Aged cells in human skeletal muscle after resistance exercise

Abstract

It remains unclear how exercise, as an entropic event, brings benefit against human aging. Here we examined longitudinal changes of p16Ink4a+ senescent cells in skeletal muscle of young men (aged 22.5±1.7 y) before and after resistance exercise (0 h and 48 h) with multiple biopsies at two different protein availabilities: low protein (14%) and isocaloric high protein (44%) supplemented conditions. Immunohistochemistry analysis of muscle cross-sections using p16Ink4a and CD34 antibodies confirmed that the detected senescent cells were endothelial progenitor cells. Leukocyte infiltration into skeletal muscle increased during resistance exercise. The senescent cells in muscle decreased (-48%, P < 0.01) after exercise for 48 h. Low protein supplementation resulted in greater infiltrations of both CD68+ phagocytic macrophage and leukocyte, further decreased p16Ink4a+ senescent cells (-73%, P < 0.001), and delayed increases in regenerative CD163+ macrophage in skeletal muscle, compared with high protein supplemented condition. Significant gain in muscle mass after 12 weeks of training occurred only under high protein supplemented condition. Conclusion: Rapid senescent cell clearance of human skeletal muscle during resistance exercise seems to associate with enhanced in situ phagocytosis. High protein availability accelerates resolution of muscle inflammation and promotes muscle increment after training.

In vivo analysis of γH2AX+ cells in skeletal muscle from aged and obese humans

“…Although many p16 antibodies used in previous studies of senescence are no longer available, 5,6,35 we utilized three different commercially available p16 antibodies. One, used by various labs for immunohistochemical analysis of p16, 36‐39 labeled > 60% of all nuclei in both young and old muscle (Figure S1), in spite of the fact that p16 mRNA expression is low in muscle, as is p21 mRNA (CT values 35‐36; data not shown). Consistent with mRNA results, two of the antibodies detected no p16 + cells in human skeletal muscle, regardless of age (data not shown).…”

Exercise Against Aging: Darwinian Natural Selection Among Fit and Unfit Cells Inside Human Body

“…Despite the evolvement as a highly specialized multicellular system by populating cells can increase fitness of the human body, persistent growth together with senescent cell The illustration is reproduced according to Yang et al [6] accumulation can be the fundamental cause of aging and eventual death. Exercise accelerates death of unfit senescent cells in the human body and slows down weight gain during early stage of a multicellular life.…”

“…The protein p16 INK4a is a widely used senescence marker for replicable cells, which increases as tissue ages [14]. We recently reported decreased senescent cells in capillaries of human skeletal muscle immediately after and 48 h after resistance exercise [6] (Fig. 3), suggesting death of senescent cells in tissue after exercise ( Fig.…”

“…In humans, the steepest decline in physical activity occurs during the ages of 13-18 years when body size increases rapidly [5]. Senescent cells in capillaries of human skeletal muscle can be detected by the age 20-25 years [6] (Fig. 3a).…”

“…With the same amount of protein, delayed supplementation following exercise significantly weakens muscle hypertrophy in men [20,21], suggesting a far-reaching influence of protein supplemental timing around exercise challenge on long-term muscle remodeling. We have previously shown a faster resolution of muscle inflammation occurs when higher whey protein was supplemented in a carbohydrate diet immediately after resistance exercise [6]. It is generally known that cells in human body undergoes dynamical turnover [8], the current understanding on how senescent cells are recognized and cleared in human tissues is limited by a small amount of in vivo data.…”