The Ageing Bodybuilder’s Dilemma

Muscle Growth, Living Longer & Branched-Chain Amino Acids

Why do bodybuilders get excited when they hear the term “branched-chain amino acids”? Well, it’s to do with their role in kick-starting protein synthesis: crucial for growing bigger muscles. A key factor involved in the regulation of protein synthesis for muscle growth, repair and recovery is something known as mTOR [1]. Branched-chain amino acids (BCAAs) have a role in activating this enzyme, and this explains why gym-goers blow all their pocket money on BCAA supplements. However, whilst mTOR is a bodybuilder’s best friend, scientists whose careers are spent trying to solve the problem of ageing approach the enzyme with caution, as it might also be involved in cellular ageing. On the one hand, we want mTOR switched “on” for muscle protein synthesis (MPS), but on the other, we might be wise to have it switched “off” to delay the ageing process. As someone who’s been bodybuilding since his late teens, who's now reached his early 50s and thinks he’s Peter Pan, I'm presented with a bit of a dilemma. Should I be focusing on building muscle or should I be doing all I can to slow the inevitable process of ageing?

Muscle Protein Synthesis vs. Longevity

Protein has numerous roles in the body, one of which is maintaining, repairing and building muscle. Protein molecules vary in structure and length and are made up of amino acids, and there are hundreds of different amino acids in nature. Twenty are involved in the first steps of protein synthesis – known as proteinogenic amino acids – nine of which can’t be created from others so are known as essential amino acids (EAAs) and are found in varying proportions in protein-rich foods.

Protein synthesis is where tissues, such as muscle, skin, enzymes, some hormones, neurotransmitters and immune factors, are created from amino acids. Their original structure is created from the 20 proteinogenic amino acids, with others incorporated during or after the process. If you don’t consume a good amount of EAA-rich protein, less crucial tissues are broken down to prioritise keeping us alive. The immune system, for instance, steals amino acids from muscle tissue: a bodybuilder’s worst nightmare! This is why protein malnutrition includes fatigue, muscle wasting, broken skin and a compromised immune system. Three of the EAAs are classed as branched-chain amino acids because of their structure. These are leucine, isoleucine and valine and are present in high concentrations in muscle tissue, partly explaining why they’re worshipped by strength athletes. BCAAs also have other roles relating to exercise: isoleucine, for example, helps to increase glucose uptake by cells increasing their energy during activity [2]. But the main reason for all the interest in BCAAs is that they are key in controlling the turning on of MPS. According to the “leucine trigger hypothesis”, the amount of leucine in a meal dictates the rate of MPS by activating mTOR, and 2-3g is enough to kick-start it [3]. [4]. (Isoleucine and valine also activate mTOR, but leucine is considerably more potent [5].)

mTOR – or mammalian target of rapamycin – is, strictly speaking, an enzyme complex, though it’s commonly referred to as a single enzyme. When the concentration of leucine reaches a certain level, the mTOR “switch” is turned on, initiating MPS. As leucine and the other BCAAs are abundant in high-protein foods, MPS is triggered following a protein-rich meal. More protein synthesis equals bigger muscles equals happy bodybuilders!

The benefit extends to helping to maintain muscle while following a weight loss regimen, and supplementary leucine has been shown to help increase strength and performance, especially in combination with resistance training [6]. A recently published meta-analysis indicated that higher intakes of leucine around the time of resistance exercise were strongly associated with higher post-exercise MPS in older people, but not in younger adults. Based on prior evidence, the leucine trigger hypothesis may only apply to when protein supplements or BCAA supplements are consumed without the presence of other foods and nutrients [7]. The amount of leucine required to trigger MPS should be easily met when a meal or snack containing 20g of high-quality protein is consumed. Despite what clever marketers would have us think, amino acid supplements are rarely necessary. However, under conditions where an adequate protein intake is at risk, such as during a calorie restriction or when following an extreme plant-based diet, there may be a role for BCAA or leucine supplementation. There might be other benefits from additional BCAAs: supplementing with leucine has been associated with a lowering of total and LDL cholesterol levels [8], hinting at the possibility of benefits to cardiovascular health. Moreover, an adequate pool of leucine may also help preserve muscle mass during the ageing process, and an extended period of mTOR inactivity results in muscle wasting along with reduced immune activity. This partly explains the loss of muscle mass and tiredness that people experience in advanced wasting diseases, such as the latter stages of AIDS and cancer cachexia.

However, although an active mTOR is required for muscle preservation, when it’s inactive, cells divide less and reuse substrates and old cellular components to maintain energy, extending their survival [9]. From an evolutionary perspective, this makes sense: when there was little food available, our ancestors were forced to sustain themselves on meagre protein rations. With their mTOR shut down, they were able to survive for longer. For this reason, some researchers claim that fasting for extended periods may help to support longevity by delaying the ageing process. The rationale makes sense: an inactive mTOR helps to prolong the lifespan of cells, and subsequently, ourselves [10]. The theory that an inactive mTOR through fasting aids longevity is still relatively new, and, consequently, the science is still some way off being considered strong.

