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RESEARCH PAPER / 2025-10-13

The Aging Landscape by scRNAseq of Mesenchymal Lineage Cells in Mouse Bone.

Melda Onal, Intawat Nookaew, Ana Resende-Coelho, Olivia Reyes-Castro, Adriana Marques-Carvalho, Landon Gatrell, Alongkorn Kurilung, Alicen James, Aaron Warren, Ha-Neui Kim, Jinhu Xiong, Charles A O'Brien, Maria Almeida

Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. · pubmed

Abstract

A decrease in osteoblast number and bone formation are seminal contributors to age-related osteoporosis. However, the aging-associated molecular mechanisms that impact osteoblast precursors, osteoblasts, osteocytes, and other bone mesenchymal cell types remain unclear. We performed single-cell RNA-sequencing of mesenchymal cells present at the endosteum and periosteum of young and old C57BL/6 mice of both sexes. Osteoblast precursors and osteoblasts from female endosteum exhibited the greatest changes with aging. Transcriptional changes revealed decreased matrix protein production and autophagy, as well as increased senescence, phosphorylation, and hypoxia. Because deficient macroautophagy in osteoblast lineage cells decreases bone formation, we contrasted the transcriptional changes caused by autophagy inactivation in Atg7

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Research summary

The paper claims that aging leads to significant transcriptional changes in osteoblast precursors and osteoblasts, impacting bone formation. This research addresses the molecular mechanisms underlying age-related osteoporosis, which is a critical aspect of aging and longevity.

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