Katsanos, Christos S., Hisamine Kobayashi, Melinda SheffieldMoore, Asle Aarsland, and Robert R. Wolfe. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 291: E381-E387, 2006. First published February 28, 2006 doi:10.1152/ajpendo.00488.2005.-This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of L-[ring-2 H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 Ϯ 0.005%/h; post-EAA: 0.063 Ϯ 0.007%/h) and the 41% (basal: 0.036 Ϯ 0.004%/h; post-EAA: 0.051 Ϯ 0.007%/h) Leu young groups (P Ͻ 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 Ϯ 0.003%/h; post-EAA: 0.049 Ϯ 0.006%/h; P Ͼ 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 Ϯ 0.007%/h; post-EAA: 0.056 Ϯ 0.008%/h; P Ͻ 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved (P Ͻ 0.05) in all groups, with the exception of the 26% Leu elderly group. We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects. nutrition; sarcopenia; stable isotopes MUSCLE PROTEIN METABOLISM alternates between periods of net catabolism in the postabsorptive state and net anabolism in the postprandial states, with the latter being primarily a result of changes in muscle protein synthesis (28

Essential amino acids are primarily responsible for the amino acid-induced stimulation of muscle protein anabolism in the elderly.

The data suggest that exercise and AAS together may be effective in enhancing not only muscle strength, but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women.

These data indicate that aging results in a diminished accretion of muscle proteins after ingestion of a small dose of EAAs. These findings may have practical implications with respect to the amount of protein contained in supplements given to the elderly for enhancing the stimulation of muscle protein synthesis.

No abstract

Supplementation of the diet with EAA+arginine improves lean body mass, strength and physical function compared to baseline values in glucose intolerant elderly individuals.

BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise.

PJ. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab 308: E1056-E1065, 2015. First published March 31, 2015; doi:10.1152/ajpendo.00481.2014.-Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two feeding regimes in older women (66 Ϯ 2.5 yr; n ϭ 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]. Using [ 13 C6]phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to both feeding (FED) and feeding plus exercise (FED-EX; 6 ϫ 8 knee extensions at 75% 1-repetition maximum). We also quantified plasma insulin/AA concentrations, whole leg (LBF)/muscle microvascular blood flow (MBF), and muscle anabolic signaling by phosphoimmunoblotting. Plasma insulinemia and EAA/aemia were markedly greater after WP than LEAA (P Ͻ 0.001). Neither LEAA nor WP modified LBF in response to FED or FED-EX, whereas MBF increased to a similar extent in both groups only after FED-EX (P Ͻ 0.05). In response to FED, both WP and LEAA equally stimulated MPS 0 -2 h (P Ͻ 0.05), abating thereafter (0 -4 h, P Ͼ 0.05). In contrast, after FED-EX, MPS increased at 0 -2 h and remained elevated at 0 -4 h (P Ͻ 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr 389 increased after FED-EX (2 h, P Ͻ 0.05). APS increased similarly after WP and LEAA. Older women remain subtly responsive to nutrition Ϯ exercise. Intriguingly though, bolus WP offers no trophic advantage over LEAA. skeletal muscle; blood flow; protein synthesis; aging; amino acids; exercise ILL HEALTH ASSOCIATED WITH AGING represents a major socioeconomic burden, especially given shifting demographics toward a more aged, populous world. In particular, the loss of skeletal muscle mass associated with aging, or sarcopenia, is a major clinical issue. For instance, not only are there established links between low muscle mass and all-cause mortality per se (1), but also, lower skeletal muscle mass associated with sarcopenia leads to increased frailty, risk of falls, sedentarism, poor quality of life, and prevalence of metabolic comorbidities (17, 53).The two major extrinsic influences over muscle mass are nutrition and physical activity. For example, oral intake of protein-based foods containing essential amino acids (EAA) leads to a transient (2-3 h; see Ref.2) stimulation of muscle protein synthesis (MPS) in younger men. This brief increase in MPS above postabsorptive rates serves the purpose of replenishing protein stores lost during fasting, ensuring preservation of muscle protein mass. Similarly, physical activity is a prerequisite for maintenance of a healthy muscle mass. For example, inactivity (6, 20) causes muscle atrophy by inducing "anabo...