In recent posts I have examined various the ways in which the body changes with age, with the aim of drawing some practical conclusions about lifestyle and training to maximize the chance of continuing to run well in old age. After starting with anecdotal evidence drawn for the experiences and the training of several of the world’s best elderly marathoners, and then examining some of the basic science, in the third and fourth articles in the series I addressed the effects of aging on heart muscle and on skeletal muscle.
However, the body functions as an integrated whole, due to the coordinating action of the nervous system and messenger molecules, such as hormones and cytokines, that circulate in the blood stream. In this final article in the series I plan to examine ‘whole body’ factors that play a crucial role in how well we age.
Hormones: achieving a balance between catabolism and anabolism
Catabolic hormones, such as cortisol, promote the break down of tissues and the combustion of fuel to generate energy. Anabolic hormones, including growth hormone and androgens promote the building up of tissues.
During distance running, cortisol plays an vital role in mobilising the glucose required to fuel muscle contraction, and also to supply other crucial organs, especially the brain. However, the stress of regular training tends to create sustained elevation of cortisol thereby promoting a chronic catabolic state that favours the break down body tissues and might also impair immune defences. A study by Skoluda and colleagues confirms that endurance athletes tend to have persistently high levels of cortisol. The increase is greater in those with higher training volume. Thus the regulation of cortisol is potentially of great importance, not only for ensuring that an athlete obtains benefits from training, but also for long term health
The balance between the beneficial role of short term increase in cortisol and the damaging influence of chronic elevation is illustrated in a study of distance runners by Balsalobre-Fernandez and colleagues. They measured salivary cortisol levels, neuromuscular effectiveness as indicated by counter-move jump height (CMJ) and various other measures throughout a 39 week running season.. As had been observed in previous studies, in this study CMJ was a predictor of an individual’s running performance, being highest before the season’s best and low before the season’ worst performance. On a week by week basis, high cortisol correlated positively with CMJ height, but averaged across the entire season, there was a negative correlation between cortisol and CMJ height. In the short term, high cortisol is associated with good performance but in contrast chronic cortisol elevation is likely to impair performance.
Exercise, especially resistance exercise, also stimulates the release of anabolic hormones thereby promoting repair and compensatory strengthening of damages tissues, and helping restore a healthy balance between anabolism and catabolism. With increasing age, the body becomes less responsive to anabolic stimuli and there is tendency for the balance to shift towards catabolism. Thus, for the elderly distance runner, avoiding excessive catabolism while promoting anabolism becomes important.
As illustrated in a study of older adults by Melov and colleagues, 6 months of resistance training can partially reverse muscle weakness, in parallel with a substantial reversal of the disadvantageous pattern of gene transcription and muscle protein synthesis associated with aging.
However it would be too simplistic to assume that artificially increasing the action of a specific anabolic hormone would lead to either longer life or greater longevity as a runner. In fact there is only inconsistent evidence that levels of any one anabolic hormone are predictive of life-span. The inconsistency of the evidence is probably due to the fact that hormones are subject feed-back control that moderates the effect of increase in level of a hormone, and furthermore there are complex interactions between hormones. Nonetheless, the importance of addressing the tendency towards diminished anabolism with age is confirmed by the evidence that an overall decrease in anabolic effects due to a decrease of multiple anabolic hormones leads to shorter life expectancy and greater frailty. For example, Maggio and colleagues found that low levels of multiple anabolic hormones are associated with increased and 6-year mortality in older men, while Cappola and colleagues demonstrated that multiple deficiencies in anabolic hormones were associated with increased frailty in older women.
The inadequacy of augmenting a single anabolic hormone is illustrated well by the effects of altering levels of growth hormone. Growth hormone is released by the anterior pituitary gland and acts on many tissues of the body to stimulate growth and cell regeneration. It stimulates the liver to produce a messenger molecule, IGF-1 (Insulin-Like Growth Factor, type 1) that promotes hypertrophy while decreasing the formation of harmful free radicals and inhibiting cell death and slowing the atrophy of both skeletal and heart muscle (as illustrated in the figure). It also raises the concentration of glucose and free fatty acids. These multiple apparently beneficial effects initially led to enthusiasm for growth hormone supplementation as an anti-aging treatment.
