Exercise‐stimulated interleukin‐15 is controlled by AMPK and regulates skin metabolism and aging
Open accessAbstract
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.
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Most studies in both healthy and obese adults have found increased circulating IL-15 immediately following acute bouts of aerobic exercise (e.g., running or cycling at 55-75% of age-predicted maximum heart rate for 30-120 min).
“Most of the studies in both healthy and obese adults have found increased circulating IL-15 immediately following acute bouts of aerobic exercise (e.g., running or cycling at 55–75% of age-predicted maximum heart rate for 30–120 min) [128,129,130].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [129]
The Discussion (page unavailable) reports a transient rise in circulating IL-15 immediately after exercise in this study and says some, but not all, earlier human studies found an increase. The Experimental procedures describe an approximately 45-minute acute cycling bout, but the 65–75% HRmax protocol belongs to a separate training intervention. Our copy does not establish that most studies found this result in both healthy and obese adults, or support the stated 30–120-minute range. (LLM, conf=0.88)
Experimental — accuracy not yet measuredExercise retards skin aging via a mechanism that involves muscle-derived IL-15.
“The study supports the idea that exercise retards skin aging via a mechanism that involves muscle-derived IL-15.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [200]
Endurance exercise improves age-associated skin changes in both mice and humans.
“Tarnopolsky and colleagues (200) demonstrated that endurance exercise improves age-associated skin changes in both mice and humans.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [200]
IL-15 injections mimic some of the anti-aging effects of exercise on murine skin.
“IL-15 injections mimic some of the anti-aging effects of exercise on murine skin.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [200]
Exercise regulates muscular IL-15 expression via skeletal muscle AMPK.
“They showed that exercise regulates muscular IL-15 expression via skeletal muscle AMPK.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [200]
Elimination of muscle AMPK leads to a weakening of skin structure.
“Elimination of muscle AMPK led to a weakening of skin structure, whereas IL-15 injections mimic some of the anti-aging effects of exercise on murine skin.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [200]
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- Authors
- Crane, J. D., MacNeil, L. G., Lally, J. S., Ford, R. J., Bujak, A. L., Brar, I. K., Kemp, B. E., Raha, S., Steinberg, G. R., & Tarnopolsky, M. A.
- Affiliations
- McMaster University (CA)
- The University of Melbourne (AU)
- Corresponding author
- Tarnopolsky, Mark A.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2015-04-22
- Volume
- 14
- Issue
- 4
- Pages
- 625-634
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC4531076
- OpenAlex
- W2044172090
- Cited by
- 179
- References
- 46
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 30 · 2023: 17 · 2022: 22 · 2021: 17 · 2020: 16 · 2019: 11 · 2018: 10 · 2017: 14 · 2016: 7 · 2015: 5
- FWCI
- 13.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Aging Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Research Bank (Australian Catholic University) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research (119555)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- physical activity, IL-15, AMPK, skin aging, skin metabolism, mitochondrial function, endurance exercise, skeletal muscle, skin barrier function
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adult, Aged, Aged, 80 and over, Aging, Animals, Electron Transport Complex IV, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Middle Aged, Mitochondria, NADH Dehydrogenase, Physical Conditioning, Animal, RNA, Messenger, Skin, Transcription Factors, Signal Transduction, Exercise, Muscle, Skeletal, Interleukin-15, Mice, AMP-Activated Protein Kinases
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