In a cohort of 861 adults followed from age 70 to 89, the GrimAge2 epigenetic clock was the single strongest correlate of all-cause mortality, while leukocyte telomere attrition showed no significant relationship. Four measures — white matter volume, total brain volume, walking time, and general cognitive function — carried the most independent predictive power, together explaining 19% of mortality variance, with 17 additional markers adding only 4%. GDF15, a protein linked to cellular senescence, ranked second only to GrimAge2 among individual markers.
Key Points
- GrimAge2 outperformed all other biomarkers for all-cause mortality prediction
- Four markers explain 19% of mortality variance; others add little
- Leukocyte telomere length showed no significant mortality association
Longevity Analysis
Organ-level aging proceeds largely independently — an aged liver predicts little about the pancreas, heart, or immune compartment — which argues against any single composite number as a sufficient readout of risk. Lung capacity, walking time, and brain volume outperformed several organ-specific molecular clocks, confirming that functional measures capture mortality-relevant decline that proteomics alone misses. For practical tracking, a small, non-redundant panel combining gait, cognition, structural brain imaging, and GDF15 delivers most of the available signal, and serial measurement over years matters more than breadth of any single assessment.
Original published by LifeSpan.io, by Josh Conway.