Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

Picard, Martin; Ritchie, Debbie; Thomas, Melissa M.; Wright, Kate; Hepple, Russell T.

doi:10.1111/j.1474-9726.2011.00745.x

Cited by 124 publications

(147 citation statements)

References 46 publications

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“…When complex I was bypassed to measure uncoupled complex II, there was also a decrease with age in SOL, and complex IV flux was not different with age in either EDL or SOL. These differences in the effect of age on mitochondrial function between fast‐ and slow‐type skeletal muscles are consistent with previous work in aging rat skeletal muscle (Picard et al ., 2011). …”

Section: Resultsmentioning

confidence: 99%

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

et al. 2015

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SummaryChanges in mitochondrial function with age vary between different muscle types, and mechanisms underlying this variation remain poorly defined. We examined whether the rate of mitochondrial protein turnover contributes to this variation. Using heavy label proteomics, we measured mitochondrial protein turnover and abundance in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) from young and aged mice. We found that mitochondrial proteins were longer lived in EDL than SOL at both ages. Proteomic analyses revealed that age‐induced changes in protein abundance differed between EDL and SOL with the largest change being increased mitochondrial respiratory protein content in EDL. To determine how altered mitochondrial proteomics affect function, we measured respiratory capacity in permeabilized SOL and EDL. The increased mitochondrial protein content in aged EDL resulted in reduced complex I respiratory efficiency in addition to increased complex I‐derived H2O2 production. In contrast, SOL maintained mitochondrial quality, but demonstrated reduced respiratory capacity with age. Thus, the decline in mitochondrial quality with age in EDL was associated with slower protein turnover throughout life that may contribute to the greater decline in mitochondrial dysfunction in this muscle. Furthermore, mitochondrial‐targeted catalase protected respiratory function with age suggesting a causal role of oxidative stress. Our data clearly indicate divergent effects of age between different skeletal muscles on mitochondrial protein homeostasis and function with the greatest differences related to complex I. These results show the importance of tissue‐specific changes in the interaction between dysregulation of respiratory protein expression, oxidative stress, and mitochondrial function with age.

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Section: Resultsmentioning

confidence: 99%

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

et al. 2015

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“…An enhanced susceptibility to mPTP opening was also found in brain (Krestinina et al., 2015; Marques‐Aleixo et al., 2012; Mather & Rottenberg, 2000) and appeared to depend on the brain area tested (Brown, Geddes, & Sullivan, 2004; LaFrance, Brustovetsky, Sherburne, Delong, & Dubinsky, 2005), in the liver (Goodell & Cortopassi, 1998; Mather & Rottenberg, 2000), and in lymphocytes (Rottenberg & Wu, 1997). More recently, Picard, Ritchie, Thomas, Wright, and Hepple (2011) described an impaired mPTP function with aging in fast muscles of the rat that was also observed in aged human muscles (Gouspillou et al., 2014), showing that this phenomenon is not restricted to animal models of aging. Sensitization of mPTP opening was also involved in the bone loss occurring in aging mice (Shum et al., 2016).…”

Section: Experimental Evidence Supporting the Involvement Of The Mptpmentioning

confidence: 94%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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“…Interestingly, one such study reported a muscledependent decrease in state III respiration with age in rats, such that muscles with a slower phenotype exhibit a reduced oxidative capacity with age and muscle with a faster phenotype demonstrate a propensity for preservation with age (Picard et al 2011a …”

Section: R a F Tmentioning

confidence: 99%

Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis

Fitzgerald

Christie

Kent

2016

Appl. Physiol. Nutr. Metab.

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https://mc06.manuscriptcentral.com/apnm-pubs Applied Physiology, Nutrition, and Metabolism D r a f t 2 ABSTRACTDespite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including: muscle group, physical activity status, and sex. Candidate papers were identified from PubMed searches (n=3,561 papers) and the reference lists of relevant papers. Standardized effects (Hedges' g) were calculated for age and each moderator using data from the 22 studies that met the inclusion criteria (n=28 effects). Effects were coded as positive when older (≥55 years) adults had higher muscle oxidative capacity than younger (20-45 years) adults. The overall effect of age on oxidative capacity was positive (g=0.171, p<0.001), indicating modestly greater oxidative capacity in old. Notably, there was significant heterogeneity in this result (Q=245.8, p<0.001; I 2 ~70-90%). Muscle group, physical activity, and sex were all significant moderators of oxidative capacity (p≤0.029). This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age. The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature, and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity.

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Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

Cited by 124 publications

References 46 publications

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

Mitochondria and aging: A role for the mitochondrial transition pore?

Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis

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