Archive for January, 2016

The longevity of the long distance runner, part 3: Cardiac Outcomes

January 10, 2016

After examining the anecdotal evidence provided by elderly marathoners and then grappling with some of the basic science underlying longevity in recent posts, it is time to attempt to draw some practical conclusions about what can be done to optimise longevity as a runner.   While the unfolding science of the molecular mechanisms by which our bodies respond to wear and tear offers intriguing prospects of identifying strategies for promoting heathy aging, there are at this stage more questions than answers. However we each live only once and if we want to optimise our chances of running fluently in old age, we must make the most of the evidence that is currently available. Despite the uncertainties, the evolving science provides a framework for weighing up the value of the lessons that might be drawn from the anecdotes.

But it is necessary to be aware of the pitfalls if we are too simplistic in our interpretation of the science. For example, at first sight the fact that catabolic hormones such as cortisol promote the break-down of body tissues to provide fuel for energy generation in stressful situations, suggests that avoiding sustained elevation of cortisol is likely to promote longevity. Indeed this conclusion might be valid in some circumstances, but it is not a universal rule. The strategy that is most successful for promoting longevity in animals is a calorie restricted diet. This works for creatures as diverse as worms, fish, rodents and dogs, and there is some evidence for health benefits in primates. The mechanisms by which it achieves its benefits include an increase in resistance to oxidative damage to tissues by virtue of more resilient mitochondrial membranes. However calorie restriction is stressful and promotes long term elevation of cortisol. It appears that animals actually need at a least a moderate level of ongoing stress to encourage heathy adaptation. The goal is achieving balance between stressful stimuli and adaptive responses.   The balance point depends on individual circumstances, and is likely to shift as we grow older.

The nature of training

The basic principle of athletic training is stressing the body in order to encourage it to grow stronger. One of the key mechanisms by which this is achieved is inflammation, a process by which damage to tissues generates a cascade of responses mediated by chemical messenger molecules that circulate in the blood stream, triggering repair and strengthening but also leaving a trail of debris.

There is abundant evidence that running increases life expectancy. In a 21 year follow-up study of elderly runners Chakravarty and colleagues at Stanford University found that continuing to run into the seventh and eighth decades has continuing benefits for both life expectancy and reduction of disability. Death rates were less in runners than in controls not only for cardiovascular causes, but also other causes, including cancer, neurological disorders and infections. Nonetheless, unsurprisingly, Chakravarty reported that although the increase in disability with age was substantially less in runners than in non-runners, the runners did nonetheless suffer increasing disability over the follow-up period. This is of course what would be expected if the processes by which training strengthens the body also leave a trail of debris.

If our goal is to increase not only life expectancy but also to achieve healthy aging and longevity as runners, we need to look more closely at the mechanisms by which running damages tissues. Ensuring longevity as a runner requires training in a manner that ensures that the accumulation of debris is minimised.

Healthy aging is a process affecting all parts of the body. Nonetheless, for the runner, the cardiovascular system, musculoskeletal system, nervous systems and endocrine systems are of special importance. There is a large body of evidence about how these systems age and about both the beneficial and the damaging effects of running on these systems.   I will examine the evidence regarding cardiovascular system in this post, and draw some tentative conclusions about how we might train to achieve healthy aging of the heart. In my next post I will examine the evidence regarding the musculo skeletal system, for which much more detailed information about cellular mechanism is available due to the feasibility of tissue biopsy. This will allow us to extend and consolidate the conclusions regarding optimal training for maximizing longevity as a runner.    In the final posts in this series I will turn my attention to the nervous and endocrine systems, and speculate about the way in which optimal training might impact upon health aging of those crucial systems.

Cardiovascular changes

Running produces both short term and long term changes in the cardiovascular system, some beneficial, some potentially harmful. I have discussed many of these changes in several previous blog posts (e.g. ‘The athletes heart’; ‘Inflammation, heart-rhythms, training-effects and overtraining’; ‘Endurance training and heart health, revisited’) and will present a brief overview here.

In the medium term (over time scale of weeks) regular training leads to an increase in blood volume. This increases venous return to the heart. The stretching of the heart muscle leads to more forceful contraction and a greater stroke volume. The cardiac output for a given heart rate is increased. Resting heart rate decreases and the heart rate required to run at a particular sub-maximal pace decreases.

