August 6th, 2026
Questions regarding the relative importance of different mechanisms and dysfunctions to the progression of aging and eventual mortality are hard to answer definitively. Even given a straightforward class of therapies to target one specific mechanism of aging in isolation of all others, such as senolytics to clear lingering senescent cells, one still has to look at a lot of different studies, extrapolate from mice to humans, and the answer is fuzzy. The other sort of fuzzy answer comes from statistical techniques applied to large longitudinal human epidemiological data sets: compare humans who exhibited different levels of the mechanism in question, and see what happened to them over time. That is the approach taken here in the matter of the chronic inflammation as a driver of aging and age-related mortality. As you can see, the answer produced is a sizable range, arguably not all that informative.
Global population aging underscores the urgent need for biomarkers quantifying biological aging trajectories. While DNA methylation-derived pace of aging (DunedinPoAm) measures individual differences, its generalizability across diverse populations and mechanistic links to systemic inflammation remain underexplored. This study aimed to systematically examine the longitudinal associations between the DunedinPoAm and all-cause mortality in a multiethnic cohort, and to quantify the extent to which systemic inflammatory biomarkers mediate these associations using causal mediation analysis.
