Serum and muscle interleukin-15 levels decrease in aging mice: correlation with declines in soluble interleukin-15 receptor alpha expression.
Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15Ralpha) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15Ralpha (sIL-15Ralpha) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Ralpha expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15Ralpha gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15Ralpha in determining body composition in aging mice, as a model for humans.
Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Tacoma,WA 98493, USA. quinnL@u.washington.edu
LeBris S
LS
Quinn
Barbara G
BG
Anderson
Lena
L
Strait-Bodey
Tami
T
Wolden-Hanson
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D001835:Body Weight / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D019409:Interleukin-15 / Q000097:blood* / Q000235:genetics; D053720:Interleukin-15 Receptor alpha Subunit / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009369:Neoplasms / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D012333:RNA, Messenger