age-related OA. Post-translational modifications provide insights into protein aging and the rate of matrix turnover at different joint sites. Non-enzymatic crosslinks also increase with age and may be responsible for changes to the mechanical properties of joint tissues. Finally, the walking speed declines with age and predicts incident OA. Despite these advances, more research is needed on age-related changes in tissues beyond cartilage. Efforts should be directed toward identifying biomarkers of aging that can integrate large studies on genetic risk factors with the deep phenotyping done in longitudinal cohort OA studies. Early intervention is crucial for treating OA and other age-related diseases, highlighting the importance of validating sensitive and predictive biomarkers that could support new treatment paradigms. Finally, reversing at least some aspects of age-related decline may be critical for improving joint function. Promising approaches include effective delivery of targeted senolytics and the use of partial reprogramming to rejuvenate chondrocytes.
Longevity Relevance Analysis
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The paper discusses the need for biomarkers of aging to improve understanding and treatment of osteoarthritis. It is relevant as it addresses the underlying mechanisms of aging and their impact on age-related diseases, rather than merely treating symptoms.
Kang, P. J., Mazak, H., Lee, S. S. ...
· cell biology
· The Ohio State University
· biorxiv
The small GTPase Cdc42 is a central regulator of cell polarity, but it is often hyperactivated in aged cells, contributing to senescence and aging in both yeast and animal cells. Yet, the mechanisms underlying its age-related upregulation remain poorly understood. Here, we examin...
The small GTPase Cdc42 is a central regulator of cell polarity, but it is often hyperactivated in aged cells, contributing to senescence and aging in both yeast and animal cells. Yet, the mechanisms underlying its age-related upregulation remain poorly understood. Here, we examine how Cdc42 levels change over successive divisions in budding yeast, which undergoes asymmetric cell division, leading to aging predominantly in mother cells. Using microfluidics-based live-cell imaging and genetic analyses, we find that Cdc42 protein is unevenly distributed between mother and daughter cells during division. Notably, daughter cells inherit lower levels of Cdc42, which helps them rejuvenate. This asymmetry depends on Cdc42s association with endomembranes and requires the presence of farnesylated Ydj1, an Hsp40/DnaJ chaperone tethered to the endoplasmic reticulum. Furthermore, maintaining proper Cdc42 levels relies on its interaction with Ydj1. These findings reveal a chaperone-mediated mechanism that controls Cdc42 partitioning during asymmetric division, linking it to cellular aging--a process that may be conserved in other asymmetrically dividing cells.
Longevity Relevance Analysis
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The paper claims that Cdc42 protein levels are unevenly distributed during asymmetric division, influencing cellular aging. This research addresses a mechanism related to the aging process, specifically how cellular components contribute to rejuvenation in daughter cells, which is relevant to understanding the root causes of aging.
Yuko Sogabe, Hirofumi Shibata, Mio Kabata ...
· Nature aging
· Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
· pubmed
There is robust evidence that senescence can be propagated in vitro through mechanisms including the senescence-associated secretory phenotype, resulting in the non-cell-autonomous induction of secondary senescence. However, the induction, regulation and physiological role of sec...
There is robust evidence that senescence can be propagated in vitro through mechanisms including the senescence-associated secretory phenotype, resulting in the non-cell-autonomous induction of secondary senescence. However, the induction, regulation and physiological role of secondary senescence in vivo remain largely unclear. Here we generated senescence-inducible mouse models expressing either the constitutively active form of MEK1 or MKK6 and mCherry, to map primary and secondary senescent cells. Our models recapitulate characteristic features of senescence and demonstrate that primary and secondary phenotypes are highly tissue- and inducer-dependent. Spatially resolved RNA expression analyses at the single-cell level reveal that each senescence induction results in a unique transcriptional profile-even within cells of the same cell type-explaining the heterogeneity of senescent cells in vivo. Furthermore, we show that interleukin-1β, primarily derived from macrophages, induces secondary phenotypes. Our findings provide insight into secondary senescence in vivo and useful tools for understanding and manipulating senescence during aging.
Longevity Relevance Analysis
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The paper claims that primary and secondary senescence phenotypes are tissue- and inducer-dependent, revealing unique transcriptional profiles in senescent cells. This research is relevant as it explores the mechanisms of senescence, which are fundamental to understanding aging and potential interventions to mitigate age-related decline.
Xiaoyu Guo, Chan Wei, Rui Liu ...
· Journal of agricultural and food chemistry
· Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, China.
· pubmed
The aging process is often accompanied by hepatic metabolic dysregulation and related complications, including lipid accumulation and fibrosis. Nutritional interventions are crucial for maintaining metabolic health. This study explored the effects of exogenous nucleotides (NTs) o...
The aging process is often accompanied by hepatic metabolic dysregulation and related complications, including lipid accumulation and fibrosis. Nutritional interventions are crucial for maintaining metabolic health. This study explored the effects of exogenous nucleotides (NTs) on liver health in aged SAMP8 mice over 9 months. Results demonstrated dietary NTs effectively improved liver pathology, increased body mass, enhanced antioxidant capacity, reduced lipid accumulation, downregulated lipid synthesis genes, and lowered fibrosis-related markers. Mechanistically, NTs downregulated purine biosynthesis, modulating lipid metabolism-related transcription factors to reduce lipid accumulation. Additionally, NTs enhanced the efficiency of glycolysis and increased ATP synthesis. Thus, NTs exhibited substantial effects in regulating energy metabolism, suppressing lipid synthesis, and combating fibrosis. However, the effects displayed a nonlinear dose-dependent relationship, and the precise impact of NT dosage on health remains challenging. This study advances our understanding of NTs' role in aging and metabolic dysregulation.
Longevity Relevance Analysis
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Dietary nucleotides improve liver health in aged mice by mitigating lipid dysregulation and fibrosis. The study addresses metabolic dysregulation associated with aging, suggesting a potential nutritional intervention to combat age-related liver issues, which is relevant to longevity research.
Naor Sagy, Chieh Chang, Maayan Gal ...
· GeroScience
· Department of Oral Biology, Goldschleger School of Dental Medicine, Gray Faculty of Medical and Health Sciences, Tel Aviv University, 69978, Tel Aviv, Israel.
· pubmed
Aging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss is a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly invest...
Aging is a major risk factor for a plethora of diseases. The information theory of aging posits that epigenetic information loss is a principal driver of the aging process. Despite this, the connection between epigenetic information loss and disease has not been thoroughly investigated. Here, we analyzed tissue-unique methylation patterns in healthy and diseased human organs, revealing that for several diseases these patterns degrade, regressing to a mean form. We interpret this as epigenetic information loss, where tissue-unique patterns erode. Information loss is not limited to diseases. Age-related erosion of unique methylation patterns was observed in some tissues and cells, while other tissues and cells diverged away from the mean. Our findings demonstrate that analyzing methylation patterns in tissue-unique sites can effectively distinguish between patients and healthy controls at least in some diseases, and underscore the role of epigenetic information loss as a common feature in various pathological conditions.
Longevity Relevance Analysis
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The paper claims that epigenetic information loss is a common feature of aging and various diseases, suggesting that analyzing methylation patterns can distinguish between healthy and diseased states. This research is relevant as it addresses a potential root cause of aging through the lens of epigenetics, which may lead to insights into lifespan extension and age-related diseases.
Shoko Mizutani, Kanji Furuya, Ayumi Mure ...
· EMBO reports
· Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
· pubmed
The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with Drosophila melanogaster as a model, we fed larvae on diets consisting of a variety of yeast mutants and explored the resu...
