title: Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging.
abstract: 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.
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.|Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.|Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Crane
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: MacNeil
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: James S
authors.initials: JS
authors.lastname: Lally
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ford
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Bujak
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ikdip K
authors.initials: IK
authors.lastname: Brar
authors.affiliation: Department of Medicine, St. Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Vic., Australia.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Raha
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Steinberg
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015444:Exercise; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C496843:COX7B protein, human; D019409:Interleukin-15; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human; D003576:Electron Transport Complex IV; D055372:AMP-Activated Protein Kinases
keywords: aging; exercise; metabolism; mitochondria; muscle; skin