Adipokines and Aging

Abstract

Dysregulation of adipose tissue-derived bioactive molecules, termed adipokines, is recognized as common ground for insulin resistance and metabolic syndrome associated with obesity. However, adipokine dysregulation is paradoxically associated with lipodystrophy and lipoatrophy with aging. In familial partial lipodystrophic syndromes and Hutchinson-Gilford progeria syndrome, both of which are caused by mutations in the LMNA gene, loss of adipose tissue is associated with adipokine dysregulation, insulin resistance, and atherosclerosis, suggesting a critical role of adipose tissue function in controlling whole body energy metabolism, age-related pathologies, and longevity. Centenarians, a model of healthy aging and longevity, are reported to exhibit preserved insulin sensitivity as well as favorable adipokine profiles, particularly high levels of circulating adiponectin. Furthermore, adipose tissue dysfunction indicated by dysregulation of leptin, tumor necrosis factor-, and adiponectin is associated with poor prognosis in centenarians. In contrast to results obtained for obesity, adipokine dysregulation in centenarians is associated with very low leptin levels, suggesting that age-related lipoatrophy is the major factor for adipose tissue dysfunction at an advanced age. These observations suggest that adipose tissue excess as well as its aging is implicated in the regulation of adipokines, insulin sensitivity, and lifespan in humans.J Atheroscler Thromb, 2011; 18:545-550.

Effects of Aging on Visceral and Subcutaneous Fat Areas and on Homeostasis Model Assessment of Insulin Resistance and Insulin Secretion Capacity in a Comprehensive Health Checkup

“…In human studies, ADPN is reportedly related to metabolic abnormalities 16) and to atherogenic lipoprotein profile 23) . Arai, et al also reported that the centenarians are characterized to be more sensitive (less resistant) to insulin, have high blood ADPN levels, and be less likely to have DM and/or MetS 24) . Although the present study included a small number of participants whose HMW-ADPN levels were measured, serum HMW-ADPN level showed strong negative correlation with HOMA-IR.…”

Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels

“…Moreover, serum levels of total adiponectin, as well as its high molecular weight and middle molecular weight isoforms, were significantly higher in octogenarians than in corresponding middle-aged control groups [14]. Finally, dysregulation of leptin, adiponectin, and TNF-a was found to be a strong marker of poor prognosis in centenarians, independent of conventional risk factors [15].…”

Circulating Adiponectin Levels and their Associated Factors in Young Lean Healthy Japanese Women

“…In this specified study population, we successfully eliminated the influence of age, and even that of adiposity, on adiponectin levels. Although adiponectin levels are reported to be associated with various health disorders [26][27][28][29][30][31][32] , it has been pointed out that their levels vary not only among ethnic groups [33][34][35] but also age groups 10,16) . It seems of clinical importance to evaluate their distribution with respect to each age group of a specific ethnic population.…”