Genetic influence on exercise-induced changes in physical function among mobility-limited older adults

Abstract

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors.

Keywords: ACE gene; aging; disability; exercise; genetics.

Fig. 1.

Distribution of changes in performance. Change in gait speed (top) and short physical performance battery (SPPB) performance (bottom) among participants in the physical activity (left) and health education (right) intervention groups. Data for gait speed indicate individual responses to the interventions, while SPPB data reflect the proportion of individuals with a respective change in SPPB score following treatment.

Fig. 2.

Change in function by genotype and treatment. Change in 400 m usual-paced gait speed and SPPB score among Caucasian participants by ACE I/D genotype and randomized treatment group. Data adjusted for clinic site, body mass index, age, sex, baseline level of the outcome, use of either angiotensin receptor blockers (ARBs) or ACE inhibitors and comorbidity. Columns indicate adjusted mean, bars indicate SE. Numbers within columns indicate sample size.

Fig. 3.

Influence of exercise on function by genotype. Effects of the LIFE-P exercise program on 400 m usual-paced gait speed and SPPB score by ACE I/D genotype among Caucasian participants. Data expressed as change among participants in the exercise group minus mean change in the control group from baseline to 12 mo. Columns indicate adjusted mean, bars indicate SE.

Fig. 4.

Clinically significant changes in gait speed. Proportion of study participants obtaining clinically significant benefits in usual-paced gait speed following 12 mo of exercise, as measured during the 400 m walk test. Data are dichotomized by persons with (ID/DD) and without (II) at least 1 copy of the D allele and depict proportional changes in both the exercise [physical activity (PA)] and health education [successful aging (SA)] intervention groups. The chosen clinically significant change was 0.05 m/s as established in the literature (33, 47). *P < 0.05 between intervention arms.

Fig. 5.

Clinically significant changes in SPPB score. Proportion of study participants obtaining clinically significant benefits in lower extremity function following 12 mo of exercise, based on changes in SPPB score. Data are dichotomized by persons with (ID/DD) and without (II) at least 1 copy of the D allele and depict proportional changes in both the exercise (PA) and health education (SA) intervention groups. The chosen clinically significant change was 1 point as established in the literature (33, 47). *P < 0.05 between intervention arms.