Summary The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteinsin concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.

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.

SUMMARY Caloric restriction (CR) mitigates many detrimental effects of aging and prolongs lifespan. CR has been suggested to increase mitochondrial biogenesis, thereby attenuating age-related declines in mitochondrial function; a concept that is challenged by recent studies. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial oxidative capacity and efficiency, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis, which is further supported by lower mitochondrial protein synthesis with CR. We find that CR decreases oxidant emission, increases antioxidant scavenging, and minimizes oxidative damage to DNA and protein. These results demonstrate that CR preserves mitochondrial function by protecting the integrity and function of existing cellular components rather than by increasing mitochondrial biogenesis.

Influence of fish oil on skeletal muscle mitochondrial energetics and lipid metabolites during high-fat diet.

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The decline in human muscle mass and strength (sarcopenia) is a hallmark of the aging process. A growing body of research in the areas of bioenergetics and protein turnover has placed the mitochondria at the center of this process. It is now clear that unless an active life style is rigorously followed, skeletal muscle mitochondrial decline occurs as humans’ age. Increasing research on mitochondrial biology has elucidated the regulatory pathways involved in mitochondrial biogenesis, many of which are potential therapeutic targets, and highlight the beneficial effects of vigorous physical activity on skeletal muscle health for an aging population.

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Two experimental, P3-based analog control question tests were run. In both, guilty subjects were presented with a set of seven phrases describing antisocial acts of which they were innocent, plus one phrase describing a guilty act (the analog relevant question), and one act to which a "yes" response (yes-target stimulus) was required to assure attention. Innocent subjects (run only in Experiment 1) saw all innocent acts plus the yes-target act. Thus nine acts were seen by guilty and innocent subjects. In both experiments, all subjects had to selectively review their guilty acts privately. Also in both experiments, all subjects were especially questioned about four acts of which guilty subjects were known to be innocent of all but one, and of which innocent subjects were known to be innocent of all. (These falsely accused acts were regarded as control question analogs.) In Experiment 1, the private review and rehearsal took place on the same day as the main test. In Experiment 2, one subgroup (delay-only) of guilty subjects was run as in Experiment 1, except that the private review-rehearsal was separated from the main run by 7-14 days. Another subgroup (delay-rehearsal) of guilty subjects was run just as was the subgroup delay-only, except that the delay-rehearsal subgroup additionally received a non-selective additional interrogation/rehearsal on the delayed main run day. Parietally maximal P3 responses were obtained to yes-target items in all groups. In Experiment 1, only in the guilty group was the relevant-minus-control P3 amplitude difference significant. In Experiment 2, the difference was significant only in the delay-rehearsal subgroup. A four-step algorithm (involving relevant-control amplitude differences and relevant target vs. control-target cross-correlations) was used to assess effects within individuals. In Experiment 1, 12 of 13 guilty subjects and 13 of 15 innocent subjects were correctly diagnosed. In Experiment 2, 3 of 8 delay-only subjects and 7 of 8 delay-rehearsal subjects were correctly diagnosed. In Experiment 2, the relevant-minus-control group P3 amplitude difference was significant in the delay-rehearsal but not in the delay-only subgroup. The results suggest that temporally proximal, non-selective rehearsal procedures are sufficient to activate personal knowledge of a salient (oddball), P3-generating stimulus phrase, and that even selective rehearsal of guilty acts is not sufficient without temporal proximity.