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Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults.

Safdar A, Hamadeh MJ, Kaczor JJ, Raha S, Debeer J, Tarnopolsky MA - PLoS ONE (2010)

Bottom Line: What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports.Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity.We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

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Related in: MedlinePlus

Mitochondrial Mn-SOD activity is reduced in frail old.(A) Mn-SOD protein content and (B) total- and Mn- SOD activity (U.mg of protein−1) in the vastus lateralis of young, AO, and SO subjects (N = 10/group; ♀  =  ♂). Asterisk denotes significant changes vs. young, and dagger denotes significant changes vs. AO (P≤0.05).
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pone-0010778-g003: Mitochondrial Mn-SOD activity is reduced in frail old.(A) Mn-SOD protein content and (B) total- and Mn- SOD activity (U.mg of protein−1) in the vastus lateralis of young, AO, and SO subjects (N = 10/group; ♀  =  ♂). Asterisk denotes significant changes vs. young, and dagger denotes significant changes vs. AO (P≤0.05).

Mentions: During the aging process, the rate of superoxide radical (O-.2) generation increases [49]. Both cytosolic and mitochondrial superoxide dismutases function as a first line of defence against oxidative stress-mediated by O-.2 [50]. The protein content of mitochondrial Mn-SOD was significantly lower in the SO group relative to both the young and AO groups (85% and 69%, respectively; P<0.001) (Figure 3A). The total-SOD and Mn-SOD activity were significantly lower in the SO group compared with the young (14% and 26%, respectively; P<0.03) and AO (24% and 32%, respectively; P<0.03) groups (Figure 3B). Surprisingly, no significant differences in both the total-SOD and Mn-SOD activity were detected between the AO and young groups (Figure 3B); even though the AO group has 55% lower Mn-SOD protein content when compared to the young (P<0.001) (Figure 3A). There was no difference in cytosolic Cu/Zn-SOD protein content and enzyme activity between the three groups (data not shown). Since aging in skeletal muscle is widely related to increases in O-.2 production via mitochondrial ETC, we suggest that physical activity maintains mitochondrial Mn-SOD activity in AO individuals at levels observed in much younger individuals despite significant reductions in the Mn-SOD protein content.


Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults.

Safdar A, Hamadeh MJ, Kaczor JJ, Raha S, Debeer J, Tarnopolsky MA - PLoS ONE (2010)

Mitochondrial Mn-SOD activity is reduced in frail old.(A) Mn-SOD protein content and (B) total- and Mn- SOD activity (U.mg of protein−1) in the vastus lateralis of young, AO, and SO subjects (N = 10/group; ♀  =  ♂). Asterisk denotes significant changes vs. young, and dagger denotes significant changes vs. AO (P≤0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875392&req=5

pone-0010778-g003: Mitochondrial Mn-SOD activity is reduced in frail old.(A) Mn-SOD protein content and (B) total- and Mn- SOD activity (U.mg of protein−1) in the vastus lateralis of young, AO, and SO subjects (N = 10/group; ♀  =  ♂). Asterisk denotes significant changes vs. young, and dagger denotes significant changes vs. AO (P≤0.05).
Mentions: During the aging process, the rate of superoxide radical (O-.2) generation increases [49]. Both cytosolic and mitochondrial superoxide dismutases function as a first line of defence against oxidative stress-mediated by O-.2 [50]. The protein content of mitochondrial Mn-SOD was significantly lower in the SO group relative to both the young and AO groups (85% and 69%, respectively; P<0.001) (Figure 3A). The total-SOD and Mn-SOD activity were significantly lower in the SO group compared with the young (14% and 26%, respectively; P<0.03) and AO (24% and 32%, respectively; P<0.03) groups (Figure 3B). Surprisingly, no significant differences in both the total-SOD and Mn-SOD activity were detected between the AO and young groups (Figure 3B); even though the AO group has 55% lower Mn-SOD protein content when compared to the young (P<0.001) (Figure 3A). There was no difference in cytosolic Cu/Zn-SOD protein content and enzyme activity between the three groups (data not shown). Since aging in skeletal muscle is widely related to increases in O-.2 production via mitochondrial ETC, we suggest that physical activity maintains mitochondrial Mn-SOD activity in AO individuals at levels observed in much younger individuals despite significant reductions in the Mn-SOD protein content.

Bottom Line: What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports.Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity.We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

Show MeSH
Related in: MedlinePlus