Longitudinal analysis of early stage sarcopenia in aging rhesus monkeys

Abstract

We present a longitudinal study using the rhesus monkey to determine biochemical and histological changes in vastus lateralis (VL) muscle fibers and whether these changes correlate with muscle mass loss. Dual-energy X-ray absorptiometry (DXA) was used to determine body weight, body fat and to estimate upper leg muscle mass in 12 adult male rhesus monkeys over 12 years. Muscle mass (MM) was evaluated at years 6, 9 and 12 of the study. Concurrently, VL muscle biopsy samples were collected. Muscle tissue was sectioned, stained and individual muscle fibers were analyzed for fiber type, cross-sectional area (CSA) and mitochondrial electron transport system (ETS) enzyme abnormalities. The animals' body weight did not change over time, however a significant increase in DXA-measured percent body fat was observed. Significant MM loss occurred in the upper leg over 12 years. A reduction in muscle fiber CSA significantly contributed to the MM loss observed in the VL of middle-aged rhesus monkeys. An age-dependent increase in muscle fibers developing mitochondrial enzyme abnormalities due to mitochondrial DNA deletion mutations was observed. The longitudinal approach of this study demonstrated that significant muscle changes occurred during middle age in a cohort of aging rhesus monkeys.

Figure 1

ETS abnormal muscle fiber from a 21y male rhesus monkey. Consecutive slide sections stained for a) COX activity, b) SDH activity and c) dual stained for COX and SDH. Note the lack of COX activity in panel (a), hyper-reactivity for SDH in panel (b) and the characteristic blue against a brown background for dual stained sections. Black bar represents 50μm.

Figure 2

Longitudinal analyses of VL muscle from 12 aging rhesus monkeys using three time points over 6 years. Panel a) upper leg muscle mass loss, b) Type II fiber cross-sectional area and c) percentage of muscle fibers in 2000μm of tissue that were ETS abnormal. Connected dots represent the same animal over time, like colored lines represent the same animal in each panel.

Figure 3

The distribution of the minimum cross-sectional area ratio for ETS normal and ETS abnormal muscle fibers.