scholarly journals In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use

2016 ◽  
Vol 121 (4) ◽  
pp. 996-1003 ◽  
Author(s):  
Jane A. Kent ◽  
Liam F. Fitzgerald

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo. These changes include both the maximal capacity for oxidative production of energy (ATP), as well as the relative use of mitochondrial ATP production for powering muscular activity. It has been known for nearly 50 yr that muscle mitochondrial content is highly plastic; exercise training can induce an ∼2-fold increase in mitochondrial content, while disuse has the opposite effect. Here, we suggest that a portion of the age-related changes in mitochondrial function that have been reported are likely the result of behavioral effects, as physical activity influences have not always been accounted for. Further, there is emerging evidence that various muscles may be affected differently by age-related changes in physical activity and movement patterns. In this review, we will focus on age-related changes in oxidative capacity and flux measured in vivo in human skeletal muscle.

2008 ◽  
Vol 40 (Supplement) ◽  
pp. S243
Author(s):  
Pedro A. Figueiredo ◽  
Rita M. Ferreira ◽  
Maria P. Mota ◽  
Hans J. Appell ◽  
José A. Duarte

2012 ◽  
Vol 37 (1) ◽  
pp. 88-99 ◽  
Author(s):  
Ryan G. Larsen ◽  
Damien M. Callahan ◽  
Stephen A. Foulis ◽  
Jane A. Kent-Braun

There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21–35 years) and older (8 OW, 8 OM; 65–80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, kPCr, of postcontraction phosphocreatine recovery, obtained by31P magnetic resonance spectroscopy following maximal isometric contractions. While kPCrwas higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower kPCrin VL (23%; p = 0.04). In OIW compared with OW, kPCrwas lower in VL (∼45%; p = 0.01), but not different in TA. In contrast, OAM had higher kPCrthan OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with kPCrin VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes.


1991 ◽  
Vol 276 (2) ◽  
pp. 307-313 ◽  
Author(s):  
P K Mays ◽  
R J McAnulty ◽  
J S Campa ◽  
G J Laurent

During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded.


2001 ◽  
Vol 280 (3) ◽  
pp. E413-E419 ◽  
Author(s):  
Rocco Barazzoni ◽  
K. Sreekumaran Nair

Uncoupling protein (UCP)-2 and -3 mediate mitochondrial (mt) proton leak in vitro and are potential regulators of energy expenditure and ATP production. Aging is associated with alteration of tissue functions, suggesting impaired mtATP production. To determine whether age-related changes in UCP expression occur, we measured the transcript levels of UCP-2 and -3 in skeletal muscle, liver, and heart in 6- and 27-mo-old rats. UCP-2 transcripts were higher in old animals in the white (+100%) and red (+70%, both P < 0.04) gastrocnemius muscle and in the liver (+300%, P < 0.03), whereas they were comparable in the heart in both age groups. UCP-2 transcript levels correlated positively with mitochondrial-encoded cytochrome c oxidase transcripts normalized for mtDNA ( P < 0.01) and negatively with mtDNA copy number ( P < 0.001). UCP-3 transcripts were lower in the less oxidative white (−50%, P < 0.04) and unchanged in the more oxidative red (−15%, P = 0.41) gastrocnemius muscle in old animals. Similar changes at protein level were confirmed by UCP-2 protein in aging liver (+300%, P < 0.01) and UCP-2 (+85%, P < 0.05) and UCP-3 (−30%, P = 0.4) protein in aging mixed gastrocnemius muscle. Aging is thus associated with tissue-specific changes of UCP-2 and -3 gene expression. Increased UCP-2 expression may limit ATP production and is related to mitochondrial gene expression in aging muscles and liver. Different age-related changes may reflect differential regulation of UCP-2 and -3 in skeletal muscle. The current data suggest a potential role of uncoupling proteins to alter energy production in aging tissues.


2007 ◽  
Vol 39 (Supplement) ◽  
pp. S407-S408
Author(s):  
Pedro A. Figueiredo ◽  
Rita M. Ferreira ◽  
Maria P. Mota ◽  
Hans J. Appell ◽  
José A. Duarte

1997 ◽  
Vol 83 (3) ◽  
pp. 867-874 ◽  
Author(s):  
T. W. Ryschon ◽  
M. D. Fowler ◽  
R. E. Wysong ◽  
A.-R. Anthony ◽  
R. S. Balaban

Ryschon, T. W., Fowler, R. E. Wysong, A.-R. Anthony, and R. S. Balaban. Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action. J. Appl. Physiol. 83(3): 867–874, 1997.—The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 ± 1.3% in concentric and 34.7 ± 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action.


2009 ◽  
Vol 41 ◽  
pp. 131 ◽  
Author(s):  
Ryan G. Larsen ◽  
Damien M. Callahan ◽  
Stephen A. Foulis ◽  
Jane A. Kent-Braun

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