Life-long spontaneous exercise does not prolong lifespan but improves health span in mice

Abstract

BackgroundLife expectancy at birth in the first world has increased from 35 years at the beginning of the 20th century to more than 80 years now. The increase in life expectancy has resulted in an increase in age-related diseases and larger numbers of frail and dependent people. The aim of our study was to determine whether life-long spontaneous aerobic exercise affects lifespan and healthspan in mice.ResultsMale C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (n = 72) or spontaneous wheel-runners (n = 72). We evaluated longevity and several health parameters including grip strength, motor coordination, exercise capacity (VO2max) and skeletal muscle mitochondrial biogenesis. We also measured the cortical levels of the brain-derived neurotrophic factor (BDNF), a neurotrophin associated with brain plasticity. In addition, we measured systemic oxidative stress (malondialdehyde and protein carbonyl plasma levels) and the expression and activity of two genes involved in antioxidant defense in the liver (that is, glutathione peroxidase (GPx) and manganese superoxide dismutase (Mn-SOD)). Genes that encode antioxidant enzymes are considered longevity genes because their over-expression may modulate lifespan. Aging was associated with an increase in oxidative stress biomarkers and in the activity of the antioxidant enzymes, GPx and Mn-SOD, in the liver in mice. Life-long spontaneous exercise did not prolong longevity but prevented several signs of frailty (that is, decrease in strength, endurance and motor coordination). This improvement was accompanied by a significant increase in the mitochondrial biogenesis in skeletal muscle and in the cortical BDNF levels.ConclusionLife-long spontaneous exercise does not prolong lifespan but improves healthspan in mice. Exercise is an intervention that delays age-associated frailty, enhances function and can be translated into the clinic.

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…However, the antioxidant diet had no effect on longevity of the runners, stating that the caloric deficit induced by exercise in male rats does not have a life-extending effect that is countered by oxidative tissue damage (Holloszy 1998). In mice, life-long spontaneous exercise was found not to prolong lifespan but to improve health span (Garcia-Valles et al 2013). In this study voluntary running did prevented several aging-related signs of frailty (such as decreases in strength, endurance and motor coordination), which was accompanied by a significant increase in mitochondrial biogenesis in skeletal muscle.…”

The Neuromuscular Junction: Aging at the Crossroad between Nerves and Muscle

“…Interestingly, the decline in muscle PGC-1α levels with aging is attenuated by caloric restriction (CR) and exercise (Derbre et al, 2012; Garcia-Valles et al, 2013). …”

Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

“…It should be noted that although most studies indicate that antioxidants protect against oxidative stress and thus extend lifespan (Anisimov et al ., 2011; Niu et al ., 2013) and lead to enhanced exercise capacity (Ji et al ., 1998), recently some reports indicated that antioxidants have no beneficial effects on exercise or are even harmful in high concentrations (Selman et al ., 2013). In addition, although a number of studies have reported that exercise leads to increased longevity (Holloszy, 1998; Navarro et al ., 2004; Barnes, 2015), one study in mice is not in agreement (Garcia‐Valles et al ., 2013). However, the overwhelming preponderance of data in patients support the concept that exercise improves not only healthy lifespan, but also longevity, as it clearly is protective against cardiovascular disease, diabetes, and obesity, all of which are known to reduce lifespan.…”