Decline In Oxidative Capacity Research Articles

High Levels of Physical Activity in Later Life Are Associated With Enhanced Markers of Mitochondrial Metabolism.

The age-associated reduction in muscle mass is well characterized; however, less is known regarding the mechanisms responsible for the decline in oxidative capacity also observed with advancing age. The purpose of the current study was therefore to compare mitochondrial gene expression and protein content between young and old recreationally active, and older highly active individuals. Muscle biopsies were obtained from the vastus lateralis of young males (YG: 22 ± 3 years) and older (OG: 67 ± 2 years) males not previously engaged in formal exercise and older male master cyclists (OT: 65 ± 5 years) who had undertaken cycling exercise for 32 ± 17 years. Comparison of gene expression between YG, OG, and OT groups revealed greater expression of mitochondrial-related genes, namely, electron transport chain (ETC) complexes II, III, and IV (p < .05) in OT compared with YG and OG. Gene expression of mitofusion (MFN)-1/2, mitochondrial fusion genes, was greater in OT compared with OG (p < .05). Similarly, protein content of ETC complexes I, II, and IV was significantly greater in OT compared with both YG and OG (p < .001). Protein content of peroxisome proliferator-activated receptor gamma, coactivator 1 α (PGC-1α), was greater in OT compared with YG and OG (p < .001). Our results suggest that the aging process per se is not associated with a decline in gene expression and protein content of ETC complexes. Mitochondrial-related gene expression and protein content are substantially greater in OT, suggesting that exercise-mediated increases in mitochondrial content can be maintained into later life.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Muscle Oxidative Capacity in Older Adults.

Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). NIA IRP Clinical Research Unit, Baltimore, MD. Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr ; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. In linear regression models, higher τPCr was associated with older age (standardized β = .39; P < .001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τPCr (βage = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (βMVPA = -.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (βage = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (βMVPA = -.32; P < .001). Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695-1699, 2019.

Mitochondrial Aging and Physical Decline: Insights From Three Generations of Women.

Decline in mitochondrial DNA (mtDNA) copy number, function, and accumulation of mutations and deletions have been proposed to contribute to age-related physical decline, based on cross sectional studies in genetically unrelated individuals. There is wide variability of mtDNA and functional measurements in many population studies and therefore we assessed mitochondrial function and physical function in 18 families of grandmothers, mothers, and daughters who share the same maternally inherited mtDNA sequence. A significant age-related decline in mtDNA copy number, mitochondrial protein expression, citrate synthase activity, cytochrome c oxidase content, and VO2 peak were observed. Also, a lower abundance of SIRT3, accompanied by an increase in acetylated skeletal muscle proteins, was observed in grandmothers. Muscle tissue-based full sequencing of mtDNA showed greater than 5% change in minor allele frequency over a lifetime in two locations, position 189 and 408 in the noncoding D-loop region but no changes were noted in blood cells mtDNA. The decline in oxidative capacity and muscle function with age in three generations of women who share the same mtDNA sequence are associated with a decline in muscle mtDNA copy number and reduced protein deacetylase activity of SIRT3.

Reduced muscle oxidative capacity is independent of O2 availability in elderly people

Impaired O2 transport to skeletal muscle potentially contributes to the decline in aerobic capacity with aging. Thus, we examined whether (1) skeletal muscle oxidative capacity decreases with age and (2) O2 availability or mitochondrial capacity limits the maximal rate of mitochondrial ATP synthesis in vivo in sedentary elderly individuals. We used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine the PCr recovery kinetics in six young (26 ± 10 years) and six older (69 ± 3 years) sedentary subjects following 4 min of dynamic plantar flexion exercise under different fractions of inspired O2 (FiO2, normoxia 0.2; hyperoxia 1.0). End-exercise pH was not significantly different between old (7.04 ± 0.10) and young (7.05 ± 0.04) and was not affected by breathing hyperoxia (old 7.08 ± 0.08, P > 0.05 and young 7.05 ± 0.03). Likewise, end-exercise PCr was not significantly different between old (19 ± 4 mM) and young (24 ± 5 mM) and was not changed in hyperoxia. The PCr recovery time constant was significantly longer in the old (36 ± 9 s) compared to the young in normoxia (23 ± 8 s, P < 0.05) and was not significantly altered by breathing hyperoxia in both the old (35 ± 9 s) and young (29 ± 10 s) groups. Therefore, this study reveals that the muscle oxidative capacity of both sedentary young and old individuals is independent of O2 availability and that the decline in oxidative capacity with age is most likely due to limited mitochondrial content and/or mitochondrial dysfunction and not O2 availability.

The time course of denervation-induced changes is similar in soleus muscles of adult and old rats

Muscle denervation is accompanied by atrophy and a decline in oxidative capacity. We investigated whether the time course of adaptations following denervation of the soleus muscle differs in adult (5 months old) and older adult (25 months old) rats. We denervated the soleus muscle of the left leg, while the right leg served as an internal control. Two weeks after denervation, muscle mass was decreased both in adult and old animals to, respectively, 57% and 54% (p < 0.001) and capillary to fibre ratio (C:F) decreased to 51% and 50% (p < 0.01) of the control values. Yet, the capillary density was increased in older adult but not in adult muscles, indicating that the regression of the capillary bed during denervation lags behind the decrease in fibre size in the soleus muscle of the older rats. One week after denervation the optical density of sections stained for succinate dehydrogenase was 83% and 79% (p < 0.05) of control adult and older adult muscles, respectively, and then remained stable. This indicates that during the first week of denervation loss of oxidative capacity occurred at a relatively higher rate than that of muscle mass. No major changes occurred between 2 and 4 weeks of denervation, except for an increase in the proportion of hybrid (I/IIa) fibres in 4 week denervated muscles (adult 10% vs. 23%; old 1% vs. 13%; p < 0.05). Except for changes in capillarisation, the time course of atrophy and decrease in oxidative capacity following denervation was similar in soleus muscles from adult and old rats.

Skeletal muscle oxidative capacity in young and older women and men.

It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [n = 19; 33.8 +/- 4.8 (SD) yr] and older [n = 18; 75.5 +/- 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery, thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.