The near term path to verifying the utility of aging clocks is for the research community to accumulate as much data as possible for as many different clocks as possible, and then sift through it in search of correlations, problems, and reliability. Hence one should expect to see a great many studies in the years ahead that are similar to the one noted here. Some early clocks are known to have unexpected quirks in their sensitivity to interventions known to affect aging and incidence of age-related disease, which might make us suspicious of trusting their output when assessing a novel form of therapy aimed at slowing or reversing aspects of aging. Even clocks that are as well exercised as those used here will require some form of validation for the use of a given form of anti-aging therapy before the results can be taken at face value, and that validation will be a slow and costly process.
Osteoporosis is a major age-related musculoskeletal condition, yet chronological age does not fully capture individual risk. Biological age acceleration (BAA), as a biomarker of systemic aging, may offer greater predictive value for osteoporosis and lifespan loss. We analyzed data from 293,224 participants in the UK Biobank cohort who were free of osteoporosis at baseline. BAA was estimated using two validated models – Klemera-Doubal Method Biological Age (KDM-BA) and PhenoAge. Polygenic risk scores (PRS) were used to account for genetic susceptibility. Multivariable Cox models examined associations of BAA and PRS with incident osteoporosis and all-cause mortality.
Over a median follow-up of 8.5 years, 9,780 participants developed osteoporosis. Each one standard deviation (SD) increase in KDM-BA and PhenoAge acceleration was associated with a 22.6% and 19.3% higher risk of osteoporosis, respectively. Participants in the highest tertile of BAA had a 38-43% increased risk compared to those in the lowest tertile. Individuals with both high BAA and high PRS had nearly threefold higher osteoporosis risk, indicating a strong additive effect. Accelerated aging was also linked to a 1.3-1.8-year reduction in life expectancy at age 45, independent of osteoporosis status.
