Effects of aging and lifelong aerobic exercise on expression of innate immune components in human skeletal muscle.

The purpose of this investigation was to evaluate the effects of aging and lifelong exercise on skeletal muscle components of the innate immune system. Additionally, the effects of an acute resistance exercise (RE) challenge were explored. Three groups of men were studied: young exercisers (YE: n = 10, 25 ± 1 yr; V̇o2max: 53 ± 3 mL/kg/min; quadriceps size: 78 ± 3 cm2), lifelong aerobic exercisers with a 53 ± 1 yr training history (LLE; n = 21, 74 ± 1 yr; V̇o2max: 34 ± 1 mL/kg/min; quadriceps size: 67 ± 2 cm2), and old healthy nonexercisers (OH: n = 10, 75 ± 1 yr; V̇o2max: 22 ± 1 mL/kg/min, quadriceps size: 56 ± 3 cm2). Vastus lateralis muscle biopsies were obtained in the basal state and 4 h after RE (3 × 10 reps, 70% of 1 repetition maximum) to assess Toll-like receptors (TLR)1-10, TLR adaptors (Myd88 and TRIF), and NF-κB pathway components (IκΒα and IKKβ) mRNA expression. Basal TLR3, TLR6, and TLR7 tended to be higher (P ≤ 0.10) with aging (LLE and OH combined). In general, RE increased expression of TLR1 and TLR8 (P ≤ 0.10) and TLR3 and TLR4 (P < 0.05), although TLR3 did not respond in OH. Both TLR adaptors also responded to the exercise bout; these were primarily (Myd88, main effect P ≤ 0.10) or exclusively (TRIF, P < 0.05) driven by the OH group. In summary, aging appears to increase basal expression of some innate immune components in human skeletal muscle, and lifelong aerobic exercise does not affect this age-related increase. An exercise challenge stimulates the expression of several TLRs, while the TLR adaptor response appears to be dysregulated with aging and maintained with lifelong exercise. Partially preserved muscle mass, coupled with a notable immunity profile, suggests lifelong exercisers are likely better prepared for a stress that challenges the immune system.NEW & NOTEWORTHY Findings from this investigation provide novel insight into the effect of aging and lifelong aerobic exercise on structural components of the innate immune system in skeletal muscle of humans. Data presented here suggest aging increases basal expression of select Toll-like receptors (TLRs), and lifelong exercise does not impact this age-related increase. Additionally, acute exercise stimulates gene expression of several TLRs, while the adaptor response is likely dysregulated with aging and maintained with lifelong exercise.