Proteomics Analysis Reveals Aging-Related Changes in Bone

Bone mass declines with age, and the anabolic response to mechanical loading weakens. Although much research has focused on gene transcription, the mechanisms behind bone aging and the loss of mechanoresponsiveness at the protein level are still not well understood.

Researchers from Washington University School of Medicine and Washington University in St. Louis, Missouri, Christopher J. Chermside-Scabbo, John T. Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R. Reid Townsend, and Matthew J. Silva, report how they created a novel proteomics approach and performed paired mass spectrometry and RNA-seq analyses on the tibias of young-adult (5-month) and old (22-month) mice.

The researchers present the first estimate of correlation (Spearman ρ = 0.40) between the transcriptome and bone proteome. Although this is in line with results from other tissues, it implies that variation in transcript levels only accounts for a small portion of the variance in protein levels.

Eight of the 71 age-dependent common targets, including the little-studied Asrgl1 and Timp2, were linked to bone mineral density in earlier GWAS. The researchers verified that Asrgl1 and Timp2 exhibited decreased expression in osteoblasts/osteocytes in old bones using complementary RNA in situ hybridization.

They also discovered evidence of decreased TGF-beta signaling, specifically Tgfb2, with aging. Additionally, the researchers found proteomic alterations after mechanical loading, observing that older bone showed fewer loading-induced changes and that bone changed more with age than with loading at the protein level.

Proteomics of Bone Formation in Young-Adult and Old Mice | Aging-US

Video Credit: Aging-US

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Journal reference:

Chermside-Scabbo, C. J., et al. (2024) A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice. Aging. doi.org/10.18632/aging.206131.

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