Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys - PubMed (original) (raw)

Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys

Susan H McKiernan et al. Exp Gerontol. 2012 Mar.

Abstract

We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between ~16 and ~22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (~17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at ~27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was ~1.6 fold greater in VL from CR animals compared to Control animals at ~27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETS(ab)), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETS(ab) fiber CSA and determined that CR fibers respond differently to the challenge of mitochondrial deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals.

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Figures

Figure 1

Figure 1

Body and VL muscle composition of aged (~27 y) rhesus monkeys. Vertical bars represent the mean values for control (black) and restricted (white) and small square boxes represent individual monkeys: a). body weight, p=0.035; b). body fat, p = 0.038; c). percent upper leg muscle mass expressed as a proportion of estimated upper leg mass at ~27 years of age over maximum upper leg muscle mass observed, p = 0.015); d). percentage of Type I muscle fibers, p = 0.02; e). Type I fiber cross-sectional area (CSA), p < 0.01 and f). Type II fiber CSA, p = 0.70)

Figure 2

Figure 2

Masson’s trichrome stain for collagen on aged rhesus monkeys’ VL. Muscle stains red, collagen stains blue. Scanned images (2×) and close ups (20×).

Figure 3

Figure 3

Histogram of the frequency of normal and ETSab abnormal muscle fibers based on minimum cross-sectional area (CSA) ratio (the proportion between the minimum CSA of a fiber within the ETSab region and the mean CSA of the normal region of the fiber). Significant differences in CSA ratio distributions were observed between Control ETSab fibers and CR ETSab fibers (p = 0.022) and between CR normal fibers and CR ETSab fibers (p < 0.001).

Figure 4

Figure 4

Longitudinal analysis of Control and CR rhesus monkey VL muscle after an average of 17 years in the study. a). Upper leg muscle mass / maximum upper leg muscle mass. Both Control (n=9) and CR (n=11) undergo significant declines with age (p < 0.001), CR were significantly higher overall (p = 0.04) and Controls have a significantly sharper rate of loss compared to Controls (p < 0.001); b). Type II fiber CSA. Significant reduction in Type II fiber CSA in Control VL (n=8) occurs between ~16- and ~22-years of age, CR VL (n=10) Type II fiber CSA is relatively constant between the same years and begins to decline at ~27 years of age, Type II fibers from Controls have a significantly different trend for age-dependent atrophy compared to CR (p = 0.04); c). VL Type I fiber CSA significantly increased with age in both Control (n=8) and CR (n=10; p < 0.001), Type I fiber CSA of CR monkeys was significantly higher than Control (p < 0.001) and the rate of increase was significantly higher in CR (p < 0.001) and d). Percentage of ETSab fibers in 2000µm of VL tissue. A significant increase with age was observed in both Control (n=8) and CR (n=11). Graphs represent data accumulated between years 6 and 19 of the CR study with animals between the ages of ~16y and ~27y.

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