The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with Drosophila melanogaster as a model, we fed larvae on diets consisting of a variety of yeast mutants and explored the resulting histories that impacted adult lifespan. A larval diet comprised of yeast nat3 KO shortened the lifespan of male adults; and remarkably, this diet diminished the function of histone acetyltransferase Gcn5 in larvae. Concordantly, perturbation of Gcn5-mediated gene regulation in the larval whole body or neurons significantly contributed to the earlier death of adults. The nat3 KO diet is much more abundant in long-chain fatty acids and branched-chain amino acids (BCAAs) than the control yeast diet. Supplementing the control diet with a combination of oleic acid, valine, and acetic acid recapitulated the effects of the nat3 KO diet on the larval transcriptome and the lifespan of males. Our findings strongly suggest a causal link between a fatty acids- and BCAA-rich diet in developmental stages and lifespan reduction via the adverse effect on the Gcn5 function.
Longevity Relevance Analysis
(4)
The paper claims that a diet rich in fatty acids and branched-chain amino acids during the larval stage negatively impacts lifespan by diminishing the function of histone acetyltransferase Gcn5. This research is relevant as it explores the effects of early-life nutrition on lifespan, addressing potential mechanisms of aging rather than merely treating age-related symptoms.
Tangchang Xu, Xiaoyun Wu, Yifei Zhang ...
· Aging cell
· School of Life Sciences, Nanchang University, Nanchang, China.
· pubmed
Gut microbiota delays aging by regulating the immune, metabolic, and neurological functions of the host. However, current research on novel probiotics with antiaging properties significantly lags, impacting their application in clinical treatments. In this study, metagenomics, cu...
Gut microbiota delays aging by regulating the immune, metabolic, and neurological functions of the host. However, current research on novel probiotics with antiaging properties significantly lags, impacting their application in clinical treatments. In this study, metagenomics, culturomics, and probiotic property screening were used to identify Bifidobacterium pseudocatenulatum NCU-08 as a potential probiotic with anti-aging properties. In addition, B. pseudocatenulatum NCU-08 effectively improved the behavioral characteristics, significantly reduced the levels of the age-related protein β-galactosidase (β-gal) (BP: M = 0.81 vs. 1.13, p < 0.05), attenuated neuronal damage in the hippocampus, and improved the composition of the gut microbiota of senescence-accelerated mouse tendency-8 (SAMP8) mice. The targeted metabolomics suggested that L-tryptophan (L-Trp) may be a key substance for B. pseudocatenulatum NCU-08 to exert anti-aging effects (BP: M = 14878.6 ng/mL vs. 5464.99 ng/mL, p < 0.01). Mechanistically, using the aging model of SAMP8 mice and HT22 mouse hippocampal neuronal cells, it was found that B. pseudocatenulatum NCU-08 might enter the intestine to regulate L-Trp, and then transport it to the brain. In the brain, L-Trp was metabolized to NAD
Longevity Relevance Analysis
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Bifidobacterium pseudocatenulatum NCU-08 delays aging in SAMP8 mice by activating the Sirt1/P53/P21/Rb signaling pathway. This study addresses the potential of a probiotic to influence aging mechanisms, which is directly related to longevity research.
Pengfei Xu, Xiuli Zhang, Donghe Li ...
· Blood
· Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
· pubmed
Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic system throughout life, and their functional decline contributes to hematological disorders and organismal aging. Understanding the molecular mechanisms that govern HSC function is critical for developin...
Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic system throughout life, and their functional decline contributes to hematological disorders and organismal aging. Understanding the molecular mechanisms that govern HSC function is critical for developing interventions for treating and preventing aging-related diseases. Here, we show that DCAF8, a substrate recognition component of Cullin-RING E3 ubiquitin ligases, is highly expressed in HSCs and undergoes a progressive decline with age. Loss of DCAF8 in mice results in impaired function in HSCs, characterized by increased number yet decreased self-renewal capacity, which associates with cellular senescence and elevated DNA damage. Mechanistically, DCAF8 mediates the degradation of DOCK11, a guanine nucleotide exchange factor for CDC42. In the absence of DCAF8, DOCK11 accumulates, leading to elevated CDC42 activity and consequential loss of polarity of HSCs. Knocking out Dock11 mitigates the senescence, DNA damage, and self-renewal defects of Dcaf8-/- HSCs. This study highlights a critical role of DCAF8 in preventing HSC senescence via the DOCK11-CDC42 axis and suggests potential therapeutic targets for preventing functional decline in HSCs.
Longevity Relevance Analysis
(4)
Loss of DCAF8 impairs hematopoietic stem cell function through the DOCK11-CDC42 axis, leading to cellular senescence. The study addresses the molecular mechanisms underlying the functional decline of hematopoietic stem cells, which is a critical aspect of aging and age-related diseases, thus contributing to the understanding of longevity.
G R Scott Budinger, Navdeep S Chandel
· Genes & development
· Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA [email protected][email protected].
· pubmed
Mitochondria are no longer viewed solely as ATP- or metabolite-generating organelles but as key regulators of cellular signaling that shape physiologic aging. Contrary to earlier theories linking aging to mitochondrial DNA mutations and oxidative damage, current evidence shows th...
Mitochondria are no longer viewed solely as ATP- or metabolite-generating organelles but as key regulators of cellular signaling that shape physiologic aging. Contrary to earlier theories linking aging to mitochondrial DNA mutations and oxidative damage, current evidence shows that these factors do not causally limit physiologic aging. Instead, an evolving literature links age-related loss of mitochondrial signaling and function to important physiologic changes of aging. Moreover, mild inhibition of mitochondrial respiratory function with drugs like metformin promote health span. These findings open new paths for pharmacologically reprogramming mitochondrial signaling to extend healthy aging.
Longevity Relevance Analysis
(4)
The paper claims that age-related loss of mitochondrial signaling and function is a key factor in physiologic aging, suggesting that pharmacological reprogramming of mitochondrial signaling could extend healthy aging. This research addresses the root causes of aging rather than merely treating symptoms, making it relevant to longevity research.
Fan-Qian Yin, Xia-Yan Wang, Yong-Xuan Li ...
· Aging
· State Key Laboratory of Genetic Evolution and Animal Models, State Key Laboratory of Genetic Resources and Evolution, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.
· pubmed
Identifying aging-associated biomarkers applicable for multiple tissues is challenging but crucial for assessing tissue aging. Here, we obtained and analyzed 456 transcriptomes on 17 organs from 30 C57BL/6 J mice with different ages, revealing the consistently upregulated mRNAs o...
Identifying aging-associated biomarkers applicable for multiple tissues is challenging but crucial for assessing tissue aging. Here, we obtained and analyzed 456 transcriptomes on 17 organs from 30 C57BL/6 J mice with different ages, revealing the consistently upregulated mRNAs of
Longevity Relevance Analysis
(4)
The paper identifies aging-associated biomarkers through multiorgan transcriptomics in mice. This research is relevant as it aims to uncover molecular signatures related to aging, which could contribute to understanding the biological mechanisms of aging and potentially lead to interventions that address the root causes of aging.
Xueling Ma, Yonghe Ding, David Mondaca-Ruff ...
· npj aging
· Department of Biochemistry and Molecular Biology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
· pubmed
African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate that can be bred in captivity, making it an ideal model organism for aging studies. However, whether the animal can be used for studying cardiac aging and whether cellular senescence contribute ...
African turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate that can be bred in captivity, making it an ideal model organism for aging studies. However, whether the animal can be used for studying cardiac aging and whether cellular senescence contribute to this ageing process remain unclear. Here, we conducted a longitudinal study on the GRZ strain, aiming to identify phenotypic and functional markers for cardiac aging. We found that cardiac ageing in GRZ fish can be measured by comparing fish at 16 weeks to 8 weeks of age, using systemic markers such as body/fin coloration, body weight, BMI, cardiac ageing markers such as EF, E/A ratio, and swimming capacity, and cellular senescence markers such as SA-β-gal staining, p15/p16, γ-H2A.X, and SASP markers. Senolytic treatment with D (Dasatinib) and Q (Quercetin) from 12 to 16 weeks mitigated senescence and decelerated cardiac ageing. Together, our findings established GRZ as a useful vertebrate model for studying cardiac ageing and related cardiac senescence.
