Epigenetic clocks

Trial registry update: UNKNOWN. No results reported in the supplied registry record.

Researchers trained an epigenetic clock ("Exogenous Skin clock") on 400+ skin samples to measure sun-driven aging, then tested it against two other clocks in 364 participants with skin samples. The exogenous clock showed stronger associations with sun-seeking behavior (rho=0.18, p=0.004) and facial photodamage (rho=0.33, p=0.028) than general epigenetic clocks, and produced older age estimates in sun-exposed versus sun-protected arm skin samples (p<0.001).

This 24-week randomized controlled trial enrolled 136 postmenopausal women (aged 45-60) assigned to control, exercise training, everolimus (5 mg weekly), or combined treatment. The primary outcome was percentage change in bone formation marker P1NP at week 24, with secondary outcomes including bone resorption marker CTX, bone mineral density, bone structure, muscle function, and postural balance. The study does not report the effect sizes or results for any outcome.

This observational study examined whether exercise volume from a 6-month supervised high-intensity interval training program was associated with changes in DNA methylation-based biological aging measures and other physiological markers in adults aged 50-70 years. Participants completed three supervised sessions weekly, with training intensity individually prescribed and monitored. The study assessed multiple biological aging clocks (DNAmFitAge, DNAmPhenoAge, DNAmGrimAge, Hannum Age, DunedinPACE, and others) along with cardiovascular function, aerobic capacity, muscle performance, body composition, metabolic biomarkers, and gut microbiome composition before and after the intervention.

This observational pilot study analyzed DNA methylation epigenetic clocks in blood samples from 14 heart failure patients to assess whether biological age acceleration predicted cardiorespiratory fitness. While biological age showed correlations with fitness measures, chronological age performed equally well, and epigenetic age acceleration was not significantly associated with any fitness parameter. Epigenetic clocks did not add predictive value beyond chronological age alone.

This observational study examined whether the senolytics quercetin and dasatinib affected epigenetic aging rates in healthy individuals over 16 weeks. Participants underwent epigenetic age testing at baseline, the 8-week midpoint, and after 16 weeks. The abstract does not report what effects were actually found.

In 326,873 UK Biobank participants, two measures of biological age acceleration (KDMAgeAccel and PhenoAgeAccel) were associated with increased risk of pancreatic diseases. The highest acceleration group (G4) had 1.7–3.6 times higher hazard ratios across pancreatic outcomes compared to the lowest group (G1), with the strongest associations for chronic pancreatitis (HR 3.551). Circulating lipid biomarkers partially mediated these associations, accounting for 6–9% of the effect.

This cohort study of 399 breast cancer patients from NHANES (1999-2020) examined whether three biological age indicators—calculated from 12 blood-based biomarkers—predicted all-cause mortality over a median 6.67-year follow-up. During this period, 144 deaths occurred. All three measures showed associations with increased mortality: Homeostatic Dysregulation (HR=1.465), Klemera-Doubal Method (HR=1.017), and Phenotypic Age (HR=1.080). Homeostatic Dysregulation performed better for short-term prediction while Phenotypic Age showed better efficacy for longer-term prediction.

This observational study of 1,559 adults aged 50 and older from NHANES (1999-2002) examined the relationship between DNA methylation-based aging clocks and periodontitis using logistic regression. Higher quartiles of PhenoAge and GrimAge2 clocks, and their acceleration measures, were associated with increased odds of periodontitis (odds ratios ranging from 1.96 to 2.80). GrimAge2 showed the highest discriminative ability with an AUC of 0.700.

This systematic review synthesizes evidence on GLP-1 receptor agonists as potential geroprotective agents. Clinical trials showed: SELECT trial found 19% reduction in all-cause mortality (HR 0.81) in obese patients without diabetes; FLOW trial showed 24% reduction in primary kidney composite endpoint (HR 0.76); and a 2025 semaglutide trial demonstrated significant deceleration of three DNA methylation aging clocks (DunedinPACE, PCGrimAge, PhenoAge) over 32 weeks. Mechanistic evidence links benefits to hypothalamic GLP-1 receptor signaling, AMPK/SIRT1 pathways, and microbiome-derived short-chain fatty acids.

A meta-analysis of 29 studies (550,550 female participants) examined associations between reproductive history and DNA methylation clocks, which estimate epigenetic age acceleration. Earlier age at menopause was significantly associated with higher epigenetic age (β=−0.08 years per year earlier for GrimAge), and higher parity was associated with increased epigenetic age (β=0.13 years per delivery for PhenoAge). Age at menarche showed no consistent relationship with epigenetic age across clock types.

This observational study of 168 youth examined whether different types of early life adversity (threat vs. deprivation) were associated with fear responses and accelerated biological aging. Threat-related adversity was associated with impaired discrimination between danger and safety cues during fear conditioning and with greater left amygdala activation to negative stimuli. However, the study found no evidence that fear responses explained the link between threat and accelerated biological aging (advanced puberty or epigenetic age).