Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults

Abstract

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.

Fig. 1. Expression of senescence-associated genes in the colon mucosa of master athletes and sedentary controls.

RNA was extracted from the sigmoid portion of the colon of human volunteers. The groups were: EX, exercised volunteers of average age 57 ± 10 years; age-matched sedentary controls (SED); young, volunteers of average age 24.3 ± 2 years. mRNA encoding p16 (A), p21 (B), IL6 (C), IL8 (D), and MMP3 (E) were quantified by qRT-PCR. mRNA encoding tubulin was used as internal control (N = 5–11 with each sample indicated by an individual dot). Panel F shows the relationship between p16 mRNA levels and the triglycerides to HDL ratio. All values are represented together with means and SEM. One-way Anova, *p < 0.05.