Longevity Relevance Analysis
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The study establishes Nothobranchius furzeri as a model for investigating cardiac aging and cellular senescence. The research is relevant as it explores mechanisms of aging and potential interventions, contributing to the understanding of the aging process rather than merely addressing age-related diseases.
Elisabetta Di Fede, Esi Taci, Silvia Castiglioni ...
· npj aging
· Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
· pubmed
Cellular senescence represents a permanent state of cell cycle arrest, also observed in neurodegenerative disorders. As p300 has been identified as an epigenetic driver of replicative senescence, we aimed to investigate whether in vitro p300 inhibition could rescue the stress-ind...
Cellular senescence represents a permanent state of cell cycle arrest, also observed in neurodegenerative disorders. As p300 has been identified as an epigenetic driver of replicative senescence, we aimed to investigate whether in vitro p300 inhibition could rescue the stress-induced premature senescence (SIPS) phenotype. We exploited 2D and 3D (brain organoids) in vitro models of SIPS using two different stressor agents. In addition, we combined the treatment with a p300 inhibitor and validated p300 role in SIPS by analyzing different senescence markers and the transcriptome in our models. Interestingly, p300 inhibition can counteract the DNA damage and SIPS phenotype, detecting a dysregulation of gene expression and protein translation associated with the senescence program. These findings highlight both the molecular mechanisms underlying senescence and p300 as a possible pharmacological target. Thus, targeting p300 and, by extension, senescent cells could represent a promising therapeutic strategy for age-related diseases such as neurodegenerative disorders.
Longevity Relevance Analysis
(4)
Inhibition of p300 can counteract stress-induced premature senescence and its associated phenotypes. This research addresses the mechanisms of cellular senescence, which is a fundamental aspect of aging and age-related diseases, suggesting a potential therapeutic target for longevity.
Minwen Jie, Tong Feng, Fengjuan Hu ...
· Frailty
· Department of Gastroenterology and Hepatology and Laboratory of Aging and Cancer, National Clinical Research Center for Geriatrics and State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
· pubmed
Frailty, a geriatric syndrome, is characterized by the age-related deterioration of physical capabilities and multiple organ systems. However, its age-associated and age-independent mechanisms remain vague, impeding prevention and clinical intervention. Here, the physical frailty...
Frailty, a geriatric syndrome, is characterized by the age-related deterioration of physical capabilities and multiple organ systems. However, its age-associated and age-independent mechanisms remain vague, impeding prevention and clinical intervention. Here, the physical frailty status of young and old mice estimated using the frailty phenotype and frailty index values was used to divide mice into non-frail young/old (NF-Y/NF-O) and frail old (F-O) groups. Age-associated and age-independent transcriptional changes in frailty were investigated using single-cell RNA sequencing to profile transcriptomes in various cell types in limb muscles. We investigated the ratio of cell types, transcriptional regulation networks, and cell-cell communications in 15 major cell types in mice during relatively healthy aging (RHA), age-associated frailty (AAF), and age-independent frailty (AIF). Each group of RHA, AAF or AIF genes exhibited one major expression pattern and transcriptional regulation network. Besides its unique pattern, genes in the AAF group faintly exhibited the two major patterns seen in the AIF and RHA groups. B cells and satellite cells in both the AIF and AAF groups showed the most down-regulated and up-regulated differentially expressed genes, respectively. The transcriptional pattern of B cells, which showed stronger transcriptional changes than satellite cells in the AIF process, was validated by sorting B cells and performing SMART-sequencing. Thus, by analyzing these molecular events at the single-cell level, our study revealed the specific expression patterns and transcriptional heterogeneities of candidate cell types involved in relatively healthy aging and physical frailty, laying a foundation to characterize the detailed mechanisms and presenting possible therapeutic strategies for physical frailty.
Longevity Relevance Analysis
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The study identifies transcriptional heterogeneity in aging and physical frailty in mice, suggesting potential mechanisms and therapeutic strategies for addressing frailty. The research is relevant as it explores the underlying molecular changes associated with aging and frailty, which are critical for understanding and potentially mitigating age-related decline.
Bérénice A Benayoun, Alison Kochersberger, Jennifer L Garrison
· Genes & development
· Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA; [email protected][email protected].
· pubmed
Ovarian aging is a critical yet understudied driver of systemic aging in female bodies, with profound implications for female health and longevity. Despite its significance, we still know little about ovarian aging and its systemic effects on aging trajectories. With new efforts ...
Ovarian aging is a critical yet understudied driver of systemic aging in female bodies, with profound implications for female health and longevity. Despite its significance, we still know little about ovarian aging and its systemic effects on aging trajectories. With new efforts over the past few years, interest in the field has been growing and there is momentum to address these questions. This review highlights the importance of leveraging modern tools and approaches to better understand ovarian aging and its impact on health span. Specifically, we believe it will be useful for both aging researchers looking to go into research on ovarian aging and reproductive researchers looking to adopt more modern toolkit. We focus on menopause-a key marker of ovarian aging-as a lens through which to examine the current state of the field, identify limitations in existing research, and outline goals for future progress. By emphasizing cutting-edge techniques and emerging models, we seek to illuminate new pathways for research that could lead to improved strategies for managing ovarian aging and enhancing overall female health.
Longevity Relevance Analysis
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The paper claims that understanding ovarian aging can lead to improved strategies for managing it and enhancing female health. This research addresses a root cause of aging by exploring ovarian aging's systemic effects, which is crucial for advancing longevity research.
Samuel I Bloom, Jan Karlseder
· Genes & development
· The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
· pubmed
Aging is the greatest risk factor for most diseases. We propose that aging manifests as disease as a function of tumor-suppressive capabilities. Adequate tumor suppression results in cell death or an accumulation of damaged cells leading to inflammation and tissue dysfunction tha...
Aging is the greatest risk factor for most diseases. We propose that aging manifests as disease as a function of tumor-suppressive capabilities. Adequate tumor suppression results in cell death or an accumulation of damaged cells leading to inflammation and tissue dysfunction that underlies diseases such as cardiovascular disease, neurodegenerative diseases, or type 2 diabetes. Conversely, inadequate tumor suppression leads to cancer. Telomeres are central to this process because they oppose hyperproliferation that is required for cancer initiation by enforcing two potent tumor suppressor mechanisms: senescence and crisis. Although senescent cells promote age-related diseases via inflammatory signaling, crisis cells have lost the p53 and RB pathways, have more unstable genomes, and harbor shorter telomeres, all of which could increase inflammation to a greater degree than is seen in senescence. This model emphasizes the intimate relationship between aging, telomeres, tumor suppression, and inflammation and suggests that crisis cells may represent an unexplored driver of inflammation in advanced age.
Longevity Relevance Analysis
(4)
The paper claims that crisis cells, which arise from inadequate tumor suppression and shorter telomeres, may drive inflammation in advanced age. This research is relevant as it explores the underlying mechanisms of aging and their relationship with tumor suppression and inflammation, potentially addressing root causes of age-related diseases.
Jesús Gil
· Genes & development
· MRC Laboratory of Medical Sciences (LMS), London W12 0NN, United Kingdom; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom [email protected].
· pubmed
The past 40 years have witnessed significant progress in aging research. Although aging was once considered a stochastic process, it is now understood to be regulated by pathways and processes that can be dissected with modern cellular and molecular biology approaches. The aberra...
The past 40 years have witnessed significant progress in aging research. Although aging was once considered a stochastic process, it is now understood to be regulated by pathways and processes that can be dissected with modern cellular and molecular biology approaches. The aberrant accumulation of cells undergoing cellular senescence and an increase in chronic, sterile inflammation are two of those aging hallmarks. Here we discuss how these processes are connected and how the relationship between senescent cells and the immune system dictates the extent of inflammatory processes contributing to age-related dysfunction and disease.
Longevity Relevance Analysis
(4)
The paper discusses the connection between cellular senescence, inflammation, and the immune system in the context of age-related dysfunction. This research is relevant as it addresses underlying mechanisms of aging, which could inform strategies for longevity and age-related disease prevention.