In the longer term, the heart muscle is remodelled, with an increase in overall volume and in thickness of the ventricular walls. This condition is known as ‘athletes heart’. The mechanism is mediated by the intra-cellular signalling pathway that engages an enzyme known as Akt, which promotes growth of both muscle cells and capillaries. This is usually regarded as a benign physiological adaptation. The enlargement of the heart that accompanies pathological conditions such as high blood pressure or obstruction of the heart valves is also mediated by the Akt signalling pathway, but in contrast to the benign enlargement of the athlete’s heart, the Akt signalling is accompanied by inhibition of a growth factor required for the development of capillaries. Thus, in the athlete’s heart the enlargement is accompanied by adequate development of a blood supply to the heart muscle, whereas in pathological conditions the blood supply is usually inadequate.

However, in some athletes the enlargement might have adverse effects. There is compelling evidence that endurance runners with a long history of substantial training have an increased risk of disturbances of heart rhythm, including both ‘supra-ventricular’ disturbances such as atrial fibrillation, and potentially more lethal ventricular disturbances. The cause of these rhythm disturbances is not fully established but it is probable that the re-modelling of the heart muscle in a way that alters electrical conduction pathways plays a role.  It is likely that residual fibrosis at sites where damaged muscle has been repaired also plays a role by producing local irritability of the cardiac muscle cells leading them to fire spontaneously.

During intense prolonged exercise the strength of ventricular contraction, especially that of the right ventricle, is diminished, a condition known as Exercise-Induced Right Ventricular Dysfunction. If the exercise is sufficiently intense and prolonged, cardiac enzymes can be detected in the bloodstream, indicating a least temporary structural damage to heart muscle.

In a study of forty highly trained athletes competing in events ranging from marathon to iron-man triathlon, LaGerche and colleagues from Melbourne found transient weakening of the right ventricle immediately after the event. This was more severe the longer the duration of the event. The transient weakness returned near to normal within a week. However in 5 of the athletes, there was evidence of long term fibrosis of the ventricular septum, indicating chronic damage. Those with evidence suggesting long term damage had an average age of 43 and had been competing for an average of 20 years. Those without evidence of chronic damage had an average age of 35 and had been competing for an average of 8 years.   The evidence suggests that duration of endurance competition is a strong predictor of chronic damage.

Although an enlarged athlete’s heart usually has a much better blood supply than the enlarged heart associated with high blood pressure or obstruction of the heart valves, there is disconcerting but controversial evidence of excessive calcification of the arteries in at least some athletes, especially in males in who run marathons over period of many years. The mechanism is uncertain, though sustained inflammation is a plausible mechanism.

Effects of the amount and type of training

Although an overwhelming mass of evidence demonstrates that runners have a longer life expectancy and in particular, a lower risk of death from heart attack or heart failure than sedentary individuals, several large epidemiological studies raise the possibility that adverse health effects (especially cardiac events) tend to be a little more frequent in those who engage in a large amount of exercise than in those who exercise moderately. The US Aerobic Longitudinal Study examined the associations of running with all-cause and cardiovascular mortality risks in 55,137 adults, aged 18 to 100 years (mean age 44 years) over an average period of 15 years and found a marked decreased in both cardiac and all-cause mortality in runners compared with non-runners, but the reduction in mortality was a little less in those training 6 or more times per week compared with those training 1-5 times per week. The Copenhagen City Heart Study followed 1,098 healthy joggers and 3,950 healthy non-joggers for a period of 12 years and found that 1 to 2.4 hours of jogging per week was associated with the lowest mortality. These ‘moderate’ joggers had a mortality hazard ratio of 0.29 compared with sedentary non-joggers.

But closer look at the evidence reveals a potentially informative detail. In a study of heart health of over a million women, Miranda Armstrong and her co-investigators from Oxford  found that among obese women, those who did a large amount of exercise suffered more heart problems than those who did a moderate amount. However, in contrast, among the women who had a Body Mass Index less than 25, those doing a large amount of exercise had fewer heart problems than those doing a moderate amount of exercise.   This suggests that if there is a risk in doing a large amount of exercise, it is mainly confined to those for whom the exercise is excessively stressful due to other risk factors that shift the balance towards harm rather than benefit.

Although the evidence from the large epidemiological studies remains a topic of debate because of issues such as possible bias in participant selection and the relatively small numbers of individuals in the category who take a very large amount of exercise, I think the balance of evidence does indicate that at least some individuals who take a large amount of exercise do have an increased risk of death, including death form cardiac events, within a given time period.   In my opinion, the important question is what determines which individuals will be harmed by a large amount of exercise, and whether there are ways in which we can minimise the risk of harm.

There is evidence that adequate prior training can protect against damage.   Neilan and colleagues studied non-elite marathoners runners completing the Boston Marathon and reported that right ventricle weakness was more pronounced in those who had trained less than 35 miles per week compared with those who had trained more than 45 miles per week.   The logical conclusion from studies such as the Oxford study of obese female runners and Neilan’s study of marathoners is that running in a manner that exceeds the individual’s current ability to cope with the stress increases the risk of damage.   This in turn suggests that building up gradually in a manner that ensures that training sessions are never excessively stressful is likely to be the safest approach.

Furthermore, it is likely that lack of adequate prior training or obesity are not the only factors that impair the ability to cope with the stress of demanding training and racing. Following a very demanding marathon or ultra-marathon, the evidence of damage remains detectable for a period of weeks. It is plausible that demanding training when the heart is in a weakened state will compound the damage. It is widely accepted in practice that recovery following intense racing or heavy training is crucial, but unfortunately there is relatively little scientific evidence addressing the question of whether or not the adverse cardiac effects of intense exercise resolve during a recovery period, or conversely, whether the adverse effects are compounded by repeated bouts of exercise.   We must therefore turn to evidence from studies of rats.

Benito and colleagues exercised rats on a treadmill for 60 minutes at a quite vigorous pace of 60 cm/s (achieved after 2 weeks of progressive training) 5 days per week for a total of 4 weeks, 8 weeks or 16 weeks. For a rat, 16 weeks of life is roughly equivalent to 10 years for a human. During the first 8 weeks there was relatively little evidence of damage, but prominent signs of damage emerged between 8 and 16 weeks. After the 16 weeks of exercise, the rats exhibited hypertrophy of the left ventricle and also the reduced function of the right ventricle, similar to the findings reported in humans. Furthermore the rats had marked deposits of collagen in the right ventricle, and messenger RNA and protein expression characteristic of fibrosis in both atria and the right ventricle. The exercised rats had an increased susceptibility to induction of ventricular arrhythmias. A sub-group of the rats were examined after an 8 week recovery period following the 16 weeks of exercise. Although the increased weight of the heart had not fully returned to normal level, all of the fibrotic changes that had been observed after 16 weeks of exercise had returned to the normal level observed in sedentary control rats. Thus, at least in rats, the adverse potentially arrhythmigenic changes produced by intense exercise over a 16 week period appear to be reversible after an adequate recovery period.    Thus the best available scientific evidence does support the accepted principle that recovery following intense racing or heavy training is crucial.


Proposed cardiac outcomes of long-term training. The size of the ellipses indicates cardiac fitness at each stage; colour indicates balance between recovery (blue) and stress (red)

In summary, the evidence regarding the cardiovascular effects of running suggests the following guidelines for healthy aging and longevity as a runner:

  • Continuing to run regularly, at least into the seventh and eight decades decreases risk of death and disability.
  • Training volume should be built up gradually.
  • Adequate recovery after demanding events, such as a marathon (or indeed, even after heavy training sessions) is likely to be crucial.

My next post will examine the evidence regarding the effects of training on the musculoskeletal system, and will both consolidate and extend these conclusions.

The longevity of the long distance runner, part 2: the basic science.

January 1, 2016

In my previous blog post I had posed the question: What determines the rate at which a runner’s performance declines with age?   As a prelude to addressing the scientific evidence, I had discussed anecdotal evidence gleaned from the family history, lifestyle and training of the two greatest veteran distance runners of all time: Derek Turnbull and Ed Whitlock. The anecdotal evidence suggested that genes, life-style and training all played a role. Especially in the case of Ed Whitlock, it is probable that having long-lived forebears; deferring very high volume training until after his retirement from work; and adopting a training program designed to minimise stress all contributed to his extraordinary longevity as a world-record breaking marathoner into his mid-eighties.   However, anecdotal evidence provides little basis for drawing general conclusions. What does science tell us?

At first sight, the answer appears to be that science provides a lot of obscure information that in practice offers us little guidance as to how we might adjust our life-style or training to maximise longevity, either as functioning living creatures or more particularly, as athletes. However, if we do not allow ourselves to be put-off by the apparent complexity of the story, it is possible to establish the basis for some simple speculations that might be useful in practice.

Although my primary focus is on longevity as a runner, longevity as a runner is very closely linked to healthy aging.   Healthy aging is not merely freedom from identified illnesses, though many illnesses are common in the elderly and unhealthy elderly people are often afflicted by multiple illnesses.  In fact it is probably more appropriate to consider that healthy aging is a state characterised continued good functioning of all systems of the body, that creates a low vulnerability to illness and is also a requirement for longevity as a runner.

Are there genes for longevity?

