Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
J Atheroscler Thromb. 2011;18(7):545-50. doi: 10.5551/jat.7039. Epub 2011 May 7.
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.
脂肪组织来源的生物活性分子（称为脂肪因子）的失调被认为是与肥胖相关的胰岛素抵抗和代谢综合征的共同基础。然而，脂肪因子失调与衰老时的脂肪营养不良和脂肪减少是矛盾的。在家族性部分脂肪营养不良综合征和 Hutchinson-Gilford 早老症中，这两种疾病都是由 LMNA 基因突变引起的，脂肪组织的丧失与脂肪因子失调、胰岛素抵抗和动脉粥样硬化有关，这表明脂肪组织功能在控制全身能量代谢、与年龄相关的病理和长寿方面起着关键作用。作为健康衰老和长寿的模型，百岁老人被报道表现出胰岛素敏感性的保留以及有利的脂肪因子谱，特别是循环脂联素水平较高。此外，脂肪组织功能障碍表现为瘦素、肿瘤坏死因子-α和脂联素的失调，与百岁老人的预后不良有关。与肥胖的结果相反，百岁老人的脂肪因子失调与极低的瘦素水平相关，表明与年龄相关的脂肪减少是老年时脂肪组织功能障碍的主要因素。这些观察结果表明，脂肪组织过剩及其衰老与人类脂肪因子、胰岛素敏感性和寿命的调节有关。