Figure: The brain integrates information from the body and the external world, and when required sends signals to the pituitary gland at the base of the brain. The pituitary releases growth hormone which has multiple effects including stimulating the liver to produce IGF-1, which in turn stimulates repair and regeneration in muscle, bone and other tissues.
However despite some evidence of apparently beneficial changes, such as increased lean body mass and bone mineral density in elderly men reported by Rudman and colleagues, several meta-analyses that assembled the overall evidence from many studies failed to find clear-cut evidence of benefit.
Further light is cast on this paradox by evidence that in several species of animals ranging from nematode worms to mice, disruption of IGF signalling actually promotes increased life-span, by increasing the activity of several genes that promote longevity. There is some evidence of similar effects in humans, especially among those reaching advanced old-age. In a study of nonagenarians, Milman and colleagues demonstrated that low IGF levels were associated with increased survival in females. Furthermore, in both males and females with a history of cancer, lower IGF-1 levels predicted longer survival. It is possible that the observed beneficial effect of low IGF-1 levels on survival in humans is at least in part due to diminished cell production in individuals susceptible to malignant proliferation.
The paradoxical benefical consequences of diminished IGF-1 provide a strong warning against a simplistic approach based on supplementation of a single anabolic hormone. Any such approach runs the risk of upsetting the balance in a finely tuned system of interacting hormone and messenger molecules. However there are many ways in which we can promote the development of a beneficial balance between anabolism and catabolism by engaging the body’s more nuanced responses. Exercise (especially resistance exercise); diet (rich in variety and with adequate protein); sleep (which promotes growth hormone release) and stress reduction (which reduces the sustained release of catabolic hormone) all shift the balance towards anabolism.
Damage produced by chronic inflammation
Inflammation is the cardinal mechanism by which the body repairs itself following injury. It is also the mechanism by which many of the beneficial effects of training are achieved. The stress of training induces microscopic trauma that triggers an inflammatory response that repairs and strengthens the body. But chronic inflammation is harmful and plays a role in many of the diseases that that become more prevalent with increasing age, including diabetes, heart disease, stroke, cancer and Alzheimer’s disease (reviewed in a readable article in U.S. News Health).
Within this series on the longevity of the long distance runner, we have already discussed the adverse effects of chronic inflammation in the heart and in skeletal muscle. While many of the manifestations of inflammation are localised in a particular tissue, inflammation is mediated by messenger molecules that circulate throughout the blood stream and thus inflammation is a ’whole body’ issue. Inadequate recovery from demanding exercise is likely to lead to circulating pro-inflammatory messenger molecules. Although it is not proven, it is plausible that circulating pro-inflammatory messengers play a role in several of the harmful conditions that occur with increased prevalence in endurance athletes, such as asthma, cardiac rhythm disturbances, and more controversially, the increased atherosclerosis observed in elderly men who have competed in multiple marathon (discussed in my previous post in 2010),.
Diet can play an important role in increasing or decreasing the risk of chronic inflammation. For example, omega-3 fatty acids tend to by anti-inflammatory while omega-6 fatty acids are pro-inflammatory. It is nonetheless important to re-iterate that inflammation has both beneficial and harmful effects, and in general, a healthy diet is a balanced diet.
As discussed in a more detail in a blog post in 2014, the three key things we can do to minimise the risk of damage are:
1) Allow adequate recovery after heavy training and racing. Studies in animals and humans demonstrate that much of the fibrosis arising from chronic inflammation, resolves during an adequate recovery period.
2) Build up training gradually. The tissue trauma that initiates the inflammatory process is less if the tissues have been strengthened by gradual adaptation. This is illustrated by the fact that DOMS is more marked if you suddenly increase training volume.
