title: 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-α, 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.
authors.affiliation: Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. yasumich@sc.itc.keio.ac.jp
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Michiyo
authors.initials: M
authors.lastname: Takayama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000369:Aged, 80 and over; D000375:Aging; D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D009154:Mutation; D009765:Obesity / Q000097:blood; D010641:Phenotype; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha