Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle

Abstract

The loss of skeletal muscle size and function with aging and sarcopenia may be related, in part, to an age-related muscle protein synthesis impairment. In this review, we discuss to what extent aging affects skeletal muscle protein synthesis and how nutrition and exercise can be used strategically to overcome age-related protein synthesis impairments and slow the progression of sarcopenia.

Conflict of interest statement

The authors do not have any conflicts of interest to declare.

Figures

Figure 1

Simplified schematic of the proposed cellular mechanisms regulating skeletal muscle protein synthesis in response to amino acids, insulin, and exercise. 4E-BP1, 4E binding protein 1; Akt, protein kinase B; BCAA, branch chain amino acids; eEF2, eukaryotic elongation factor 2; eIF4F, eukaryotic initiation factor 4F; Gln, glutamine; IRS-1, insulin receptor substrate 1; LAT1, L-type amino acid transporter 1; mTORC1, mammalian target of rapamycin complex 1; PA, phosphatidic acid; Rag, Ras-related GTPase; rpS6, ribosomal protein S6; S6K1, p70 ribosomal S6 kinase 1; SNAT2, sodium-coupled neutral amino acid transporter 2

Figure 2

Schematic representing many key factors thought to contribute to sarcopenia. These factors include: anabolic resistance (i.e., impairments in muscle protein synthesis), inactivity, insulin resistance, the loss of motor units, injury and illness (i.e., hospitalization), chronic inflammation, DNA damage, increased oxidative stress, changes in hormonal milieu, and a reduction in satellite cells. We hypothesize that strategic exercise and nutritional interventions can slow the progression of sarcopenia due to their ability to overcome anabolic impairments and attenuate the impact of several other contributing factors. Further, it is likely that sarcopenia itself contributes to, and/or accelerates the impact of these factors on skeletal muscle mass and function (represented by the double arrows).

Figure 3

The relationship between skeletal muscle protein synthesis (A) and blood flow (B) during a local insulin infusion. The ability for insulin to stimulate skeletal muscle protein synthesis requires an increase in muscle blood flow. The resistance of muscle protein synthesis to the anabolic actions of insulin in the elderly may be due to the inability for insulin to increase blood flow. This resistance to insulin in older adults can be overcome with prior aerobic exercise. Basal, fasted state (27); Insulin, postprandial insulin levels (27); Supra Insulin, supraphysiological insulin levels (12); Insulin + L-NMMA, simultaneous infusion of NG-monomethyl-L-arginine and insulin to inhibit the increase in blood flow (32); Insulin + SNP, simultaneous infusion of sodium nitroprusside and insulin to increase blood flow (33); Aer Ex + Insulin, aerobic exercise performed the night prior to an insulin infusion (postprandial level) (13). *Different from basal in respective study, p

Figure 4

The response of skeletal muscle protein synthesis to resistance exercise without nutrition (RE Only) (11) and resistance exercise followed by essential amino acid (RE+EAA) ingestion 1 hour after exercise (9) in young and older adults. Aging is associated with an impaired skeletal muscle protein synthesis response to RE only, however, this impairment is overcome with post exercise nutrient ingesting. Further, nutrient ingestion following resistance exercise produces and additive increase in skeletal muscle protein synthesis in both young and older adults. *Different from basal in respective study, p#Different from older in respective study, p<0.05.