Ioannis Oikonomakos, Richard Siow, Stefan R Bornstein ...
· Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
· Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
· pubmed
Aging is marked by a gradual decline in multiple physiological functions, increasing the risk of age-related disorders. Multiple factors have been identified as contributors to aging, many of which are regulated by the hypothalamus. Growth hormone-releasing hormone (GHRH) produce...
Aging is marked by a gradual decline in multiple physiological functions, increasing the risk of age-related disorders. Multiple factors have been identified as contributors to aging, many of which are regulated by the hypothalamus. Growth hormone-releasing hormone (GHRH) produced in the hypothalamus is a key regulator of growth hormone (GH) secretion. With aging, both GHRH and GH levels decline, leading to muscle loss, increased fat accumulation, metabolic dysregulation, and cognitive impairments. GH replacement therapy has been explored as a potential intervention to counteract these effects; however, its long-term use is associated with significant risks, including metabolic disturbances, cardiovascular complications, and potential cancer promotion. In contrast, studies suggest that GHRH-based therapies can improve body composition, muscle strength, cognitive function, and cardiovascular health while avoiding the risks linked to direct GH administration. Additionally, preclinical findings indicate that GHRH agonists may offer cardioprotective and immunomodulatory benefits. In this review, we summarize current knowledge on the roles of GHRH and GH in aging, highlight the limitations of GH-based therapies, and discuss the potential of GHRH-based approaches in mitigating age-related decline and improving health span.
Longevity Relevance Analysis
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GHRH-based therapies may improve health span by mitigating age-related decline. The paper discusses the role of GHRH in aging and its potential therapeutic applications, focusing on addressing root causes of aging rather than merely treating symptoms.
Zhi-Peng Yang, Shui-Hong Lu, Yan-Hong Pan ...
· MicroRNAs
· Dongguan Key Laboratory of Aging and Anti-Aging, Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Cardiovascular Center, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, P.R. China.
· pubmed
Senescence of vascular endothelial cells leads to endothelial dysfunction and exacerbates atherosclerosis. In this study, we presented evidence that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) could delay endothelial cell senescence, promote en...
Senescence of vascular endothelial cells leads to endothelial dysfunction and exacerbates atherosclerosis. In this study, we presented evidence that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) could delay endothelial cell senescence, promote endothelial cell proliferation, and enhance angiogenic activity in vitro. The miRNA profiling analysis revealed a high expression of miR-143-3p in hucMSC-Exos, which was further upregulated in endothelial cells treated with hucMSC-Exos. Silencing miR-143-3p induced endothelial cell senescence, as evidenced by increased senescence-associated β-galactosidase activity, reduced cell proliferation, and inhibited tubular formation; conversely, overexpression of miR-143-3p exhibited opposite effects. Moreover, we found that miR-143-3p directly targeted Cyclooxygenase-2 (COX-2) and suppressed its translation, thus delaying endothelial cell senescence. These results suggested that hucMSC-Exos can delay endothelial cell senescence by transferring miR-143-3p. In summary, our data demonstrated the potential of hucMSC-Exos as an intervention against vascular aging.
Longevity Relevance Analysis
(4)
Exosomes derived from human umbilical cord mesenchymal stem cells can delay endothelial cell senescence by transferring miR-143-3p, which targets COX-2. This research addresses a mechanism related to vascular aging, which is a root cause of age-related diseases, thus contributing to the understanding of longevity.
Fontana, G. A., Singh, N. K., Rotankova, N. ...
· genomics
· ETHZ
· biorxiv
Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UVA radiation is the primary factor for photoaging due to its deep penetration into the dermis, and UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to ph...
Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UVA radiation is the primary factor for photoaging due to its deep penetration into the dermis, and UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to photoaging and cellular dysfunction. The most frequent mtDNA rearrangement is the common deletion (CD), characterized by the loss of nearly one-third of the genome, 4,977 base pairs. UV radiation exposure leads to the formation of the CD, however, a distinct characterization of UV-induced CD and the underlying molecular mechanisms driving its initiation remains unexplored. In this study, we showed that increasing doses of UV radiation led to an increase in the CD in human skin fibroblasts. We found that UVA induce the formation of the CD by increasing the cellular reactive oxygen species (ROS) and oxidized bases content in the mtDNA. Preconditioning cells with antioxidants prevented the accumulation of the UVA-induced CD, suggesting that this mutational mechanism is ROS-dependent. In stark contrast, UVB did not alter cellular ROS levels but increased the formation of cyclobutane pyrimidine dimers (CPD), leading to CD generation though a ROS-independent mechanism. We corroborated our findings by using a 3D human full-thickness skin equivalent model, where we detected UVA-dependent CD formation in both the epidermal and dermal layers of the skin. By analyzing bulk RNA from UVA-exposed human skin fibroblasts by RNA-Seq, we found that UVA led to the upregulation of genes encoding mitochondrial DNA replication proteins and to the downregulation of genes involved genes encoding mtDNA repair factors. Taken together, our findings provide insight into how UVA and UVB differ in their detrimental effects on mtDNA, with UVA impacting mtDNA maintenance and transcription via a ROS-dependent mechanism. Our findings also established the mtDNA CD as a novel potential biomarker for monitoring UVA-induced oxidative stress and photoaging in skin cells in vitro and in vivo.
Longevity Relevance Analysis
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UVA irradiation increases the formation of the common deletion in mitochondrial DNA through a reactive oxygen species-dependent mechanism. This study addresses the molecular mechanisms of photoaging, which is a significant aspect of aging and longevity research, as it explores how UV exposure contributes to cellular dysfunction and mitochondrial damage, potentially impacting lifespan and age-related diseases.
Sebastian Balch, Zala Sekne, Elsa Franco-Echevarría ...
· Telomerase
· MRC Laboratory of Molecular Biology, Cambridge, UK.
· pubmed
Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showed that human telomerase is typically monomeric, containing a single copy of TERT...
Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showed that human telomerase is typically monomeric, containing a single copy of TERT and hTR. Evidence for dimeric complexes exists, although the composition, high-resolution structure, and function remain elusive. Here, we report the cryo-electron microscopy (cryo-EM) structure of a human telomerase dimer bound to telomeric DNA. The structure reveals a 26-subunit assembly and a dimerization interface mediated by the Hinge and ACA box (H/ACA) RNP of telomerase. Premature aging disease mutations map to this interface. Disrupting dimer formation affects RNP assembly, bulk telomerase activity, and telomere maintenance in cells. Our findings address a long-standing enigma surrounding the telomerase dimer and suggest a role for the dimer in telomerase assembly.
Longevity Relevance Analysis
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The paper claims that the dimerization of human telomerase, mediated by the H/ACA RNP, is crucial for its assembly and function in telomere maintenance. This research is relevant as it addresses the fundamental mechanisms of telomerase, which is directly linked to cellular aging and the maintenance of chromosome integrity, thus contributing to our understanding of aging processes.
Hamilton Se-Hwee Oh, Yann Le Guen, Nimrod Rappoport ...
· Nature medicine
· Graduate Program in Stem Cell and Regenerative Medicine, Stanford University, Stanford, CA, USA. [email protected].
· pubmed
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 or...
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17 years' follow-up) of a range of diseases, including heart failure, chronic obstructive pulmonary disease, type 2 diabetes and Alzheimer's disease. Notably, having an especially aged brain posed a risk of Alzheimer's disease (hazard ratio (HR) = 3.1) that was similar to carrying one copy of APOE4, the strongest genetic risk factor for sporadic Alzheimer's disease, whereas a youthful brain (HR = 0.26) provided protection that was similar to carrying two copies of APOE2, independent of APOE genotype. Accrual of aged organs progressively increased mortality risk (2-4 aged organs, HR = 2.3; 5-7 aged organs, HR = 4.5; 8+ aged organs, HR = 8.3), whereas youthful brains and immune systems were uniquely associated with longevity (youthful brain, HR = 0.60 for mortality risk; youthful immune system, HR = 0.58; youthful both, HR = 0.44). Altogether, these findings support the use of plasma proteins for monitoring of organ health and point to the brain and immune systems as key targets for longevity interventions.
