Longevity Papers

Molecular mechanisms linking loss of TDP-43 function to amyotrophic lateral sclerosis/frontotemporal dementia-related genes.

Yuka Koike · Amyotrophic Lateral Sclerosis · Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Japan. Electronic address: [email protected]. · pubmed

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43). TDP-43 plays a key role in regulating the splicing of numerous genes, including TARDBP. This review aim...

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are characterized by nuclear depletion and cytoplasmic aggregation of TAR DNA-binding protein-43 (TDP-43). TDP-43 plays a key role in regulating the splicing of numerous genes, including TARDBP. This review aims to delineate two aspects of ALS/FTD pathogenesis associated with TDP-43 function. First, we described novel mechanistic insights into the splicing of UNC13A, a TDP-43 target gene. Single nucleotide polymorphisms (SNPs) in UNC13A are the most common risk factors for ALS/FTD. We found that TDP-43 represses "cryptic exon" inclusion during UNC13A RNA splicing. A risk-associated SNP in this exon results in increased RNA levels of UNC13A retaining the cryptic exon. Second, we described the perturbation of the TDP-43 autoregulatory mechanism caused by age-related DNA demethylation. Aging is a major risk factor for sporadic ALS/FTD. Typically, TDP-43 levels are regulated via alternative splicing of TARDBP mRNA. This review focused on that TARDBP methylation is altered by aging, thereby disrupting TDP-43 autoregulation. It was found that demethylation reduces the efficiency of alternative splicing and increases TARDBP mRNA levels. Moreover, we demonstrated that, with aging, this region is demethylated in the human motor cortex and is associated with the early onset of ALS.

Longevity Relevance Analysis (4)

The paper discusses the molecular mechanisms linking TDP-43 function to ALS and FTD, with a focus on age-related changes that affect TDP-43 regulation. This connection to aging and the exploration of how age-related DNA demethylation impacts TDP-43 autoregulation are relevant to longevity research. However, while the findings contribute to understanding the mechanisms involved, they do not present a significant breakthrough or novel therapeutic approach that addresses the root causes of aging, thus limiting their overall impact.

Nogo-B Silencing Expedites the Senescence of Platelet-Derived Growth Factor-BB-Induced Human Hepatic Stellate Cells Via Autophagy.

Lili Gao, Yingjie Zhuang, Zhengyi Liu · Hepatic Stellate Cells · Department of Gastroenterology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, West Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China. [email protected]. · pubmed

Liver fibrosis is a severe liver pathology in response to chronic or iterative liver injury. Senescence has emerged as a protective mechanism against liver fibrosis. Nogo-B has been well established as a significant contributor to liver fibrosis. Nonetheless, researches regarding...

Liver fibrosis is a severe liver pathology in response to chronic or iterative liver injury. Senescence has emerged as a protective mechanism against liver fibrosis. Nogo-B has been well established as a significant contributor to liver fibrosis. Nonetheless, researches regarding the role of Nogo-B in cell senescence during liver fibrosis are few. In platelet-derived growth factor-BB (PDGF-BB)-treated human hepatic stellate cell line LX-2, cell proliferation was assayed by CCK-8 method. Western blotting estimated the expression of Nogo-B and fibrosis markers. After Nogo-B was silenced in LX-2 cells pretreated by an autophagy activator Rapamycin and PDGF-BB, CCK-8 method was used to assess cell proliferation. Fibrosis was measured by western blotting and immunofluorescence. Cell cycle was subjected to flow cytometry analysis and cell senescence was evaluated by SA-β-gal staining. Immunofluorescence staining assessed autophagy. Nogo-B was elevated in PDGF-BB-exposed LX-2 cells. Nogo-B silencing suppressed the proliferation, fibrosis, and autophagy while induced cell cycle arrest and senescence of LX-2 cells. Additionally, pretreatment with Rapamycin partially restored the effects of Nogo-B knockdown on the autophagy, proliferation, fibrosis, cell cycle, and senescence of LX-2 cells upon exposure to PDGF-BB. Collectively, inactivation of autophagy mediated by Nogo-B deficiency might elicit protective activities against the development of liver fibrosis.

