Exercise‐stimulated interleukin‐15 is controlled by<scp>AMPK</scp>and regulates skin metabolism and aging

Crane, Justin D.; MacNeil, Lauren; Lally, James; Ford, Rebecca J.; Bujak, Adam L.; Brar, I; Kemp, Bruce E.; Raha, Sandeep; Steinberg, Gregory R.; Tarnopolsky, Mark A.

doi:10.1111/acel.12341

Cited by 146 publications

(143 citation statements)

References 45 publications

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“…These findings make sense since skin and bone tissue are both primarily made up of collagen type I [9, 10]. Furthermore, Crane et al [11] showed that endurance exercise training in elderly sedentary subjects increased reticular dermis collagen content. From a range of publications it is also known that the nutritional status plays an important role in the maintenance of healthy skin [12-22].…”

Section: Discussionmentioning

confidence: 99%

Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters

Braun

Binder

Grosch

et al. 2018

Skin Pharmacol Physiol

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Background: Skin reaction to spaceflight has not really been studied yet, although the skin has a very important barrier function to protect the body and can contribute to a more general understanding of physiology. It is proposed here to make a more thorough investigation of the skin during long-term spaceflight, using noninvasive techniques. Aims: The aim of the present Skin-B study is to investigate the kinetics and range of possible skin modifications during long-duration spaceflights and their recovery. Methods: In order to investigate the effect on skin physiological parameters during spaceflight, measurements were carried out on 6 astronauts with respect to skin hydration, transepidermal water loss/barrier function, and surface evaluation of the living skin in orbit. Additional measured parameters on the ground were skin elasticity, skin density and thickness, as well as microcirculation. Results: Data from the Skin-B subjects (n = 6) contradict the results obtained in the previous pilot study SkinCare (n = 1 subject). In the present study, no deterioration of the skin was found but rather an improvement in skin hydration and skin barrier function, and no changes or improvement in the appearance of the skin surface. Furthermore, the skin density and skin thickness as well as skin elasticity values were unchanged from pre-flight values. Conclusion: In conclusion, we found that spaceflight under present conditions has no negative impact on skin physiological parameters.

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Section: Discussionmentioning

confidence: 99%

Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters

Braun

Binder

Grosch

et al. 2018

Skin Pharmacol Physiol

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“…IL15 and IL15RA levels are elevated acutely during low-grade inflammation induced by exercise[8–12], but also chronically in pathological conditions such as rheumatoid arthritis, particularly in the synovial fluid[7]. IL15 SNPs correlate with bone mineral density and cortical bone volume in humans[17,45].…”

Section: Discussionmentioning

confidence: 99%

“…IL15 is a widely expressed pro-inflammatory cytokine and also functions as a myokine that is secreted from muscle in response to exercise[8–12]. Elevated IL15 receptor alpha (IL15RA) levels are found in the synovial fluid of patients affected by rheumatoid arthritis and other chronic inflammatory diseases that are associated with bone loss[7,13].…”

Section: Introductionmentioning

confidence: 99%

IL15RA is required for osteoblast function and bone mineralization

Loro

Ramaswamy

Chandra

et al. 2017

Bone

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Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra−/−) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function. We show that lack of IL15RA decreased bone mineralization in vivo and in isolated primary osteogenic cultures, suggesting a cell-autonomous effect. Il15ra−/− osteogenic cultures also had reduced Rankl/Opg mRNA ratio, indicating defective osteoblast/osteoclast coupling. We analyzed the transcriptome of primary pre-osteoblasts from normal and Il15ra−/− mice and identified 1150 genes that were differentially expressed at a FDR of 5%. Of these, 844 transcripts were upregulated and 306 were downregulated in Il15ra−/− cells. The largest functional clusters, highlighted using DAVID analysis, were related to metabolism, immune response, bone mineralization and morphogenesis. The transcriptome analysis was validated by qPCR of some of the most significant hits. Using bioinformatic approaches, we identified candidate genes, including Cd200 and Enpp1, that could contribute to the reduced mineralization. Silencing Il15ra using shRNA in the calvarial osteoblast MC3T3-E1 cell line decreased ENPP1 activity. Taken together, these data support that IL15RA plays a cell-autonomous role in osteoblast function and bone mineralization.

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“…Crane and colleagues demonstrated that exercise attenuated skin changes associated with aging in both humans and mice [49]. Physical activity induces IL15 release from skeletal muscles through the AMPK pathway[49] and IL15 modulates mitochondrial function in skin. Interestingly, IL15 injections into mice mimic anti-aging effects of exercise both in muscle and skin.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, IL15 injections into mice mimic anti-aging effects of exercise both in muscle and skin. Overall, this pioneering study describes a mechanism that explains, at the molecular level, how physical activity attenuates skin aging through IL15-dependent processes[49]. …”

Section: Introductionmentioning

confidence: 99%

Muscle as a paracrine and endocrine organ

Giudice

Taylor

2017

Current Opinion in Pharmacology

269

186

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Skeletal muscle cells are highly abundant and metabolically active and are known to ‘communicate’ their energy demands to other organs through active secretion. Muscle-derived secretory proteins include a variety of cytokines and peptides collectively referred to as “myokines” that exert auto-, para- or endocrine effects. Analyses of the skeletal muscle secretome revealed that numerous myokines are secreted in response to contraction or strength training, and that these factors not only regulate energy demand but also contribute to the broad beneficial effects of exercise on cardiovascular, metabolic, and mental health. Herein we review recent studies on the myokines that regulate muscle function and those that mediate cross talk between skeletal muscle and other organs including adipose tissue, liver, pancreas, the cardiovascular system, brain, bones, and skin.

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Exercise‐stimulated interleukin‐15 is controlled byAMPKand regulates skin metabolism and aging

Cited by 146 publications

References 45 publications

Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters

Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters

IL15RA is required for osteoblast function and bone mineralization

Muscle as a paracrine and endocrine organ

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