I am afraid it has been a long time since my last blog post. I have been busy at work, though I have also made some progress in recovering fitness following my bicycle accident last summer. Before the accident I had been planning a ’heptathlon’ of events, including running, jumping, swimming, cycling, lifting, and balancing, for the week of my seventieth birthday in late March of this year. Following the accident it appeared that the goals I had set were totally out of reach. In light of my rather slow recovery in the latter part of 2015, at the beginning of 2016 I had reset my targets for each event. However, although the torn ligaments in my left knee are still only partially healed, I have made substantial progress in the past 2 months and am now hopeful I will achieve my original targets in at least several of the events. I have had fun teaching myself the Fosbury Flop – despite having to adjust to taking-off from my non-preferred leg because of the damage to my left knee. Even when taking-off from the right leg I need to be very careful about foot placement during the run-up. I have also taken the opportunity to learn the rudiments of a proper front-crawl swimming technique. But I will defer a more detailed account of my birthday heptathlon for a future post.
Now it is time to return to the issue of longevity of long distance runners. In previous posts I had addressed some of the basic science and had also examined the evidence regarding cardiac outcomes. In this post I will address the issue of deterioration of skeletal muscle, and what can be done to minimise it.
When a muscle is not used, signalling molecules within the muscle fibre initiate a sequence of events resulting in cessation of protein synthesis and increase in protein degradation. In a world where cars and other mechanical devices have greatly reduced the need to use muscles vigorously, disuse is a major contributor to the loss of muscle and function with age, a condition known as sarcopenia. However, even among those who continue to use their muscles, sarcopenia can only be held at bay, perhaps for decades, but eventually age extracts its remorseless toll. For the general population, there is a simple public health message: exercise, along with a diet that includes adequate intake of protein and other nutrients, can slow the progression of sarcopenia.
However for the dedicated athlete the message is a little more complex. Running itself can damage muscle both by direct mechanical trauma and also my biochemical trauma. The question of what type and amount of exercise is most effective for ensuring longevity as a runner is challenging. We should start by examining the mechanisms by which running itself might actually damage muscle.
Mechanical damage in skeletal muscle
The eccentric contraction of leg muscles at footfall results in stresses that pull muscle fibres asunder, especially at points where the contractile actin molecules attach to the structural framework of the muscle fibre. This damage leads to an inflammatory response, in which fluid accumulates in the muscle, bringing with it the cells and nutrients required for repair and subsequent scavenging of debris. In the short term (over a time scale of hours) there is often a measurable increase in muscle size. As the repair proceeds a supportive mesh of collagen fibres are laid down. Initially this mesh is likely to prove a minor obstruction to smooth movement of the fibres.
Restricted movement leads to the accumulation of more fibre. Here is a quite intriguing short video by Gil Hedley about the fuzz that accumulates around muscle fibres that have become immobilised (illustrated in a cadaver, so do not watch it is you are squeamish). It is crucial to ensure tissues are mobilised during the recovery from a hard training session. While the most certain way to build up restrictive fibrous fuzz between muscles surfaces leading to restricted mobility in old age is a very sedentary lifestyle, but it is likely that years of training sessions which produce micro-trauma, without appropriate fuzz-clearing recovery is not much better. It makes sense to me that a systematic strategy for mobilisation during recovery – be it massage, stretching or gentle movement – is crucial for longevity as an athlete. I have ready access to an elliptical cross trainer and my own preference is a relaxed elliptical session to maintain mobility of the fibres within my muscles. In addition I apply cross fibre friction massage (usually using my thumb) at focal sites of tenderness on tendons and other connective tissues to disrupt the formation of fuzz.
