To test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural... Show moreTo test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944 to 1945, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life. Show less
Moqri, M.; Herzog, C.; Poganik, J.R.; Ying, K.J.; Justice, J.N.; Belsky, D.W.; ... ; Ferrucci, L. 2024
The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve... Show moreThe search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.Robust validation of biomarkers of aging will be critical to their clinical translation; here, authors review the key challenges and propose recommendations to overcome them. Show less
