Antiaging, longevity and calorie restriction.
ABSTRACT The role of calorie restriction in humans is controversial. Recently, new data in monkeys and humans have provided new insights into the potential role of calorie restriction in longevity.
A study in rhesus monkeys showed a reduction in aging-associated mortality. A number of controlled studies have suggested a variety of beneficial effects during studies of 6-12 months in humans. Major negative effects in humans were loss of muscle mass, muscle strength and loss of bone.
Dietary restriction in rodents has not been shown to be effective when started in older rodents. Weight loss in humans over 60 years of age is associated with increased mortality, hip fracture and increased institutionalization. Calorie restriction in older persons should be considered experimental and potentially dangerous. Exercise at present appears to be a preferable treatment for older persons.
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ABSTRACT: We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle-aged male Sprague Dawley rats (16-17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage-matched without running wheel access (RW-). The 9 RW+ rats averaged 83 m/day (range: 8-163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross-sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B-II/-I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low-volume voluntary running wheel activity is associated with decreases in many long-chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW- rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle-age promote extensive metabolic remodeling of skeletal muscle. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.02/2015; 3(2). DOI:10.14814/phy2.12319
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ABSTRACT: Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass. Participants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance. Twelve months of PRT tended to reduce CRP compared to sham exercise (β = -0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively). We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations.Journal of Cachexia, Sarcopenia and Muscle 02/2014; 5(2):111-120. DOI:10.1007/s13539-014-0134-1 · 7.41 Impact Factor
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ABSTRACT: Objective To assess the long-term effects of an intensive lifestyle intervention on physical function using a randomized post-test design in the Look AHEAD trial.Methods Overweight and obese (BMI ≥ 25 kg m−2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes (n = 964) at four clinics in Look AHEAD, a trial evaluating an intensive lifestyle intervention (ILI) designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including an expanded short physical performance battery (SPPBexp), 20-m and 400-m walk, and grip and knee extensor strength 8 years post-randomization, during the trial's weight maintenance phase.ResultsEight years post-randomization, individuals randomized to ILI had better SPPBexp scores [adjusted mean (SE) difference: 0.055 (0.022), P = 0.01] and faster 20-m and 400-m walk speeds [0.032 (0.012) m s−1, P = 0.01, and 0.025 (0.011) m s−1, P = 0.02, respectively] compared to those randomized to DSE. Achieved weight loss greatly attenuated the group differences in physical function, and the intervention effect was no longer significant.Conclusions An intensive lifestyle intervention has long-term benefits for mobility function in overweight and obese middle-aged and older individuals with type 2 diabetes.Obesity 01/2015; 23(1). DOI:10.1002/oby.20944 · 4.39 Impact Factor