3) Consume a diet that minimises chronic inflammation. Current evidence indicates that a Mediterranean diet, in which the pro-inflammatory omega-6 fats prevalent in the Western diet are balanced by omega-3 fats from fish and/or nuts and green leafy vegetables, is a heart-healthy diet.
Protecting our DNA
While variation in genetic endowment only contributes a minor fraction to the variation in longevity between individuals, our genes nonetheless play a crucial in the functioning of the cells of our body throughout our lives. The translation and transcription of the DNA strands that carry the genetic code generates the RNA template required for building the proteins that are needed to sustain and repair bodily tissues. Furthermore, the regeneration of cells via the process of cell division requires the duplication of the DNA so that each ‘daughter’ cell has the necessary complement of DNA. Thus the protection of the integrity of our DNA throughout our life-span is essential for repair and replacement of cells.
There are three main ways in which the integrity DNA can be compromised
- Mutations, produced by radiation, environmental toxins or chance errors in duplication during cell division. Mutation change the sequence of the DNA base-pairs (A-T and G-C) thereby changing the code itself. Mutations in sperm or eggs affect subsequent generations. Mutation within other bodily cells are unlikely to have a widespread defect on the body, except in the situation where the mechanism that regulates cell division is damaged causing the affected cell becomes malignant. A healthy immune system scavenges rogue cells that threaten to become malignant. Moderate exercise and a well-balanced diet that promote a healthy balance between catabolism and anabolism help maintain a healthy immune system.
- Certain locations on DNA are prone to undergo a chemical change known as methylation, in which a methyl group (-CH3) is attached to cytosine (the letter ‘C’ in the genetic code). Although this chemical change does not change the order of the DNA base-pairs and therefore does not change the genetic code itself, it can affect the readiness with which the DNA can be transcribed to produce protein when required. DNA methylation patterns change in a systematic way with aging. Some of the variations are predictive of likelihood of dying within a given time-span. So far there is no convincing evidence that change in specific DNA methylation patterns can extend lifespan. Nonetheless, the rate of age-specific DNA methylation changes is dependent on a range of circumstances, including tissue inflammation; exposure to the stress hormone, cortisol; and nutrition. In a review of aging and DNA methylation, Jung and Pfeiffer conclude that intake of essential nutrients (including methionine, folic acid, and vitamin B12) involved in the metabolism of methyl groups, might be key factors in delaying the progressive deterioration of DNA methylation patterns, and hence may be important for healthy aging.
- Each chromosome has a protective cap known as telomere at its end, but these telomeres become shortened as a result of repeated cell duplication. When the telomeres become very short, cell division can no longer occur and tissues can no longer be regenerated. However shortening of telomeres is not irreversible. For example, Ramunos and colleagues report that RNA treatment of cultured human cells can produce lengthening of telomeres. Furthermore, Ornish and colleagues have reported evidence indicates that telomeres can be lengthened by a balanced diet, exercise and stress reduction:
Overall, the evidence indicates that a balanced diet, exercise and stress reduction can help protect of DNA. However the question of what constitutes a healthy diet remains controversial, The various different studies that have led to the conclusion that a healthy diet might protect DNA have differed in the details of the diet. Nonetheless, the main features of a healthy diet are a modest amount of each of the major macronutrients (carbohydrates fats and protein) and a plentiful supply of diverse micronutrients (vitamins and trace elements). In the elderly, utilization of dietary protein is less efficient the in the young, and a higher daily intake of protein is required
The Brain and its Mind
The forgoing discussion has emphasized the important of control of stress in promoting a healthy balance of anabolism and catabolism, minimization of chronic inflammation and protection our genes. The central controller of stress is the brain and the mind it supports.