Longevity Relevance Analysis
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The paper claims that plasma proteomics can estimate organ age and predict mortality risk, highlighting the brain and immune systems as key targets for longevity interventions. This research is relevant as it addresses biological aging and identifies potential interventions that could influence healthspan and longevity, rather than merely treating age-related diseases.
Ziyu Meng, Yuhao Ma, Wenqi Zhang ...
· Cerebrovascular Circulation
· National Engineering Research Center of Advanced Magnetic Resonance Technologies for Diagnosis and Therapy (NERC-AMRT), School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
· pubmed
Cerebral blood flow (CBF) is a crucial biological marker providing valuable insights into the developmental and aging processes of the central nervous system. A comprehensive understanding of the age- and sex-specific distribution of CBF in healthy populations is essential for di...
Cerebral blood flow (CBF) is a crucial biological marker providing valuable insights into the developmental and aging processes of the central nervous system. A comprehensive understanding of the age- and sex-specific distribution of CBF in healthy populations is essential for distinguishing between pathological changes and those associated with normal aging. This study introduces a collection of age- and sex-specific CBF atlases across the lifespan (7-93 years old), derived from a large data size (N = 1166) obtained from four public and one private datasets. The CBF maps were measured using pseudo-continuous arterial spin labelling (pCASL) MRI and registered to age-specific structural templates derived from corresponding T1-weighted scans. This approach enables a more precise characterization of CBF changes associated with anatomical variations across different age groups. To ensure data reliability, rigorous quality control procedures and extensive validation at both temporal and spatial scales were conducted. These openly accessible atlases serve as a valuable public neuroimaging resource, facilitating the identification of CBF patterns across various stages of development and aging. Additionally, they provide age- and sex-specific health priors, aiding in the detection of abnormal CBF associated with brain disorders throughout the lifespan.
Longevity Relevance Analysis
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The paper claims to provide age- and sex-specific cerebral blood flow atlases that can help distinguish normal aging from pathological changes. This research is relevant as it contributes to understanding the biological markers associated with aging and could aid in identifying age-related changes in brain health.
Fan Wang, Lei Zhou, Yun Zhong ...
· MedComm
· Department of Dermatology, Xiangya Hospital Central South University Changsha China.
· pubmed
N6-methyladenosine (m6A), as the most common RNA modification at the post-transcriptional level, plays a role in various pathophysiological processes. However, its underlying mechanism in skin aging remains enigmatic. Here, we identified that fat mass and obesity-associated prote...
N6-methyladenosine (m6A), as the most common RNA modification at the post-transcriptional level, plays a role in various pathophysiological processes. However, its underlying mechanism in skin aging remains enigmatic. Here, we identified that fat mass and obesity-associated protein (FTO) serves as a protective factor against skin aging. FTO expression is downregulated in aging skin tissues and senescent fibroblasts. Furthermore, the depletion or inhibition of FTO exacerbates dermal fibroblasts senescence and accelerates skin aging. Additionally, RNA-seq combined with MeRIP-seq revealed that lysine acetyltransferase 8 (KAT8) is the downstream target of FTO. FTO deficiency leads to an increase in m6A levels and a decrease in mRNA stability of KAT8 in a m6A-YTHDF2-dependent manner. Notably, our integrated analysis of m6A sequencing and acetylation proteomics links changes in heterochromatin structure with aging. Mechanistically, KAT8 depletion leads to heterochromatin loss and the subsequent aging by acetylating remodeling and spacing factor 1 (RSF1) at K1050. Overall, our finding reveals a pivotal role of FTO-mediated m6A modification in the skin aging by regulating KAT8/RSF1-involved heterochromatin formation. It provides new insights into the mechanisms and strategies for delaying aging and improving healthspan.
Longevity Relevance Analysis
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The paper claims that FTO-mediated m6A modification regulates skin aging through KAT8 and RSF1, linking RNA modifications to heterochromatin dynamics in aging. This research addresses mechanisms underlying skin aging, which is a fundamental aspect of the aging process, rather than merely treating age-related symptoms.
Monteiro-Black, B., Corbally, M.-K., Aleksandrowicz, J. ...
· immunology
· University of Edinburgh
· biorxiv
It is widely accepted that susceptibility to infection increases with age. The reason often invoked is the dysregulation of the immune system, which is both cause and consequence of ageing. However, we do not all age in the same way, and increased susceptibility may not be solely...
It is widely accepted that susceptibility to infection increases with age. The reason often invoked is the dysregulation of the immune system, which is both cause and consequence of ageing. However, we do not all age in the same way, and increased susceptibility may not be solely due to immune dysregulation affecting resistance to infection. There are many possible ways to make a host less tolerant to infection by dysregulating key physiological or metabolic processes. We hypothesised that the increase in susceptibility to infection over age can be linked to both immune ageing and decreased tolerance, and importantly, that it will depend on genotype and sex of the host. We assessed susceptibility to Gram-negative bacterial challenge in both sexes in 22 Drosophila isolines at young and old ages, and leveraged variation between genotypes to investigate how frequently an increase in susceptibility to infection was more associated with a decline in resistance or disease tolerance mechanisms. To achieve this, we assessed pathogen load to report on host immune decline. Strikingly, in most cases, greater infection susceptibility at old age was driven by reduced tolerance, although we also frequently identify cases that suffered bona fide immunosenescence, e.g. impaired resistance. We screened across bacterial pathogens during systemic and oral infections and found sex-specific signatures in survival in young and old individuals, but increased susceptibility with age occurred in both sexes. Pairing infection survival with lifespan data, we find that transcending genotype variation, susceptibility at old age predicts lifespan in males only, regardless of the existence or direction of sex bias in longevity. This work highlights that increased infection susceptibility is an early-arising ageing phenotype that occurs in both sexes, but only predicts lifespan in males, paralleling burgeoning evidence in mammals for male-biased effects of age on infection and its connection with mortality. Our data support a model where infection susceptibility increases with age following the same multiplicative pattern as organismal mortality, with existing failures making new failures more consequential. We propose that the term immunosenescence be used specifically to describe proven dysregulation of immune tissue resistance mechanisms. We argue that to fully understand the drivers of age-related susceptibility to infection, it is essential to consider genotype, sex, and their interaction, as well as the dysregulation of non-immune functions that influence the ability to control pathogens.
Longevity Relevance Analysis
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Increased susceptibility to infection with age is linked to both immune ageing and decreased tolerance, with implications for understanding longevity. The study investigates the mechanisms of infection susceptibility in relation to age and sex, contributing to the understanding of how these factors influence lifespan and aging processes.
Zhang, P., Zheng, L., Qiao, J. ...
· respiratory medicine
· Southern University of Science and Technology
· medrxiv
Background: Leukocyte telomere length (LTL) has been implicated in aging and age-related diseases, including chronic respiratory diseases (CRDs). However, the extent and mechanisms of shared genetic architecture between LTL and respiratory health indicators (such as CRDs and lung...
Background: Leukocyte telomere length (LTL) has been implicated in aging and age-related diseases, including chronic respiratory diseases (CRDs). However, the extent and mechanisms of shared genetic architecture between LTL and respiratory health indicators (such as CRDs and lung function parameters) remain incompletely understood. Methods: We first systematically characterized the genetic correlations and genetic overlaps between LTL and multiple respiratory health indicators. We then performed horizontal pleiotropy analysis by integrating SNP-level functional annotation, gene mapping, and pathway analysis to identify candidate pleiotropic loci, genes, and shared biological pathways. Finally, we assessed the causal relationships among these trait pairs using the latent causal variable (LCV) and MRlap. Results: There was extensive genetic overlap between LTL and respiratory health indicators, regardless of whether these trait pairs had significant genetic associations. We identified 27,885 candidate pleiotropic loci and 82 pleiotropic genes. Notably, five key genes, such as STN1, MPHOSPH9, MTRFR, MAX, and UCKL1, showed significant pleiotropic effects in multiple phenotype pairs and mediated different patterns of genetic associations. Pathway enrichment analysis of these pleiotropic genes highlighted the close association of specific trait pairs with RNA metabolism and telomere maintenance. Finally, vertical pleiotropy analysis revealed negative causal associations of LTL-idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease-LTL. Conclusions: Our findings reinforce the roles of telomere biology and RNA processing in the pathogenesis of chronic lung diseases and support a shared genetic basis for common molecular pathways.