Longevity Relevance Analysis (3)

Silencing Nogo-B in hepatic stellate cells induces senescence and inhibits fibrosis through autophagy modulation. The study addresses mechanisms of cellular senescence and fibrosis, which are relevant to aging and age-related liver diseases.

A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

Julia S Oliveira, Jessica A da Silva, Brenda V M de Freitas ... · Diet, Mediterranean · Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. · pubmed

Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging.

Longevity Relevance Analysis (3)

The paper claims that the Mediterranean diet improves glycation markers in both healthy individuals and those with chronic diseases. The Mediterranean diet is associated with cardiometabolic health, which is relevant to aging and age-related diseases, but the findings are more about dietary effects rather than addressing the root causes of aging.

Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging.

Siyi Zhou, Zeming Li, Xinzhu Li ... · Hair Follicle · Key Laboratory of Biorheological Science and Technology of Ministry of Education & 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address: [email protected]. · pubmed

Tissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vesse...

Tissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions.

Longevity Relevance Analysis (3)

The paper claims that the interaction between endothelial cells and dermal papilla is crucial for hair regeneration and angiogenesis during aging. This research is relevant as it explores the mechanisms underlying aging-related changes in hair follicles and blood vessels, potentially addressing root causes of age-related degeneration.

Pace of Aging in older adults matters for healthspan and lifespan updated v2

Balachandran, A., Pei, H., Shi, Y. ... · epidemiology · Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA · medrxiv

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal ...

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal care and nutrition, from those caused by ongoing changes in peoples bodies due to aging. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in data from the US Health and Retirement Study and English Longitudinal Study of Aging (N=21,463), integrates longitudinal data on blood biomarkers, physical measurements, and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability, and mortality. Pace of Aging can advance the population science of healthy longevity.

Longevity Relevance Analysis (5)

The paper addresses the pace of aging and its implications for healthspan and lifespan, which are central themes in longevity research. By introducing an adapted Pace of Aging method and demonstrating its associations with morbidity, disability, and mortality, the study contributes valuable insights into the quantification of aging processes. However, while the findings are important, they appear to be more of an incremental advance rather than a groundbreaking discovery, hence the moderate impact score.

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases.

Yuchen He, Yishu Fan, Xenab Ahmadpoor ... · Lysosomes · Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. · pubmed

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, l...

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

Longevity Relevance Analysis (4)

The paper discusses lysosomal quality control (LQC) and its association with aging, identifying it as a mechanism that could be targeted for therapeutic strategies against aging and age-related diseases. This focus on LQC as a potential root cause of aging aligns with longevity research. However, while the review summarizes existing knowledge and proposes future research avenues, it does not present novel experimental findings or significant breakthroughs, limiting its overall impact in the field.

Advanced Glycation End Products and Health: A Systematic Review.

Jianming Zhu, Ziming Wang, Chunyan Lv ... · Glycation End Products, Advanced · School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, 541004, China. · pubmed

Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to t...

Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to the accelerated pace of modern life. The accumulation of AGEs is primarily attributed to their inherent difficulty in metabolism, which makes them promising biomarkers for chronic disease detection. This review aims to provide a comprehensive overview of the recent advancements and findings in AGE research. The discussion is divided into two main sections: endogenous AGEs (formed within the body) and exogenous AGEs (derived from external sources). Various aspects of AGEs are subsequently summarized, including their production pathways, pathogenic mechanisms, and detection methods. Moreover, this review delves into the future research prospects concerning AGEs. Overall, this comprehensive review underscores the importance of AGEs in the detection of chronic diseases and provides a thorough understanding of their significance. It emphasizes the necessity for further research endeavors to deepen our comprehension of AGEs and their implications for human health.

Longevity Relevance Analysis (3)

The paper discusses advanced glycation end products (AGEs) and their association with chronic diseases, which is relevant to aging and age-related health issues. However, it primarily focuses on the detection and understanding of AGEs rather than addressing the root causes of aging or proposing solutions for lifespan extension. The findings contribute to the existing knowledge but do not present significant advancements that would have a major impact on the field of longevity research.