Crane Justin D, MacNeil Lauren G, Lally James S, Ford Rebecca J, Bujak Adam L, Brar Ikdip K, Kemp Bruce E, Raha Sandeep, Steinberg Gregory R, Tarnopolsky Mark A
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Aging Cell. 2015 Aug;14(4):625-34. doi: 10.1111/acel.12341. Epub 2015 Apr 22.
Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging.
衰老通常与皮肤结构恶化相关，这会损害其屏障功能、愈合能力及对疾病的易感性。多项证据表明，这些变化很大程度上是由组织线粒体代谢受损所致。虽然运动对健康有诸多益处，但尚无证据表明其会影响皮肤组织或存在内分泌性的肌肉至皮肤信号传导。我们证明，耐力运动可减轻人类和小鼠皮肤与年龄相关的变化，并确定运动诱导的白细胞介素-（IL）15是衰老皮肤中线粒体功能的新型调节因子。我们表明，运动部分通过骨骼肌中的AMP激活蛋白激酶（AMPK，一种新陈代谢的核心调节因子）来控制IL-15的表达，并且消除肌肉中的AMPK会导致皮肤结构恶化。最后，我们证实，每日进行IL-15治疗可模拟运动对小鼠肌肉和皮肤的一些抗衰老作用。因此，我们阐明了运动赋予皮肤健康益处的一种机制，并表明低剂量IL-15治疗可能是减轻皮肤衰老的有益策略。
