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This study used genetic data from UK Biobank and single-cell analysis to demonstrate a bidirectional relationship between aging and osteoporosis, where each condition influences the other. The researchers identified macrophages as critical mediators of this relationship, finding that macrophage percentages in bone marrow decrease with age. Two key molecular regulators were identified: TGFB1 and a novel gene HNRNPUL1, which influence macrophage differentiation and function in age-related bone loss.
Why it matters
Understanding the cellular and molecular mechanisms linking aging to osteoporosis could lead to new therapeutic targets for preventing age-related bone loss. The identification of macrophages and specific genetic regulators provides potential pathways for developing interventions that address both aging processes and bone health simultaneously.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Osteoporosis is a highly prevalent age-related disorder, and accumulating evidence suggests that it does not arise in isolation but is intrinsically linked to the aging process. Here, we employed integrative methods to systematically identify the relationship between aging and osteoporosis, and uncover the critical cell types and molecular regulators that mediate this association. Observational analysis of phenotypic data from UK Biobank and Mendelian Randomization analysis of summary-level statistics revealed that aging and osteoporosis are interrelated, acting as both causes and effects of each other. We identified macrophages as the key cell types mediating this association by integration of GWAS data with a comprehensively assembled single-cell transcriptomic atlas of bone remodeling. And the percentage of macrophages from bone marrow decreases with age. Additionally, shared genetic tools and weight co-expression network analysis were employed to uncover novel molecular regulators underlying this crosstalk. We identified TGFB1 and a novel gene, HNRNPUL1, as key regulators that influence macrophages differentiation and function. In conclusion, our study provides observational and genetic evidence for a bidirectional relationship between aging and osteoporosis and unveils a macrophage-centric mechanism regulated by TGFB1 and HNRNPUL1, offering new insights for age-related bone loss.