The association of physical function and physical performance with DNA methylation clocks in oldest-old living in Singapore - the SG90 cohort

Abstract Deoxyribonucleic acid (DNA) methylation (DNAm) clocks estimate biological age according to DNA methylation. This study investigated the associations between measures of physical function and physical performance and ten DNAm clocks in the oldest-old in Singapore. The SG90 cohort included a subset of community-dwelling oldest-old from the Singapore Chinese Health Study (SCHS) and Singapore Longitudinal Ageing Study (SLAS). Physical function and performance were assessed using Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living (IADL), World Health Organization Disability Assessment Schedule (WHODAS), Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), handgrip strength, normal gait speed, SPPB fast gait speed (FGS), and. DNAm age from peripheral blood mononuclear cells (PBMC) was measured using 18 DNAm clocks, including first generation clocks (PCHorvath1, PCHorvath2, PCHannum, AltumAge, ENCen100+, ENCEN40+, IntrinClock, RetroAgev1 and RetroAgev2) second and third generation clocks (PCPhenoAge, PCGrimAge, GrimAge2, ZhangMRscore, DNAmFitAge and DunedinPACE) and causality-enriched clocks (YingCausAge, YingAdaptAge, YingDamAge). Linear regression was used to analyse associations. The 433 oldest-old individuals had a median age of 88.6 years [87.5; 90.4] and were predominantly Chinese (95.6%) and female (60.3%). Better performance in IADL, WHODAS, SPPB, SPPB FGS and balance were associated with lower GrimAge2 after adjustment for age, sex, and smoking status (pAdj<0.05). GrimAge2 outperformed other DNAm clocks after adjustment for DNAm smoking-pack-years and DNAm-based cell compositions. Better physical function and physical performance were associated with lower DNAm age deviation and pace of ageing. Longitudinal and intervention studies are needed to explore biological mechanisms underlying these observed associations.