Longevity Relevance Analysis
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The paper identifies extensive genetic overlaps between leukocyte telomere length and chronic respiratory diseases, suggesting shared biological pathways. The focus on telomere biology as a potential root cause related to aging and its implications for chronic diseases makes it relevant to longevity research.
Mengya Feng, Min Li, Jing Lou ...
· Longevity
· Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
· pubmed
It is well-known that physical activity exerts health benefits, yet the potential impacts of early-life regular exercise on later-life health and lifespan remains poorly understood. Here, we demonstrate that 3 months of early-life exercise in mice results in lasting health benefi...
It is well-known that physical activity exerts health benefits, yet the potential impacts of early-life regular exercise on later-life health and lifespan remains poorly understood. Here, we demonstrate that 3 months of early-life exercise in mice results in lasting health benefits, extending healthspan, but not lifespan. C57BL/6J mice underwent swimming exercise from 1 to 4 months of age, followed by detraining for the remainder of their lives. While early-life exercise did not extend the overall lifespan, it significantly improved healthspan in both male and female mice, as evidenced by enhanced systemic metabolism, cardiovascular function, and muscle strength, as well as reduced systemic inflammation and frailty in aged mice. Multiple-organ transcriptome analyses identified enhanced fatty acid metabolism in skeletal muscles as a major feature in aged mice that underwent early-life exercise. These findings reveal the enduring long-term health benefits of early-life exercise, highlighting its pivotal role in improving healthspan.
Longevity Relevance Analysis
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Early-life exercise improves healthspan in mice without extending lifespan. The study addresses the impact of early-life interventions on healthspan, which is a critical aspect of longevity research focused on enhancing quality of life in aging rather than merely extending lifespan.
Amir Ajoolabady, Domenico Pratico, Suhad Bahijri ...
· Experimental & molecular medicine
· National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China.
· pubmed
Cellular senescence is a process in which the cell cycle becomes permanently arrested, thereby inhibiting cell division, proliferation and growth. Various cellular stresses, such as DNA damage, telomere shortening and oxidative stress, can trigger cellular senescence. Physiologic...
Cellular senescence is a process in which the cell cycle becomes permanently arrested, thereby inhibiting cell division, proliferation and growth. Various cellular stresses, such as DNA damage, telomere shortening and oxidative stress, can trigger cellular senescence. Physiologically, cellular senescence contributes to tissue development, repair and critical biological processes such as embryogenesis, whereas, pathologically, it plays a key role in diverse disease subsets. To this end, elucidating the underlying mechanisms and molecular regulation of senescence is crucial. Here, in this Review, we explore recent key findings on cellular senescence in experimental and human disease models, focusing on its molecular mechanisms, regulation and future research directions to advance the field and facilitate therapeutic translation.
Longevity Relevance Analysis
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The paper explores the mechanisms and regulation of cellular senescence, which is crucial for understanding aging processes and potential interventions. Cellular senescence is directly linked to aging and age-related diseases, making this research relevant for addressing the root causes of aging.
Reyhan Westbrook, Vinal Menon, Joy Cagmat ...
· GeroScience
· Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
· pubmed
Chronic inflammatory pathway activation increases with age and is epidemiologically linked to multiple aging-related pathophysiological processes, phenotypes such as physical frailty and sarcopenia and early healthspan declines in aging organisms. Despite this, molecular mechanis...
Chronic inflammatory pathway activation increases with age and is epidemiologically linked to multiple aging-related pathophysiological processes, phenotypes such as physical frailty and sarcopenia and early healthspan declines in aging organisms. Despite this, molecular mechanisms that directly connect chronic inflammation to these conditions remain poorly characterized. We hypothesize that chronic inflammation contributes to the development of age-related phenotypes by increasing the degradation of dietary tryptophan into multiple metabolites with unique physiological properties, called kynurenines, via the 'kynurenine pathway' (KP). To understand the impact of elevated KP metabolites on mammalian healthspan we utilized the quinolinate phosphoribosyltransferase knock-out (QPRT
Longevity Relevance Analysis
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Chronic inflammation drives the degradation of dietary tryptophan into kynurenines, impacting healthspan in aging organisms. The study addresses the molecular mechanisms linking chronic inflammation to age-related phenotypes, which is crucial for understanding and potentially mitigating the root causes of aging.
Pei Wei, Xiaoyan Zhang, Chi Yan ...
· Aging
· Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
· pubmed
Aging is an inherent phenomenon that is highly important in the pathological development of numerous diseases. Aging is a multidimensional phenomenon characterized by the progressive impairment of various cellular structures and organelle functions. The basis of human organ senes...
Aging is an inherent phenomenon that is highly important in the pathological development of numerous diseases. Aging is a multidimensional phenomenon characterized by the progressive impairment of various cellular structures and organelle functions. The basis of human organ senescence is cellular senescence. Currently, with the increase in human life expectancy and the increasing proportion of the elderly population, the economic burden of diseases related to aging is becoming increasingly heavy worldwide, and an in-depth study of the mechanism of cellular aging is urgently needed. Aging, a multifactor-driven biological process, is closely related to mitochondrial dysfunction, which is the core pathological basis of a variety of age-related diseases. This article systematically reviews the molecular pathways by which mitochondrial dysfunction drives aging through multidimensional mechanisms such as metabolic reprogramming, epigenetic regulation, telomere damage, autophagy imbalance, and the senescence-associated secretory phenotype. Metabolic reprogramming promotes tumor progression and exacerbates energy metabolism disorders through abnormal activation of the PI3K/Akt/mTOR signaling pathways. The sirtuin family (such as SIRT1 and SIRT3) maintains mitochondrial homeostasis by regulating PGC-1α, FOXO3 and other targets. Telomere shortening directly inhibits mitochondrial biosynthesis through the p53-PGC-1α axis, leading to oxidative stress accumulation and a decline in organ function. The dual roles of autophagy (removing damaged mitochondria or inducing apoptosis) suggests that its homeostasis is essential for delaying aging. The SASP mediates the inflammatory microenvironment through the cGAS‒STING pathway, which is not only a marker of aging but also a driving force of disease progression. Future studies need to integrate multiomics techniques to analyze the interaction network between mitochondria and other organelles, such as the endoplasmic reticulum and lysosomes, and explore precise intervention strategies targeting sirtuins, AMPK and telomerase. Combined therapies targeting metabolic reprogramming or SASP inhibition are expected to provide new ideas for delaying aging and preventing age-related diseases.
Longevity Relevance Analysis
(4)
Mitochondrial dysfunction drives aging through various molecular pathways and mechanisms. The paper addresses the root causes of aging by exploring mitochondrial dysfunction and its implications for age-related diseases, making it relevant to longevity research.
Joon Hyuk Park, Ki Woong Kim
· Psychiatry investigation
· Department of Psychiatry, Jeju National University Hospital, Jeju, Republic of Korea.
· pubmed
Haenyeo, Korea's traditional female breath-hold divers, represent a unique model for studying brain adaptation to extreme environmental stressors. Diving daily without breathing equipment, they endure hypoxia, hydrostatic pressure, and cold exposure, often well into their senior ...