Perhaps more insidiously, the very process that generates energy to fuel muscle contraction produces damage. Muscles generate energy by burning fuel, mainly glucose or fats, to generate the energy rich molecule, adenosine triphosphate (ATP). The energy contained in the phosphate bonds of ATP is the immediate source of energy the drives the ratchetting of actin over myosin molecules to produce muscle contraction. A modest amount of ATP is produced during the early steps in metabolism of glucose via anaerobic glycolysis. Glycolysis converts glucose to pyruvate which is then converted to acetyl CoA provided oxygen is available. The early steps of fat metabolism also generate acetylCoA. In the presence of oxygen, acetylCoA is oxidised in mitochondria, via the Krebs (citric acid) cycle producing carbon dioxide and various molecules (such as NADH) that can act as electron donors. The most bountiful production of ATP during process of energy metabolism arises during the final stage: the electron transport chain.
In this final stage, electrons are transported along a chain of molecules embedded in the inner membrane of the mitochondria. In association with this transport of electrons, the charged protons that remain when an electron is removed from hydrogen, are transported into the space between the inner and outer membranes of the mitochondrion, setting up a voltage gradient, as depicted in figure 1. This voltage gradient drives the protons back into the inner compartment of the mitochondrion via an ion channel though the enzyme, ATP synthase, embedded in the inner membrane, delivering the energy required to produce ATP. However, this energetic process is almost literally playing with fire. In the process, electrons are stripped off oxygen atoms producing highly reactive positively charged oxygen ions that can leak out of the mitochondria and avidly bind to other molecules, producing irreversible oxidative damage.
Mitochondria become damaged; they typically have a half-life in the range 3 to 10 days. They must be replaced and the debris removed. Healthy aging requires the maintenance of efficient replacement, which is turn is dependent on the expression of the relevant genes as described in my recent post, and effective scavenging of debris. Damaged mitochondrial membranes are leakier, and are therefore more prone to release reactive oxygen ions and create greater damage within cells. In the elderly, mitochondria tend to be leakier.
There are also other metabolic mechanisms that result in exercise induced muscle damage. Although the details of the mechanism are debatable, exercising to the point where muscle glycogen store is seriously depleted also has the potential for damage. It is possible that glycogen depletion leads to serious depletion of ATP which is essential for most energy demanding intra-cellular processes, including the pumping of calcium. Calcium is released during muscle contraction and accumulates to damaging levels unless removed by ATP-fuelled pumping across the sarcolemma, the membrane that encloses each muscle cell membrane. It is plausible that this is a major mechanism of muscle damage during the later stages of a marathon.
Minimizing damage from mechanical trauma
Although the inflammation induced by micro-trauma is a part of the mechanism by which the muscle is repaired and strengthened, at least in the elderly and perhaps in all athletes, it is almost certainly desirable to avoid excessive micro-trauma and subsequent accumulation of residual fibrous tissue as a by-product of the repair process. A sudden increase in training volume or intensity leads to Delayed Onset Muscle Soreness (DOMS) whereas more gradual increase is associated with minimal DOMS indicates that the first. This is a manifestation of the repeated bout effect, a protective adaptation against “maximal” eccentric contractions that is induced by submaximal eccentric contractions or a relatively small number of eccentric contractions. Perhaps the most important strategy for minimising accumulation of muscle damage with age is ensuring a gradual increase in training volume and intensity. In a recent review, Nosaka and Aoki concluded that the magnitude of muscle damage can be attenuated by the use of the repeated bout effect more efficiently than any other prophylactic interventions.
While acute inflammation is largely a beneficial process that is essential for repair of tissues, if inflammation is sustained it becomes chronic, leading to long-lasting and perhaps permanent impairment of function. Therefore, adequate recovery after demanding training sessions and races is crucial. Recovery does not necessarily demand absolute rest, as mobilization of tissues is important to minimise build of fibrous tissue – the fuzz described graphically in the video by Gil Hedley. The mobilization should be active enough to break down mis-oriented collagen fibres and to encourage blood flow, but not so vigorous as to cause new trauma. I favour low-impact cross training for this purpose.
