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

Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana
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引用次数: 2

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.

Abstract Image

长期高强度耐力运动训练与老年人结肠黏膜细胞衰老标志物的减少有关。
定期的耐力运动训练是维持代谢健康和预防许多与年龄相关的慢性疾病的有效干预措施。几种代谢和炎症因子参与运动训练的健康促进作用,但调节机制仍然知之甚少。细胞衰老——一种不可逆转的生长停滞状态——被认为是衰老的基本机制。随着时间的推移,衰老细胞积累并促进各种与年龄相关的病理,从神经退行性疾病到癌症。长期高强度运动训练是否会影响与年龄相关的细胞衰老的积累尚不清楚。在这里,我们发现经典衰老标志物p16和IL-6在中老年超重成年人的结肠粘膜中明显高于年轻久坐的个体,但这种上调在年龄匹配的耐力跑步者中明显减弱。有趣的是,我们观察到p16水平与甘油三酯与高密度脂蛋白比率(结肠腺瘤风险和心脏代谢功能障碍的标志)之间存在线性相关。我们的数据表明,随着年龄的增长,慢性大容量、高强度的耐力运动可以防止衰老细胞在结肠黏膜等易发癌症组织中积累。未来的研究有必要阐明其他组织是否也受到影响,以及不同形式的运动训练介导衰老预防作用的分子和细胞机制是什么。
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