The Association of Physical Function and Physical Performance With DNA Methylation Clocks in Oldest-Old Living in Singapore—The SG90 Cohort

Jan 27, 2025The journals of gerontology. Series A, Biological sciences and medical sciences

Physical Ability and Performance Linked to Biological Age Markers in Very Old Adults in Singapore

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Abstract

The median age of participants was 88.6 years, with 433 oldest-old individuals predominantly being Chinese and female.

Better performance in daily living activities and physical assessments was associated with lower biological age estimates from the GrimAge2 clock.
Physical function and performance measures, including balance and gait speed, correlated with lower deviations in DNA methylation age.
GrimAge2 showed superior predictive ability compared to other DNA methylation clocks when accounting for smoking and cell composition.
Observations suggest that improved physical performance could be linked to a slower biological aging process.
Further longitudinal and intervention studies are necessary to investigate the biological mechanisms behind these associations.

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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 10 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 analyze 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 < .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 aging. Longitudinal and intervention studies are needed to explore biological mechanisms underlying these observed associations.

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The Association of Physical Function and Physical Performance With DNA Methylation Clocks in Oldest-Old Living in Singapore—The SG90 Cohort

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