For fast running, a strong push off from stance, mediated by an eccentric contraction is essential (as illustrated by Peter Weyand and colleagues). However, for a distance runner the goal must be to achieve peak efficiency in a manner that does as little damage to muscle s as possible. In general, increasing cadence reduced impact forces, and for many recreational athletes, an increase in cadence actually improves efficiency. As I have discussed elsewhere, there is a limit to the benefits of increasing cadence. Nonetheless, for the elderly runner, during training it is probably advisable to aim for a short stride with relatively high cadence during long runs. This is a key feature of the training of Ed Whitlock.
Protein and amino acids
Repair requires amino acids which are the building blocks of the proteins that required to rebuild the components of muscle fibres. The presence of amino acids in the blood stream acts as a stimulus to protein synthesis. Furthermore certain amino acids are critical, especially branched chain amino acids, which are essential in the sense that they cannot be synthesized within the body and therefore must be ingested. Howatson and colleagues demonstrated that following a session in which muscles were damaged by eccentric contraction during drop-jumps, 12 days of supplementation with branched chain amino acids produced significantly greater reduction muscle soreness and in levels of creatinine kinase in the blood (a measure of muscle damage) and significantly greater recovery of muscle strength than observed in a control group who received placebo.
Another useful strategy for minimising muscle trauma is low-impact cross training. I personally do about 30% of my training on the elliptical cross trainer. Some of these sessions are recovery sessions, but I also do many of my high intensity sessions on the cross trainer as this allows me to increase aerobic fitness with minimal muscle trauma.
It might be expected that resistance training would enhance the longevity of a distance runner by virtue of delaying sarcopenia and increasing resistance to mechanical trauma. However until recently the picture has been confusing. Skeletal muscles exhibit quite different changes in physiology and metabolism in response to resistance training compared with endurance training. Endurance training promotes a development of type 1 (slow twitch fibres) at the expense of type 2 (fast twitch) fibres, and increases the number of mitochondria, but does not produce muscle growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in muscle growth, achieved by fusion of satellite cells (a type of stem cell found in muscle) with existing muscle fibres. These differences in response to different types of exercise reflect different signalling processes within the muscle cells.
In a seminal study of isolated rat muscle, Atherton and colleagues demonstrated that low frequency simulation switches on a signalling pathway known as the AMPK-PGC-1α signalling pathway, which promotes aerobic metabolism and leads to the changes typical of endurance training, whereas high frequency stimulation which mimics the effects of resistance training, selectively activates the PKB-TSC2-mTOR signalling cascade causing changes consistent with increased protein synthesis and muscle growth. mTOR is a cardinal growth regulator that is switched on by various nutritional and environmental cues.
While the observation of mTOR activation provides a plausible mechanism by which resistance training increases muscle growth, it was at first unclear whether or not this would promote increased or decreased longevity. mTOR has opposite effects to another regulator, myostatin, which switches off muscle growth. Early evidence indicated that myostatin acts to increase longevity. This evidence was consistent with the puzzling but robust evidence that calorie restriction promotes longevity in laboratory animals. However more recent studies have demonstrated that the effects of myostatin are more complex than initially believed. In fact, there is growing evidence that activation of mTOR and associated muscle growth is associated with longevity.
For example, Melov and colleagues examined the effect of six months of regular resistance exercise in a group of elderly participants. At baseline the elderly participants were 59% weaker than a young adult control group, but after the six months of resistance exercise their strength increased significantly such that they were only 38% lower than the young adults. The investigators also examined the degree of expression of genes before and after the 6 months of resistance training. At baseline there were a large number of genes that showed different levels of expression in the elderly group, but following exercise training the expression of most of the relevant genes returned to the levels observed in the young adults. Thus, resistance training not only achieves quite different changes in muscles compared with the effects of endurance training, but these changes appear to reverse features of age-related degeneration. In a recent review, Sakuma and Yamaguchi concluded that resistance training in combination with amino acid-containing nutrition appears to be the best candidate to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness.
Stretching and massage
Despite the popularity of stretching, the evidence of benefits is minimal. It is probable that static stretching of cold muscles does more harm than good. However, as mentioned above, it makes sense to me that a systematic strategy for mobilisation during recovery after racing and training is worthwhile. Furthermore, there is growing evidence that massage can be helpful. For example, a study by Crane and colleagues at McMaster University in Ontario demonstrated that massage therapy attenuates inflammatory signalling after exercise-induced muscle damage. Studies in rabbits, reviewed by Alex Hutchinson, indicate that massage promotes muscle repair, and blood vessel formation, possibly by a mechanism initiated by stretch-sensitive receptors in muscles .
Minimizing damage from biochemical trauma
There is little direct evidence of effective strategies for minimising biochemical trauma, but our current understanding of mechanisms suggests several plausible approaches.
In light of the fact that damaged mitochondria are prone to leak potentially damaging reactive oxygen ions generated as a by-product of the electron transport that generates copious ATP, maintaining mitochondria is good condition is crucial for minimising damage. The maintenance of a healthy stock of mitochondria depends on a balance between the genesis of new mitochondria (biogenesis) and the removal of old mitochondria (mitophagy). The complex set of intra-cellular signalling processes that regulate this balance is described in a review by Palikaras. The signalling molecule, PGC-1α, is the core regulator of mitochondrial biogenesis. Signalling via PGC-1α is promoted by aerobic exercise. One of the key benefits of relatively low intensity aerobic exercise is the promotion of mitochondrial biogenesis with relatively little risk of further damage.
There are other potential benefits of low intensity training. The evidence that impaired ability to pump the calcium released during muscle contraction back into muscle cells when glycogen is seriously depleted indicates that sustained running in the upper aerobic zone is potentially harmful. One way of minimising glycogen depletion is enhancing capacity for fat metabolism. Perhaps relatively large volume low intensity running is the safest way to achieve this.
It should however be noted that the first stage of metabolism of fats leading to the production of acetyl CoA (beta-oxidation) generates less ATP per molecule of acetyl CoA produced than the corresponding stage of glucose metabolism (glycolysis), more oxygen must be consumed to generate a given amount of energy from fat than from glucose. Thus, fat metabolism actually makes relatively greater demands on the citric acid cycle and the electron transport chain that glucose metabolism for a given rate of energy production. Thus, fat metabolism leads to less efficient use of oxygen and it remains unclear whether or not fat metabolism is less stressful for mitochondria overall. However, the contrast between the body’s limited store of glycogen yet abundant store of fat means that at moderate paces, ability to use a higher proportion of fat in the fuel mix would be expected to place less overall stress on the body during sustained running at such paces.
In light of the potential damage produced by excess release of calcium fron muscle cells, it is also potentially helpful to attempt to enhance the capacity for calcium ion transport back into cells. Interestingly, high intensity training (HIT) has the capacity to achieve this. In contrast to the possibility of damage from sustained upper aerobic exercise, HIT would be expected to produce surges of calcium release during the bursts of high intensity activity with an opportunity for reuptake during the recovery epochs.
Although this is speculative, I think that a polarised training program characterised by a large volume of low intensity running and a small proportion of high intensity interval running is potentially the optimum strategy for optimising longevity as a runner.
The evidence reviewed above leads to several recommendations for promoting longevity as a runner.
- Gradual increase in training volume
- Optimising cadence
- Thorough recovery after strenuous events
- Stretching and mobilization; massage
- Low impact cross training
- Low intensity running to promote both mitochondrial biogenesis and fat metabolism
- Enhancing calcium pumping by High Intensity Training
- Adequate protein intake, including adequate sources of branched chain amino acids.
So far in this series we have focussed largely on local effects in cardiac muscle and in skeletal muscle. However, there are also important mechanisms mediated by hormones and other signalling molecules in the blood stream, that play a role in damage, repair and protection. In the final post in this series we will examine these mechanisms.