Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

Kim, Jong-Hee; Kwak, Hyo‐Bum; Leeuwenburgh, Christiaan; Lawler, John M.

doi:10.1016/j.exger.2007.12.012

Cited by 68 publications

(82 citation statements)

References 70 publications

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“…We then assessed the effects of caloric restriction and exercise on these synaptic changes. Both of these interventions attenuate age-related declines in muscle function (20)(21)(22)(23)(24), but little is known about their effects on the NMJ (25). We show here that both conditions significantly blunt age-related structural alterations in the NMJ.…”

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confidence: 58%

Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

Valdez

Tapia

Kang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

433

540

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The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre-and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.aging | neuromuscular junction | muscle | motor neuron | sarcopenia A ging is accompanied by numerous functional alterations of both the central and peripheral nervous systems (1). Until recently, it was thought that many of these age-associated changes were secondary to neuronal degeneration. Recent studies show, however, that little neuronal death occurs in most areas of the aging nervous system (2). Although many possible explanations exist (3-6), a particularly attractive hypothesis is that some agerelated alterations in mental function result from synaptic alterations. Supporting this idea, alterations in synapse number, spine densities, and synaptic plasticity have been documented in the brains of aging humans and experimental animals (1,7,8).If synaptic changes underlie age-related defects in neural function, one might look to synapses as targets for treatments that minimize the decline. Two lifestyle regimens that have been consistently demonstrated to extend lifespan and mitigate agerelated changes in neural function are caloric restriction and exercise (9). In that the cellular bases of age-related changes in mental activity are obscure, it is not surprising that the means by which exercise and caloric restriction attenuate these changes are also unknown. For both regimens, however, synaptic alterations have figured prominently among proposed mechanisms (9, 10).An obstacle to progress in this area is the complexity and diversity of synaptic neuropil in the brain, which impedes detailed analysis of aging central syna...

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confidence: 58%

Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

Valdez

Tapia

Kang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

433

540

View full text Add to dashboard Cite

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“…1. Lifelong wheel running and mild caloric restriction alleviate age-associated reduction in muscle fiber cross-sectional area (51). Plantaris muscle fiber crosssectional area in young (6 months) Fischer-344 rats fed ad libitum (YAL), old (24 months) rats fed ad libitum (OAL), old rats that underwent lifelong 8% caloric restriction (OCR), and old rats that participated in lifelong voluntary wheel running plus 8% caloric restriction (OExCR).…”

Section: Lifelong Voluntary Exercise In Ameliorating Sarcopeniamentioning

confidence: 99%

Living in a Box or Call of the Wild? Revisiting Lifetime Inactivity and Sarcopenia

Lawler

Hindle

2011

Antioxidants & Redox Signaling

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“…Such treatment (Carter et al 2007;Fontana 2009) induces both changes shared by all tissues as well as marked tissue-specific effects (Anderson and Weindruch 2010;Kim et al 2008;Opalach et al 2010;Rangaraju et al 2009;Seo et al 2006). The common changes include: (a) coordinated increase in the expression of genes involved in the mitochondrial energy metabolism; (b) improved sensitivity of insulin signaling; (c) increased levels of the circulating adipokine, adiponectin, which counteract some wellrecognized features of the aging process.…”

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confidence: 99%

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

Picca

Fracasso

Pesce

et al. 2012

AGE

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Aging markedly affects mitochondrial biogenesis and functions particularly in tissues highly dependent on the organelle's bioenergetics capability such as the brain's frontal cortex. Calorie restriction (CR) diet is, so far, the only intervention able to delay or prevent the onset of several age-related alterations in different organisms. We determined the contents of mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), and the 4.8-kb mtDNA deletion in the frontal cortex from young (6-monthold) and aged (26-month-old), ad libitum-fed (AL) and calorie-restricted (CR), rats. We found a 70 % increase in TFAM amount, a 25 % loss in mtDNA content, and a 35 % increase in the 4.8-kb deletion content in the aged AL animals with respect to the young rats. TFAM-specific binding to six mtDNA regions was analyzed by mtDNA immunoprecipitation and semiquantitative polymerase chain reaction (PCR), showing a marked age-related decrease. Quantitative realtime PCR at two subregions involved in mtDNA replication demonstrated, in aged AL rats, a remarkable decrease (60-70 %) of TFAM-bound mtDNA. The decreased TFAM binding is a novel finding that may explain the mtDNA loss in spite of the compensatory TFAM increased amount. In aged CR rats, TFAM amount increased and mtDNA content decreased with respect to young rats' values, but the extent of the changes was smaller than in aged AL rats. Attenuation of the age-related effects due to the diet in the CR animals was further evidenced by the unchanged content of the 4.8-kb deletion with respect to that of young animals and by the partial prevention of the age-related decrease in TFAM binding to mtDNA.

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Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

Cited by 68 publications

References 70 publications

Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

Living in a Box or Call of the Wild? Revisiting Lifetime Inactivity and Sarcopenia

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

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