Adipokines and Aging: Findings From Centenarians and the Very Old

Abstract

Adipose tissue, which was once considered as a simple energy storage depot, is now recognized as an active endocrine organ that regulates the whole-body energy homeostasis by secreting hundreds of bioactive substances termed adipokines. Dysregulation of adipokines is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. Previous studies have demonstrated that preserved insulin sensitivity and low prevalence of diabetes are the metabolic peculiarities of centenarians, suggesting the possible role of adipokine homeostasis in healthy longevity. Among the numerous adipokines, adiponectin is regarded as unique and salutary, showing negative correlations with several age- and obesity-related metabolic disturbances and a positive correlation with longevity and insulin sensitivity among centenarians. However, large-scale epidemiological studies have implied the opposite aspect of this adipokine as a prognostic factor for all-cause and cardiovascular mortality in patients with heart failure or kidney disease. In this review, the clinical significance of adiponectin was comparatively addressed in centenarians and the very old, in terms of frailty, cardiovascular risk, and mortality.

Keywords: adipokines; adiponectin; centenarian; frailty; longevity.

Figure 1

Hypothetical roles of adiponectin in centenarians. Based on paradoxical evidence regarding the association between adiponectin and health outcomes, we propose two hypothetical roles of adiponectin in centenarians. Adiponectin is a salutary adipokine that is present at high levels in healthy and lean individuals, e.g., centenarians. High adiponectin levels are associated with low insulin levels and low HOMA-IR, and a favorable lipid profile, which is consequently associated with a low risk of coronary artery disease and type 2 diabetes. In contrast, in patients with catabolic states, such as chronic heart failure and sarcopenia, adiponectin is upregulated as a part of compensatory mechanisms against inflammation and oxidative stress in relevant organs. Once the compensation fails, in case of adiponectin resistance, high adiponectin levels predict high mortality in advanced stage of disease or aging.