Aging is associated with impaired recovery of muscle mass and function following disuse. The cellular and molecular mechanisms underlying age-related impairments in recovery from disuse are still not fully understood. Prior work in aging has suggested that elevated (COX2)-mediated prostaglandins have been linked to increased markers of cellular senescence, which can further impair tissue regeneration. We hypothesized that excessive COX2 activity during recovery regulates cellular senescence and contributes to poor muscle regrowth in aged mice. To test this, aged male mice (26mo, n=7-12) underwent 14 days of hindlimb unloading (HU) followed by 7 days of reloading. Mice received intraperitoneal injections of saline, low-(30mg/kg/day) or high-dose (60mg/kg/day) ibuprofen on the first two days of reloading. Low dose ibuprofen significantly improved muscle function, characterized by increased grip strength (P< 0.0001) and ex-vivo contractile function (P=0.0451). The low dose also showed a significant decrease in, senescence cells (yH2AX P=0.0380, SA-b-gal P= 0.0124) and fibrosis (P=0.0068) in the gastrocnemius muscle. Across both dosing levels, ibuprofen significantly reduced the expression of key prostaglandin-signaling genes, Ptges and Ptger1 (p < 0.05). Relative to saline, low-dose ibuprofen significantly reduced the expression of senescence markers (p53, p16; p < 0.05) and key SASP mediators (PAI-1, Igfbp4, IL-6, IFN-γ; p < 0.05), indicating attenuation of the senescence burden. These findings suggest a mechanistic link between prostaglandin signaling and cellular senescence in aging muscle and support the therapeutic potential of COX2 inhibitors for enhancing recovery following periods of disuse. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Bourrant et al. (2026) studied this question.