Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion

Abstract

Purpose: Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men.

Procedures: We performed a cross-sectional, retrospective study comparing in vivo post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22±1 y) and 72 older (75±1 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22±1 y) and 40 older (74±1 y) men.

Findings: Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion.

Conclusions: Aging is associated with the development of muscle anabolic inflexibility which represents a key physiological mechanism underpinning sarcopenia.

Fig 1. Fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[ring-²H₅] phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (n = 34 young and n = 72 elderly) and following the ingestion of 20 g protein (post-prandial; n = 35 young and n = 40 elderly).

Data were analyzed with multiple unpaired t-tests. Significantly different between corresponding post-absorptive and post-prandial values = ** (P<0.01), *** (P<0.001). Significantly different compared to corresponding values in the young = †† (P<0.01).

Fig 2. Fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[ring-²H₅] phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (n = 34 young and n = 72 elderly) and following the ingestion of 20 g protein (post-prandial; n = 35 young and n = 40 elderly.

Delta increases from post-absorptive to post-prandial were analyzed between groups using an unpaired t-test (significantly different; P<0.01). Individual responses are reported in the inset figure only in those subjects for whom post-absorptive and post-prandial muscle protein synthesis rates were assessed within the same experiment (n = 55 [22 young and 23 elderly]).

Fig 3. Graphical representation of the individual values for fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[ring-²H₅]phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (n = 34 young and n = 72 elderly) and following the ingestion of 20 g protein (post-prandial; n = 35 young and n = 40 elderly).

Fig 4. Correlation between post-absorptive fractional mixed muscle protein synthesis rates (FSR) and the delta increase in FSR following the ingestion dietary protein (post-prandial) in healthy young (n = 22) and elderly (n = 68) men.

Data were analyzed with 2-tailed tests of significance by using Pearson's correlation coefficients.