Haenyeo, Korea's traditional female breath-hold divers, represent a unique model for studying brain adaptation to extreme environmental stressors. Diving daily without breathing equipment, they endure hypoxia, hydrostatic pressure, and cold exposure, often well into their senior years. Research on haenyeo has broader implications for fields such as aging research, space exploration, and underwater medicine. Haenyeo provide an extraordinary lens through which to explore human brain resilience and adaptability. Their experiences demonstrate the brain's capacity for enduring and adapting to extreme physical and cognitive demands over a lifetime. Studying haenyeo offers valuable insights into protecting brain health in extreme environments and aging populations.
Longevity Relevance Analysis
(4)
The paper claims that studying the haenyeo can provide insights into human brain resilience and adaptability to extreme environments. This research is relevant as it explores human adaptations that could inform strategies for promoting brain health and resilience in aging populations.
Jacinta Correia, Promit Sinha Roy, Kaitlyn G Holden ...
· The journals of gerontology. Series A, Biological sciences and medical sciences
· Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA, USA.
· pubmed
Emerging evidence highlights the critical role of cellular metabolism in immune cell activation, development, and function. Peroxisomes, key metabolic organelles, maintain metabolic homeostasis, yet their role in immune cells remains underexplored. While animal studies show age-r...
Emerging evidence highlights the critical role of cellular metabolism in immune cell activation, development, and function. Peroxisomes, key metabolic organelles, maintain metabolic homeostasis, yet their role in immune cells remains underexplored. While animal studies show age-related declines in peroxisome biogenesis, this process is unconfirmed in human aging. We investigated peroxisome biogenesis in human peripheral blood mononuclear cells (PBMCs) and found a significant decline in aged CD19+ B cells compared to CD4+ T cells, CD8+ T cells, and CD14+ monocytes. B cell aging also reduces peroxisomal matrix enzyme import, evidenced by decreased SKL-containing enzymes and mature ACOX1, alongside downregulation of PEX19 and E3 ubiquitin ligases PEX2, PEX10, and PEX12. These findings confirm an evolutionarily conserved and age-related decline in peroxisome biogenesis. Further, our work unveils cell type-specific changes in aging human PBMCs, and provides new insights into peroxisome-mediated immunometabolism and B cell aging.
Longevity Relevance Analysis
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Aging impairs peroxisome biogenesis in human B cells. This study explores the decline in peroxisome biogenesis in aging B cells, contributing to our understanding of cellular mechanisms underlying aging and immune function, which are critical for longevity research.
Perdikis, D., Sleimen-Malkoun, R., Müller, V. ...
· neuroscience
· Charite University Hospital Berlin: Charite Universitatsmedizin Berlin
· biorxiv
Adaptive behavior depends on the brains capacity to vary its activity across multiple spatial and temporal scales. Yet, how distinct facets of this variability evolve from childhood to older adulthood remains poorly understood, limiting mechanistic models of neurocognitive aging....
Adaptive behavior depends on the brains capacity to vary its activity across multiple spatial and temporal scales. Yet, how distinct facets of this variability evolve from childhood to older adulthood remains poorly understood, limiting mechanistic models of neurocognitive aging. Here, we characterize lifespan neural variability using an integrated empirical-computational approach. We analyzed high-density EEG cohort data spanning 111 healthy individuals aged 9-75 years, recorded at rest and during passive and attended auditory oddball stimulation task. We extracted scale-dependent measures of EEG fluctuations amplitude and entropy, together with millisecond-resolved phase-synchrony networks in the 2-20 Hz range. Multi-condition partial least squares decomposition analysis revealed two independent lifespan trajectories. First, slow-frequency power, variance and complexity at longer timescales declined monotonically with age, indicating a progressive dampening of low-frequency fluctuations and large-scale coherence. Second, the temporal organization of phase-synchrony reconfigurations followed an inverted U-trend: young adults exhibited the slowest yet most diverse switching--characterized by low mean but high variance and low kurtosis of jump lengths at 2-6 Hz and the opposite pattern at 8-20 Hz--whereas children and older adults showed faster, more stereotyped dynamics. To mechanistically account for these patterns, we fitted a ten-node phase-oscillator model constrained by the human structural connectome. Only an intermediate, metastable coupling regime reproduced the empirical combination of reduced low-frequency variability and maximally heterogeneous synchrony dynamics observed in young adults, while deviations toward weaker or stronger coupling mimicked the childrens and older adults profiles. Our results demonstrate that development and aging entail changes in the switching dynamics of EEG phase synchronization, by differentially sculpting stationary and transient aspects of neural variability. This establishes time-resolved phase-synchrony metrics as sensitive, mechanistically grounded markers of neurocognitive status across the lifespan.
Longevity Relevance Analysis
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The paper claims that lifespan neural variability changes in brain network switching dynamics across different age groups. This research is relevant as it explores the mechanistic understanding of neurocognitive aging, which is fundamental to addressing the root causes of aging and improving lifespan health.
Valeria Cordone, Teresa Vergara, Stefano Falone ...
· Biology of reproduction
· Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
· pubmed
Recent findings highlight NAD+ as a central regulator of various cellular processes, including energy metabolism, stress response, and aging. The growing evidence of the benefits associated with dietary NAD+ precursors has elevated NAD+ to a promising therapeutic target for addre...
Recent findings highlight NAD+ as a central regulator of various cellular processes, including energy metabolism, stress response, and aging. The growing evidence of the benefits associated with dietary NAD+ precursors has elevated NAD+ to a promising therapeutic target for addressing female infertility. This review aims to evaluate existing literature on the mechanisms governing the availability and utilization of NAD+ in the ovaries and its alterations in female reproductive disorders, with a particular focus on ovarian aging and dysfunction including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Alongside data from in vivo and in vitro studies on various NAD+ boosters, this review incorporates findings from research on genetic mutations, polymorphisms in human and animal populations, and insights from transgenic animal models. The present work emphasizes that NAD+ deficiency is largely driven by a combination of factors, including heightened consumption, impaired utilization efficiency, and diminished biosynthesis or transport. Analysing these aspects, we suggest that the ovary possesses its own unique NAD+ metabolism, but our understanding of the mechanisms governing it is still in its infancy. Key questions remain unanswered, such as how NAD+ and its precursors are transported into oocytes and ovarian cells, their specific preferences for different NAD+ precursors, as well as the specific changes associated with different ovarian dysfunctions. Finally, in this review methods for studying NAD+ metabolism are reported as essential tools to properly investigate the potential of NAD+ boosting therapies for counteracting ovarian aging and dysfunction.
Longevity Relevance Analysis
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NAD+ deficiency is a key factor in ovarian aging and dysfunction, suggesting that boosting NAD+ levels may counteract these issues. The paper addresses the mechanisms of NAD+ in relation to ovarian aging, which is directly linked to the broader understanding of aging processes and potential interventions.
Guo, D., Chen, Y., Wu, Y. ...
· microbiology
· Tsinghua University Shenzhen International Graduate School
· biorxiv
Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of skin microbiome in skin aging phenotypes remains unclear. To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergen...
Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of skin microbiome in skin aging phenotypes remains unclear. To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergent skin aging phenotypes. Genome-scale metabolic models (GEMs) integrated with metabolomic analysis revealed that Stenotrophomonas maltophilia, enriched in the younger group (categorized by AI-predicted age and skin elasticity), utilizes the glutathione cycle to maintain redox homeostasis. Cellular experiments showed its metabolites enhanced GSH synthesis and alleviated oxidative stress-induced skin aging by upregulating key genes in fibroblasts, including GCLM, PGD, SOD2, and NQO1. Additionally, GEMs highlighted its potential anti-aging roles in regulating host metabolic pathways involving betaine, lysolecithin, and porphyrin. In parallel, Acinetobacter guillouiae was found to influence host melanin metabolism by degrading dopamine (DA) and 3-methoxytyramine (3-MT), offering potential therapeutic strategies for mitigating pigmentation. Our findings highlight the dynamic interplay between skin microbiota and the host in aging, offering new insights for designing targeted anti-aging interventions.
