We sought to determine whether lipolysis, fatty acid (FA) mobilization, and plasma FA oxidation would remain elevated for hours following isoenergetic exercise bouts of different intensities. Ten men and eight women received a primed-continuous infusion of [1,1,2,3,3-2 H 5 ]glycerol and continuous infusion of [1-13 C]palmitate to measure glycerol and plasma FA kinetics. On Day 1 (D1), participants were studied under one of three different conditions, assigned in random order: (1) before, during and 3 h after 90 min of exercise at 45%V O 2 peak (E45), (2) before, during and 3 h after 60 min of exercise at 65%V O 2 peak (E65), and (3) in a time-matched sedentary control trial (C). For each condition, participants were studied by indirect calorimetry the following morning as well (D2). Rate of appearance (Ra) of glycerol (Ra GL ) increased above C during exercise in men and women (P < 0.05), was higher in E45 than E65 in men (P < 0.05), and was not different between exercise intensities in women. During 3 h of postexercise recovery, Ra GL remained significantly elevated in men (P < 0.05), but not women. FA Ra (Ra FA ) increased during exercise in men and women and was higher in E45 than E65 (P < 0.05), and remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05), but with a greater relative increase in men than women (P < 0.05). Plasma FA oxidation (Rox) increased during exercise with no difference between intensities, and it remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05). Total lipid oxidation (Lox) was elevated in both sexes (P < 0.05), but more in men during 3 h of postexercise recovery on D1 (P < 0.05) and remained elevated on D2 in men (P < 0.05), but not in women. There were no differences between E45 and E65 for postexercise energy substrate turnover or oxidation in men and women as energy expenditure of exercise (EEE) was matched between bouts. We conclude that the impact of exercise upon lipid metabolism persists into recovery, but that women depend more on lipid during exercise whereas, during recovery, lipid metabolism is accentuated to a greater extent in men.

Collectively, these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured. In conclusion, CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age.

We investigated age and sex effects and determined whether androgen replacement in elderly individuals (> or = 60 yr) could augment protein synthesis. Thirty young men and 32 young women (18-31 yr) were studied once, whereas 87 elderly men were studied before and after 1 yr of treatment with 5 mg/day testosterone (T), 75 mg/day dehydroepiandrosterone (DHEA), or placebo (P); and 57 elderly women were studied before and after 1 yr of treatment with 50 mg/day DHEA or P. [(15)N]Phenylalanine and [(2)H(4)]tyrosine tracers were infused, with measurements in plasma and vastus lateralis muscle. Whole-body protein synthesis per fat-free mass and muscle protein fractional synthesis rate (FSR) were lower in elderly than in young individuals (P<0.001), not significantly affected by hormone treatments, and higher in women than in men (P<0.0001), with no sex x age interaction. In regression analyses, peak O2 consumption (VO2peak), resting energy expenditure (REE), and sex were independently associated with muscle FSR, as were VO2peak, REE, and interactions of sex with insulin-like growth factor-II and insulin for whole-body protein synthesis. Women maintain higher protein synthesis than men across the lifespan as rates decline in both sexes, and neither full replacement of DHEA (in elderly men and women) nor partial replacement of bioavailable T (in elderly men) is able to amend the age-related declines.

Acute aerobic exercise increases reactive oxygen species and could potentially damage proteins, but exercise training (ET) enhances mitochondrial respiration irrespective of age. Here, we report a differential impact of ET on protein quality in young and older participants. Using mass spectrometry we measured oxidative damage to skeletal muscle proteins before and after 8 weeks of ET and find that young but not older participants reduced oxidative damage to both total skeletal muscle and mitochondrial proteins. Young participants showed higher total and mitochondrial derived semitryptic peptides and 26S proteasome activity indicating increased protein degradation. ET however, increased the activity of the endogenous antioxidants in older participants. ET also increased skeletal muscle content of the mitochondrial deacetylase SIRT3 in both groups. A reduction in the acetylation of isocitrate dehydrogenase 2 was observed following ET that may counteract the effect of acute oxidative stress. In conclusion aging is associated with an inability to improve skeletal muscle and mitochondrial protein quality in response to ET by increasing degradation of damaged proteins. ET does however increase muscle and mitochondrial antioxidant capacity in older individuals, which provides increased buffering from the acute oxidative effects of exercise.

Diet-induced insulin resistance (IR) adversely affects human health and life span. We show that muscle-specific overexpression of human mitochondrial transcription factor A (TFAM) attenuates high-fat diet (HFD)–induced fat gain and IR in mice in conjunction with increased energy expenditure and reduced oxidative stress. These TFAM effects on muscle are shown to be exerted by molecular changes that are beyond its direct effect on mitochondrial DNA replication and transcription. TFAM augmented the muscle tricarboxylic acid cycle and citrate synthase facilitating energy expenditure. TFAM enhanced muscle glucose uptake despite increased fatty acid (FA) oxidation in concert with higher β-oxidation capacity to reduce the accumulation of IR-related carnitines and ceramides. TFAM also increased pAMPK expression, explaining enhanced PGC1α and PPARβ, and reversing HFD-induced GLUT4 and pAKT reductions. TFAM-induced mild uncoupling is shown to protect mitochondrial membrane potential against FA-induced uncontrolled depolarization. These coordinated changes conferred protection to TFAM mice against HFD-induced obesity and IR while reducing oxidative stress with potential translational opportunities.