• Media type: E-Article
  • Title: Aging, cellular senescence and disease: the influence of diet and exercise (880.7)
  • Contributor: White, Thomas; Evans, Glenda; Verzosa, Grace; Pirtskhalava, Tamara; Tchkonia, Tamara; Miller, Jordan; Kirkland, James; LeBrasseur, Nathan
  • Published: Wiley, 2014
  • Published in: The FASEB Journal
  • Extent:
  • Language: English
  • DOI: 10.1096/fasebj.28.1_supplement.880.7
  • ISSN: 0892-6638; 1530-6860
  • Keywords: Genetics ; Molecular Biology ; Biochemistry ; Biotechnology
  • Abstract: <jats:p>Nutrient excess and physical inactivity are primary drivers of numerous age‐related chronic diseases. A growing body of evidence has implicated cellular senescence, a process in which cells lose the ability to divide and concurrently damage neighboring cells by the factors they secrete, as an underlying mechanism of aging and its associated conditions. However, the impact of lifestyle choices on the age‐associated accumulation of senescent cells remains poorly understood. Thus, we examined the effects of a fast food diet (FFD) and a voluntary exercise intervention on multiple parameters of healthspan and cellular senescence using a transgenic mouse model that expresses green fluorescent protein (GFP) in p16<jats:sup>Ink4a</jats:sup>‐positive senescent cells. As expected, 12‐month old male mice that had received the FFD diet for 5 months demonstrated significantly greater gains in body weight and fat mass compared to mice fed a standard chow diet. Moreover, mice fed the FFD exhibited hyperinsulinemia, impaired glucose tolerance, reduced exercise capacity, and diastolic dysfunction. Impressively, providing an exercise wheel (26.9 ± 6.9 km/wk) in parallel with the FFD nullified the deleterious effects of the FFD on body weight and composition, whole‐body metabolism, physical performance and cardiac function. Strikingly, our data further suggest that exercise markedly lowers the number of cells in visceral fat depots that express GFP and stain positively for senescent‐associated β‐galactosidase; markers of senescence, that are highly abundant in sedentary mice fed the FFD. Correspondingly, FFD‐induced expression of senescence‐associated inflammatory factors was also diminished by the exercise intervention. Collectively, our data suggest that lifestyle choices may affect the abundance of senescence cells with advancing age, and exercise may partly mediate its salutary effects on multiple organ systems by preventing their accumulation and/or mediating their removal.</jats:p>
  • Description: <jats:p>Nutrient excess and physical inactivity are primary drivers of numerous age‐related chronic diseases. A growing body of evidence has implicated cellular senescence, a process in which cells lose the ability to divide and concurrently damage neighboring cells by the factors they secrete, as an underlying mechanism of aging and its associated conditions. However, the impact of lifestyle choices on the age‐associated accumulation of senescent cells remains poorly understood. Thus, we examined the effects of a fast food diet (FFD) and a voluntary exercise intervention on multiple parameters of healthspan and cellular senescence using a transgenic mouse model that expresses green fluorescent protein (GFP) in p16<jats:sup>Ink4a</jats:sup>‐positive senescent cells. As expected, 12‐month old male mice that had received the FFD diet for 5 months demonstrated significantly greater gains in body weight and fat mass compared to mice fed a standard chow diet. Moreover, mice fed the FFD exhibited hyperinsulinemia, impaired glucose tolerance, reduced exercise capacity, and diastolic dysfunction. Impressively, providing an exercise wheel (26.9 ± 6.9 km/wk) in parallel with the FFD nullified the deleterious effects of the FFD on body weight and composition, whole‐body metabolism, physical performance and cardiac function. Strikingly, our data further suggest that exercise markedly lowers the number of cells in visceral fat depots that express GFP and stain positively for senescent‐associated β‐galactosidase; markers of senescence, that are highly abundant in sedentary mice fed the FFD. Correspondingly, FFD‐induced expression of senescence‐associated inflammatory factors was also diminished by the exercise intervention. Collectively, our data suggest that lifestyle choices may affect the abundance of senescence cells with advancing age, and exercise may partly mediate its salutary effects on multiple organ systems by preventing their accumulation and/or mediating their removal.</jats:p>
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