Longevity Relevance Analysis
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The paper claims that Stenotrophomonas maltophilia can alleviate oxidative stress-induced skin aging by enhancing glutathione synthesis and regulating key metabolic pathways. This research is relevant as it explores the role of the skin microbiome in aging, potentially addressing root causes of skin aging and offering insights for anti-aging interventions.
Gurcharan Kaur, Tamas Fulop, Arpita Konar ...
· Longevity
· Department of Biotechnology, Guru Nanak Dev University, Amritsar, India. [email protected].
· pubmed
Ageing is associated with neuroimmune shifts from a resting to a hyperactive and inflammatory state, termed 'Neuroinflammageing', attributed to microglial priming, hyperactive astrocytes, cytokine and chemokine release, blood brain barrier leakage, and infiltration of peripheral ...
Ageing is associated with neuroimmune shifts from a resting to a hyperactive and inflammatory state, termed 'Neuroinflammageing', attributed to microglial priming, hyperactive astrocytes, cytokine and chemokine release, blood brain barrier leakage, and infiltration of peripheral immune cells. This special issue of Biogerontology on 'Neuroimmunology in Ageing and Longevity' brings together 11 reviews and original research papers dealing with the complex cross-talk between CNS and peripheral immune cells and molecules in the context of ageing. The articles compiled under this issue further address how understanding neuroimmune pathways may help to identify targets to design interventional regimens for healthy brain ageing and longevity.
Longevity Relevance Analysis
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Understanding neuroimmune pathways may help identify targets for interventions aimed at promoting healthy brain ageing and longevity. The paper addresses the underlying mechanisms of neuroinflammation in ageing, which is crucial for developing strategies to mitigate age-related decline and enhance longevity.
Jinchai Qi, Xuhua Gao, Wanting Ye ...
· Naunyn-Schmiedeberg's archives of pharmacology
· School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
· pubmed
Aging is a degenerative process, and while Rosa roxburghii Tratt has demonstrated notable anti-aging and antioxidant properties, the precise anti-aging effects of its seeds are not yet fully understood. The aim of this study was to employ a blend of in "dry" and "wet" approaches ...
Aging is a degenerative process, and while Rosa roxburghii Tratt has demonstrated notable anti-aging and antioxidant properties, the precise anti-aging effects of its seeds are not yet fully understood. The aim of this study was to employ a blend of in "dry" and "wet" approaches to investigate the anti-aging activity and underlying mechanisms of the polyphenol-rich extract from these seeds, Rosa roxburghii Tratt seed polyphenol extract (RRTSPE). UPLC-Q-Exactive Orbitrap/MS was employed to identify the chemical constituents of RRTSPE, resulting in the identification of 33 chemical components. Subsequent in vitro antioxidant assays demonstrated RRTSPE's moderate antioxidant capacity, and in vivo evaluations using Caenorhabditis elegans (C. elegans) confirmed its ability to extend lifespan, reduce lipofuscin accumulation, and enhance resistance to oxidative and heat stress. Network pharmacology analysis suggests that RRTSPE's anti-aging effects may involve key proteins linked to metabolic and inflammatory diseases. The predictions regarding the anti-aging effects of RRTSPE were further substantiated using mutant C. elegans strains (DR26, VC475, TJ1052, and CB1370), which confirmed the engagement of the insulin/IGF-1 signaling (IIS) pathway in RRTSPE's anti-aging effects. RRTSPE demonstrates its anti-aging effects in C. elegans through a multifaceted approach, which includes scavenging free radicals, diminishing reactive oxygen species (ROS), enhancing DAF-16 nuclear translocation, and modulating IIS pathway-related proteins like SOD-3 and HSP-16.2. It is the synergistic effect of these actions that underpins the broad-spectrum anti-aging potential of RRTSPE. Taken together, this study not only provides a scientific foundation for the utilization of Rosa roxburghii Tratt seeds as a natural anti-aging agent but also paves the way for further research and development in leveraging their potential health benefits.
Longevity Relevance Analysis
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The study claims that Rosa roxburghii Tratt seed polyphenol extract can extend lifespan and enhance stress resistance in C. elegans through mechanisms involving the insulin/IGF-1 signaling pathway. This paper is relevant as it investigates the anti-aging effects of a natural extract and explores its potential mechanisms, contributing to the understanding of longevity and aging processes.
Yumeng Lin, Mengjun Yan, Lili Shen ...
· The journals of gerontology. Series A, Biological sciences and medical sciences
· Health Management Center, Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, China.
· pubmed
As human lifespan extends, the impact of aging on health has become a significant research area, with increasing focus on pulmonary health. The lung, as a complex organ, undergoes various microenvironmental changes during aging, which are crucial for lung function and the develop...
As human lifespan extends, the impact of aging on health has become a significant research area, with increasing focus on pulmonary health. The lung, as a complex organ, undergoes various microenvironmental changes during aging, which are crucial for lung function and the development of related diseases. Aging affects the pulmonary microenvironment in multiple ways, accelerating the decline in lung function. One of the key mechanisms of aging is cellular senescence, which refers to the state in which cells lose their ability to divide and function properly. Cellular senescence leads to a decline in the regenerative capacity of lung cells and may trigger inflammatory responses. Correspondingly, aging also affects the immune system, making the older adults more susceptible to respiratory infections. Moreover, intercellular communication within the pulmonary microenvironment changes during aging, potentially compromising lung structural integrity and function. Understanding these processes is essential for developing new therapeutic strategies to delay lung aging and improve pulmonary health in the older adults. This review focuses on the impact of aging on the pulmonary microenvironment, including changes in cellular senescence, alterations in immune responses, and the involved molecular mechanisms, aiming to provide insights for the diagnosis and treatment of age-related pulmonary diseases.
Longevity Relevance Analysis
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The paper discusses the mechanisms of aging in the pulmonary microenvironment and potential therapeutic strategies to delay lung aging. This research is relevant as it addresses the underlying biological processes of aging and seeks to improve health outcomes in older adults, aligning with the goals of longevity research.
Can Liu, Dongbin Zheng, Rui Zhang ...
· Aging cell
· State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
· pubmed
Aging leads to a gradual decline in muscle function, yet the mechanisms by which different skeletal muscles respond to aging remain unclear. Here, we constructed transcriptional maps of 11 skeletal muscles with extensive transcriptional diversity from young and old mice. Age-rela...
Aging leads to a gradual decline in muscle function, yet the mechanisms by which different skeletal muscles respond to aging remain unclear. Here, we constructed transcriptional maps of 11 skeletal muscles with extensive transcriptional diversity from young and old mice. Age-related changes in gene expression displayed distinct tissue-specific patterns, involving muscle diseases and metabolic processes. Notably, the mitochondrial-enriched soleus muscle exhibited superior resistance to aging compared to other skeletal muscles. Further, we generated a single-nuclei transcriptomic atlas on representative skeletal muscles, analyzing 73,170 nuclei. We found the age-related changes in the cellular composition of different skeletal muscles and the emergence of new cell states in aged mice. Among different types of myonuclei, type II myonuclei showed particular sensitivity to aging, with reduced metabolic activity of IIb myonuclei with age. We also found cell-specific changes occurring across nonmuscle nuclei populations, including adipocytes, fibro-adipogenic progenitors, and immune cells, accelerating muscle aging and associated pathologies. Intercellular communication analysis revealed more intensive intercellular interactions in aged skeletal muscles, particularly between myonuclei and other cell types. Specifically, we validated the regulatory role of the EGF/EGFR axis in age-related inflammatory processes. These findings provide insight into muscle biology and aging and highlight potential therapeutic targets for age-associated muscle disorders.
Longevity Relevance Analysis
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The paper claims that distinct transcriptional changes in skeletal muscles due to aging can reveal potential therapeutic targets for age-associated muscle disorders. This research is relevant as it investigates the underlying mechanisms of aging in skeletal muscles, aiming to understand and potentially mitigate age-related decline in muscle function, which is a significant aspect of longevity research.