Background: Serum adiponectin levels are associated with frailty and cardiovascular diseases. Longitudinal changes in adiponectin levels might enhance our understanding of age-related conditions and diseases. Aims: This prospective observational study aimed to: (1) elucidate age-related changes in high-molecular-weight (HMW) adiponectin levels
and (2) identify variables predictive of elevated HMW adiponectin levels and the association with well-known adiponectin single-nucleotide polymorphisms (SNPs) in healthy, elderly Japanese participants. Methods: Healthy elderly volunteers (n = 196
55 men and 141 women
median age 72.0 years
range 69.0–75.0 years) underwent anthropometric and physical function measurements, as well as laboratory tests at baseline and the 5-year follow-up. Results: HMW adiponectin levels were significantly higher in women than in men (8.4, 5.3–11.9 vs. 5.7, 3.1–9.0 μg/mL
p &lt
0.001) at baseline and decreased significantly at follow-up in women (7.7, 4.8–11.2 μg/mL
p &lt
0.001), but not in men. In the multiple regression analysis, high-density lipoprotein cholesterol levels and body weight were independent predictors of HMW adiponectin levels. The rate of change in HMW adiponectin levels was inversely correlated with the rates of change in body weight, body mass index, and knee leg extension strengths, and positively correlated with rates of change in high-density lipoprotein cholesterol and one-leg standing time. There were no significant differences in HMW adiponectin levels among SNPs. Discussion: Decreasing HMW adiponectin levels might lead to an increased risk of cardiovascular diseases in elderly women. Conclusion: HMW adiponectin levels significantly decreased over a 5-year period in community-dwelling elderly Japanese women.