Usefulness of preclinical models for assessing the efficacy of late-life interventions for sarcopenia

Abstract

Caloric restriction and physical exercise have proven beneficial against age-associated changes in body composition and declining physical performance; however, little is known regarding what benefit these interventions might have when initiated late in life. The study of mimetics of diet and exercise and the combination thereof may provide additional treatments for a vulnerable elderly population; however, how and when to initiate such interventions requires consideration in developing the most safe and efficacious treatment strategies. In this review, we focus on preclinical late-life intervention studies, which assess the relationship between physical function, sarcopenia, and body composition. We provide a conceptual framework for the ever-changing definition of sarcopenia and a rationale for the use of an appropriate rodent model of this condition. We finish by providing our perspective regarding the implications of this body of work and future areas of research that may also contribute to the ultimate goal of extending healthspan.

Figure 1.

Least square means of the swimming speed procedures, over a 6-month time period (24–30 months). Longevity was significantly predicted by higher baseline swim speed (hazard ratio 0.88 for 1 cm/s increase; 95% confidence interval 0.81–0.97; p = .009),

Figure 2.

Latency to fall (a) from an incline plane in 24-month-old F344BN male rats that were wheel running for 2 weeks (n = 20) or were sedentary (n = 19). *p = .04 for difference from a wheel-running group by t test. (b) Correlation between latency to fall from an incline plane and body weight, p = .037, r² = .112.

Figure 3.

Young and old F344BN rats were fed rapamycin for 3 weeks or were given a regimen of intermittent (every other day) calorie restriction (IF). IF- and rapamycin-treated animals lost approximately 15% of their body weight relative to controls. Moreover, the young IF animals lost more weight than their rapamycin-fed counterparts (lower panel). There was an effect of age on the memory test (upper right); however, rapamycin had no impact on cognitive function, although physical activity was increased with treatment, regardless of age (*all ps < .05).

Figure 4.

Four weeks of low-intensity exercise (12 cm/s; 10 combined with low-dose enalapril treatment (20 mg/kg/d) administered to 24-month-old male F344BN rats results in additional weight loss and greater endurance relative to enalapril treatment alone (*p < .05).