For the athlete, perhaps that most useful way to describe the role of the brain is in terms of the central governor. The concept of the central governor was originally proposed by Tim Noakes to account for the observation that even when athletes exert themselves to their utmost, at the end-point there is still at least a small amount of energy in reserve. This is illustrated by the fact than many marathoners can muster a sprint when the end is in sight despite being unable to increase pace when there is still a mile still to run. It appears that the brain exerts a restraining influence to prevent us pushing ourselves into a dangerously stressed state. This concept of the central governor as a controller that sets a limit on performance has been controversial. An alternative view is that fatigue is determined by exhaustion of muscles rather than signals from the brain. Whether or not all aspects of the concept as proposed by Tim Noakes are accurate, there is no doubt that the brain and its mind exert a strong influence not only over athletic performance, but over many aspects of how our bodies react to challenge.
It is almost certainly misleading to envisage the central governor as a small homunculus wearing a pilots cap and googles sitting in a cockpit located near the front of the brain with hand on the throttle to determine how fast we run. In fact a network of circuits in the brain receive input from diverse regions of the body and from the external world, synthesize this mass of information and send messages not only to the muscles but to the endocrine glands that secret hormones and either directly via the nervous system or indirectly via hormones, to all organs of the body that determine how our body responds to the challenges currently facing it. The way in which the brain syntheses the sensory information is guided by past experiences and by beliefs and goals. I find it helpful to regard this network of brain circuits that integrate sensory information, past experience, belief and goals to generate messages that determine how our body responds to challenge as the central governor.
Training teaches us what we are capable of, but our beliefs also have immense capacity to influence the decisions of our central governor. The power of belief in athletic performance is well demonstrated by numerous anecdotes; not least by the way in which Roger Banister’s sub-4 minute mile opened the gate to a stream (though not a flood) of subsequent sub-4 minute miles. Belief also influences the way in which our bodies respond to training. Crum and Langer informed a group of hotel cleaners that the work they did would make them fitter. Four weeks later they had lower blood pressure, less body fat and other signs of improved fitness compared with a matched group of colleagues who had done the same work but had not been advised about the health benefits of that work. In medical practice, the placebo effect is one of the most powerful tools in the hands of a physician.
In the domain of aging, it is common to hear ‘you are only as old as you feel’. This is a truism that might ring a little hollow in the minds of aging runners who observe the almost inexorable deterioration of their performances with the passing years. However, despite the overall validity of the expectation that the passing years bring deterioration, we risk sabotaging our own prospects by accepting that year-on-year decline is an absolute certainty. I find it helpful to hold in mind the fact that Ed Whitlock failed to break 3 hours for the marathon at age 70 but achieved the time of 2:54:48 at age 73.
With regards to the effect of age on general health, the evidence from the MIDUS study (a large study of Midlife Development in the U.S.) that higher perceived control over one’s life affects the expression of genes that modulate physical health. Furthermore there appears to be a reciprocal relationship between mental and physical factors insofar as vigorous exercise promotes a sense of control over one’s life. It is plausible that the reciprocal relationship between mental and physical adaptation to aging arises from the reciprocal relationship between adaptation to stress and metabolic efficiency mediated by nervous and endocrine systems.
Despite the strong evidence that the mind can exert an influence over matter, it is a challenge to find effective ways of enhancing our ability to harness this powerful influence. My own experience has taught me that one effective approach is avoiding jumping to premature conclusions about the effects of aging, but instead examining the evidence, both scientific and anecdotal, and putting my predictions based on this evidence to the test in practice, bearing in mind that average outcome predicted for the entire population does not dictate the fate of the individual.
If we wish to maintain health in old age, and in a particular, extend our longevity as distance runners, we need to achieve an optimum balance between catabolism and anabolism; derive benefit from the repair and strengthening mediated by acute inflammation while avoiding the damage of chronic inflammation; and maintain our DNA in good condition. A balanced diet; gradual build-up of training and good recovery after intense exercise; avoidance of undue stress; and maintaining confidence that we have control over our own fate all play a role in achieving these goals.
In previous articles in this series on longevity of the long distance runner, I have identified practical things that can be done to maintain the function of skeletal muscles and heart. In my next post I will provide a summary of the series, with a list of 12 recommendations for maximising longevity as a runner.