Abstract
Background: Frailty is a clinical condition associated with loss of muscle mass and strength (sarcopenia). Mitochondria are centrally implicated in frailty and sarcopenia. Leucine (Leu) can alter mitochondrial content in myocytes, while resistance training (RT) is the strongest stimulus to counteract sarcopenia and may enhance mitochondrial biogenesis.Objective: We determined the effects of Leu supplementation and RT on mitochondrial content and function in pre/frail elderly women in a randomized double-blinded placebo-controlled study.Methods: Nineteen pre/frail elderly women (77.5 ± 1.3 y, BMI: 25.1 ± 0.9 kg/m2), based on the Frailty Phenotype, underwent 3-months of RT 3×/week with protein-optimized diet and were randomized to 7.5 g/d of Leu supplementation or placebo alanine (Ala). Pre/post-intervention mitochondrial respiration, reactive oxygen species (ROS) production, calcium retention capacity (CRC), time to permeability transition pore (mPTP) opening, mitochondrial voltage-dependent anion channel (VDAC) protein content, leg press 1-repetition maximum (1RM), and 6-min walk test (6MWT) were measured.Results: No time, supplementation, or interaction effects were observed for respiration, ROS, time to mPTP opening, and CRC. VDAC levels significantly increased in the Leu group post-intervention (p = 0.012). Both groups significantly increased leg press 1RM and 6MWT, with no effect of supplementation.Discussion: Leu supplementation with 3 months of RT increased mitochondrial content. Future studies should investigate if there is an increase in mitochondrial turnover or a shift in quality control (mitophagy) in leucine supplemented pre/frail elderly women who undergo 12 weeks of RT.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01922167.
Highlights
The World Health Organization has predicted that globally, by 2050 those over 60 years old will double from about 11 to 22% of the population
Future studies should investigate if there is an increase in mitochondrial turnover or a Mitochondrial Content in Frail/Prefrail Women shift in quality control in leucine supplemented pre/frail elderly women who undergo 12 weeks of resistance training (RT)
calcium retention capacity (CRC) did not differ over time or between groups, and no interaction effects were observed normalized to bundle wet weight (Ala: n = 6, Leu n = 5) (Figure 5B) or mitochondrial content (VDAC, Ala: n = 5, Leu n = 4) (Figure 5C). It is currently unknown if mitochondrial functioning can be improved by resistance training in combination with leucine supplementation in women experiencing the clinical entity of frailty or pre-frailty
Summary
The World Health Organization has predicted that globally, by 2050 those over 60 years old will double from about 11 to 22% of the population. Mitochondria appear to be central to many detrimental age-related physiological changes Both mitochondrial quality control (mitophagy and biogenesis), abundance, and function [13,14,15,16] have been shown to decline with aging. This is not always observed [14, 16,17,18,19] and to respiratory capacity in our aforementioned study [8], many of these declines are thought to be attributed to lower mitochondrial abundance in older persons, likely attributed to increased sedentariness (as opposed to an inherent change with aging) [15, 20, 21]. Leucine (Leu) can alter mitochondrial content in myocytes, while resistance training (RT) is the strongest stimulus to counteract sarcopenia and may enhance mitochondrial biogenesis
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