Bodybuilding Pensioners

Do we want mTOR to be “on”? In theory, this would help to keep our muscles strong, something that’s crucial to prevent degeneration as we age; after all, slowing muscle tissue breakdown helps us live better for longer. Or should mTOR be “off”, in order to help our cells survive for longer and, hopefully, extend our lives? Fortunately, there’s a solution to this dilemma. Firstly, don’t overeat: stick to only consuming what you need to fuel your lifestyle and workouts. Secondly, include reasonable periods where you completely refrain from eating. You already fast for several hours while you’re asleep, so why not extend this to a minimum of 12 hours? Many athletes successfully manage 16 hours or more per 24-hour period, ensuring they consume larger portions of food in the remaining window. Although current science is on the fence as to whether intermittent fasting helps cognition and focus, and whether it helps with weight loss is a particular area of controversy, there may be benefits to our health in other ways, such as possibly promoting longevity. During non-fasting periods, have a good intake of protein-rich foods at your meals; if you’re a bodybuilder, have a little more. If you do this, it’s unlikely you’ll need to spend your hard-earned cash on additional BCAA supplements.

Notes & References:
1. (a) Kim, D. H. et al. (2002) ‘mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex That Signals to the Cell Growth Machinery’, Cell, 110(2), 163-75; (b) Wipperman, M. F. et al. (2019) ‘Mammalian Target of Rapamycin: A Metabolic Rheostat for Regulating Adipose Tissue Function and Cardiovascular Health’, American Journal of Pathology, 189(3), 492-501.
2. Doi, M. et al. (2003) ‘Isoleucine, a Potent Plasma Glucose-Lowering Amino Acid, Stimulates Glucose Uptake in C2C12 Myotubes’, Biochemical and Biophysical Research Communications, 312(4), 1111-7.
3. (a) Bauer, J. et al. (2013) ‘Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper from the PROT-AGE Study Group’, Journal of the American Medical Directors Association, 14(8), 542-59; (b) Layman, D. K. et al. (2015) ‘Defining Meal Requirements for Protein to Optimize Metabolic Roles of Amino Acids’, American Journal of Clinical Nutrition, 101(6), 1330S-8S; (c) Phillips, S. M. (2016) ‘The Impact of Protein Quality on the Promotion of Resistance Exercise-Induced Changes in Muscle Mass’, Nutrition & Metabolism, 13, 64; (d) Zaromskyte, G. et al. (2021) ‘Evaluating the Leucine Trigger Hypothesis to Explain the Post-prandial Regulation of Muscle Protein Synthesis in Young and Older Adults: A Systematic Review’, Frontiers in Nutrition, 8, 685165.
4. (a) Anthony, J. C. et al. (2000) ‘Orally Administered Leucine Stimulates Protein Synthesis in Skeletal Muscle of Postabsorptive Rats in Association with Increased eIF4F Formation’, Journal of Nutrition, 130(2), 139-45; (b) Anthony, J. C. et al. (2000) ‘Leucine Stimulates Translation Initiation in Skeletal Muscle of Postabsorptive Rats via a Rapamycin-Sensitive Pathway’, Journal of Nutrition, 130(10), 2413-9; (c) Blomstrand, E. et al. (2006) ‘Branched-Chain Amino Acids Activate Key Enzymes in Protein Synthesis After Physical Exercise’, Journal of Nutrition, 136(S1), 269S-73S.
5. ibid (4c).
6. (a) Anthony, J. C. et al. (1999) ‘Leucine Supplementation Enhances Skeletal Muscle Recovery in Rats Following Exercise’, Journal of Nutrition, 129(6), 1102-6; (b) Tipton, K. D. et al. (2001) ‘Timing of Amino Acid-Carbohydrate Ingestion Alters Anabolic Response of Muscle to Resistance Exercise’, American Journal of Physiology: Endocrinology and Metabolism, 281(2), E197-206; (c) Norton, L. E. et al. (2006) ‘Leucine Regulates Translation Initiation of Protein Synthesis in Skeletal Muscle After Exercise’, Journal of Nutrition, 136(2), 533S-7S; (d) Tipton, K. D. et al. (2007) ‘Stimulation of Net Muscle Protein Synthesis by Whey Protein Ingestion Before and After Exercise’, American Journal of Physiology: Endocrinology and Metabolism, 292(1), E71-6; (e) Ispoglou, T. et al. (2011) ‘Daily L-Leucine Supplementation in Novice Trainees During a 12-Week Weight Training Program’, International Journal of Sports Physiology and Performance, 6(1), 38-50; (f) ibid (3b).
7. Wilkinson, K. et al. (2023) ‘Association of Postprandial Postexercise Muscle Protein Synthesis Rates with Dietary Leucine: A Systematic Review’, Physiological Reports, 11(15), e15775.
8. (a) Zhang, Y. et al. (2007) ‘Increasing Dietary Leucine Intake Reduces Diet-Induced Obesity and Improves Glucose and Cholesterol Metabolism in Mice via Multimechanisms’, Diabetes, 56, 1647-54; (b) Zhao, Y. et al. (2016) ‘Leucine Supplementation via Drinking Water Reduces Atherosclerotic Lesions in apoE Null Mice’, Nature, 37, 196-203.
9. Sinclair, D. A. and LaPlante, M. D. (2019) Lifespan: Why We Age—and Why We Don’t Have To, London: Harper Collins, p25.
10. (a) Perluigi, M. et al. (2015) ‘mTOR Signalling in Ageing and Neurodegeneration: At the Crossroad Between Metabolism Dysfunction and Impairment of Autophagy’, Neurobiology of Disease, 84, 39-49; (b) Kennedy, B. K. and Lamming, D. W. (2016) ‘The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging’, Cell Metabolism, 23(6), 990-1003; (c) ibid (9), p25.