Abstract
AIM: Alpha-actinin 3 (ACTN3) is associated with diminished physical function and muscle mass in older individuals. However, the effects of lifestyle on this relationship remain unclear. This study explored whether the association between ACTN3 polymorphisms and physical function and body composition varied based on exercise and dietary habits. METHODS: A longitudinal analysis of 197 community-dwelling individuals aged 60 years and older (mean age 72.5 ± 5.9 years, 60.9% women) in the Tarumizu study provided data on ACTN3 gene polymorphisms, with surveys completed in 2019 and 2022 (mean follow-up 1156 ± 80.0 days). Physical performance (grip strength, walking speed) and body composition (body weight, appendicular skeletal muscle mass [ASMM], and fat mass) were assessed. Genetic polymorphisms were analyzed in oral mucosa samples and categorized into type R allele carriers and type XX alleles (homozygous for minor alleles). Median values determined exercise habits (≤4 days/week or ≥5 days/week) and dietary habits based on high-protein-food frequency scores. RESULTS: The proportion of type XX genetic polymorphism was 26.4%. Two-way repeated-measures analysis of covariance showed a significant interaction between genetic polymorphism and time for ASMM (F = 10.552, P = 0.002) in the ≤4 days/week exercise habits group. Significant interactions were observed in grip strength (F = 7.013, P = 0.009) and ASMM (F = 5.347, P = 0.023) for the ≤11 score high-protein-intake group. CONCLUSIONS: This association may contribute to accelerated age-related changes in physical performance and body composition, particularly among individuals with type XX genetic polymorphism who have low exercise habits and a limited intake of high-protein foods. Geriatr Gerontol Int 2025; 25: 173-181.