Effect of exercise and calorie restriction on biomarkers of aging in mice

Abstract

Unlike calorie restriction, exercise fails to extend maximum life span, but the mechanisms that explain this disparate effect are unknown. We used a 24-wk protocol of treadmill running, weight matching, and pair feeding to compare the effects of exercise and calorie restriction on biomarkers related to aging. This study consisted of young controls, an ad libitum-fed sedentary group, two groups that were weight matched by exercise or 9% calorie restriction, and two groups that were weight matched by 9% calorie restriction ϩ exercise or 18% calorie restriction. After 24 wk, ad libitum-fed sedentary mice were the heaviest and fattest. When weight-matched groups were compared, mice that exercised were leaner than calorie-restricted mice. Ad libitum-fed exercise mice tended to have lower serum IGF-1 than fully-fed controls, but no difference in fasting insulin. Mice that underwent 9% calorie restriction or 9% calorie restriction ϩ exercise, had lower insulin levels; the lowest concentrations of serum insulin and IGF-1 were observed in 18% calorie-restricted mice. Exercise resulted in elevated levels of tissue heat shock proteins, but did not accelerate the accumulation of oxidative damage. Thus, failure of exercise to slow aging in previous studies is not likely the result of increased accrual of oxidative damage and may instead be due to an inability to fully mimic the hormonal and/or metabolic response to calorie restriction. energetics; obesity; energy balance CALORIE RESTRICTION provides a powerful and widely applicable intervention for attenuating many age-related diseases and extending maximal life span (41). Despite its well-documented benefits, limiting calorie intake (Ͼ30%) alone may not provide a practical long-term solution for maximizing human health and longevity. Instead, an alternative approach to energy deprivation could be to increase activity-related energy expenditure or to supplement moderate calorie restriction with exercise.Several studies have reported that increased physical activity can improve mean life span presumably by reducing mortality risk from many age-related diseases, including cardiovascular disease, stroke, type 2 diabetes, and certain cancers (9,17,21,(27)(28)(29). In contrast, exercise and longevity studies in rodents (17, 21) and humans (32) have failed to document an exercise effect on maximum life span. For example, it was found in rats that exercise improved survival (mean life span) compared with sedentary ad libitum-fed controls, but did not result in life span extension (17)(18)(19)21). Furthermore, when exercising rats were matched for body weight with food-restricted pairedweight sedentary rats, only the food-restricted rats had an increase in maximum life span (21).Although the evidence clearly shows a greater benefit from calorie restriction compared with exercise on longevity, there remains a significant gap in the literature explaining this disparate effect. The effects of calorie restriction (40) and exercise (6) on age-related diseases and markers of aging have be...

Central insulin‐like growth factor‐1 ( IGF ‐1) restores whole‐body insulin action in a model of age‐related insulin resistance and IGF ‐1 decline

“…Body weight was determined on a digital scale, and body composition was assessed by quantitative magnetic resonance for the determination of fat and lean mass in young and old animals ( n  = 8 per group) similar to the method previously described (Echo Medical Systems, Houston, TX, USA) (Huffman et al ., 2008, 2013). Energy expenditure and substrate utilization were determined by indirect calorimetry as described (Huffman et al ., 2007), based on O 2 consumption and CO 2 production, using a Rat Oxymax System (Columbus Instruments, Columbus, OH, USA).…”

“…Total MBH protein was extracted with a modified RIPA buffer, and protein content was determined using the BCA protein assay (Sigma, St. Louis, MO, USA) with BSA as a standard. Western blotting was performed similarly as described (Huffman et al ., 2008; Muzumdar et al ., 2010). In brief, 20 μg of total protein was loaded onto 4–15% Bis–Tris stain‐free gels and electrophoresed at 120 V constant for 90 min ( n  = 12 per group).…”

Age-Accelerated Atherosclerosis Correlates With Failure to Upregulate Antioxidant Genes

“…[7][8][9][10] Caloric restriction attenuates the increases in inflammation, oxidative stress, and endothelial dysfunction that accompany aging and has been shown to extend median lifespan in several animal models. [11][12][13][14][15] Conversely, caloric excess leading to obesity worsens these factors and promotes insulin resistance, metabolic syndrome, and diabetes, all of which are frequently associated with aging and are known contributors to accelerated atherosclerosis. 16 -18 We, therefore, examined the effect of age on atherosclerosis and insulin resistance in lipoprotein receptor knockout (LDLR Ϫ/Ϫ ) mice fed a high fat diet (HFD) to elucidate mechanisms by which aging promotes vascular injury.…”

Aging and longevity science: where are we in 2015?

“…(Holloszy 1997;Holloszy 212 1998) Compared to a weight-matched sedentary CR mouse, the physically active mouse was significantly 213 leaner; however, the elongation in lifespan was still observed in the CR mouse. (Huffman et al 2008) The 214 explanations behind these findings are debated. One age-modifying aspect of physical activity is muscular 215 function.…”