There have been several large studies of genes associated with longevity in the general population. These indicate that many genes contribute a small amount to longevity but few contribute an appreciable amount. In fact only one gene has emerged as a significant predictor of longevity in genome-wide association studies: the gene for apolipoprotein E (APOE).   Apolipoprotein E is a protein involved in the transport and metabolism of cholesterol and in several other metabolic functions. The E4 variant of the gene for APOE is associated with substantially increased risk of Alzheimer’s disease and also of heart disease and of increased rate of shortening of telomeres – the protective caps on the ends of chromosome that protect them from damage. Rapid shortening of telomeres is associated with decreased longevity.

We have two copies of each gene (apart from genes on the sex chromosomes), one copy inherited from each parent. In individuals in whom both copies of the APOE gene are the E4 variant, the risk of Alzheimer’s disease is around 15 times greater than in individuals who have two copies of the ‘neutral’ E3 variant, but fortunately very few individuals carry two copies of the E4 variant. However, almost 14% of the population carry one E4 variant. An individual with one copy of E4 together with a copy of E3 has a risk of Alzheimer’s that is about 3 times greater than that of a person with two copies of E3.   Similarly, carrying the unfavourable E4 variant of the gene for APOE does have an apprecibale effect on life expectancy, but even this ‘unfavourable’ gene accounts for only small amount of the variation in longevity in the population. It should also be noted that in contrast, the unfavourable E4 variant is associated with potentially beneficial higher levels of vitamin D which might explain why the gene has persisted in the population despite its unfavourable effects.

But the gene for APOE is the exception. Other genes that appear to contribute to variation in longevity in the population account for a much smaller proportion of the variation than the APOE gene. One other gene that warrants a passing acknowledgement is a gene with the whimsical name, FOXO3. It is a gene that plays a role in regulating gene transcription: the process by which the genetic code specified in our DNA is transcribed onto a temporary RNA copy in preparation for translation into the structure of the proteins that are the building blocks of our bodies. FOXO3 influences the process by which cells die naturally and also plays a role in defence against oxidative damage – a topic we shall return to later.   Its function suggests that FOXO3 is a candidate for an important role in determining longevity, but in fact its influence is not large enough to be discernible above the noise in the data obtained in large (‘genome wide’) studies of the association between genes and longevity.

Genetic variants with small effect

Most of the variants of the many genes that are associated with small alterations in longevity occur commonly in the population. Individually these genetic variants produce a slight perturbation of the structure or function of the body. The very fact that these variants are common demonstrates that individually they cannot have a devastating effect on structure or function, as variants with devastating effects are unlikely to get handed down through many generations.

At this stage it is worth pausing to look briefly at the nature of genetic variation and the mechanism by which it can affect the body’s structure or function. The genetic code is specified by the sequence of the molecular units that a strung together to form the double helical chains of DNA. There are only four of these elementary molecular units, which are assigned the labels A, T, G and C. (These labels are the first letters of the names of the purine and pyrimidine molecules that from part of these units.) DNA consists of a pair of intertwined chains, linked by the bonds that form between A and T or between G and C, at corresponding locations on the two chains Thus each element in the code is either an A-T pair or a G-C pair.  During the preparation for translation, the twinned DNA strands get copied as a single-stranded RNA molecule where each A,T,G, or C unit in one of the DNA chains is copied as a U,A,C or G.   Note that the elementary unit labelled as T (representing the pyrimidine, thymine) in DNA has been replaced by a slightly different molecular unit labelled U (representing the pyrimidine, uracil) in RNA. The crucial thing is that each possible triplet of three sequential units in an RNA chain is the code for a particular amino acid. Amino acids are the basic units that are assembled to form proteins. Proteins are the basic building blocks of the body, serving many specific purposes. Many are enzymes that catalyse the various metabolic processes in the body. Others, such as collagen, are structural elements. The contractile proteins, actin and myosin, enable muscles to do work.

The mechanism by which the genetic code gets transcribed and translated into protein is known as gene expression.  It is gene expression that shapes the structure and function of the body.  As we shall discuss later, many things can influence gene expression.


Figure 1: schematic illustration of gene expression. An extra-cellular signalling molecule (eg an inflammatory cytokine) binds to a specific receptor embedded in the membrane of the cell , triggering a cascade of signalling within the cell. This cascade involves messenger molecules such as cAMP and various effector proteins, including kinase enzymes which activate other proteins by attaching a phosphate group (‘phosphorylation’). When the CREB protein is activated it initiates transcription of DNA, producing an RNA molecule in which the order of the A, U, C & G units is the code for a specific protein. Each triplet of A, U, C & G units represents a particular amino acid. The code specified by the RNA template is translated into the sequence of amino acids that are assembled to make the specified protein. The process of assembling the protein is performed by a molecular construction device called a ribosome.



During the rough and tumble process of cell duplication that occurs regularly in living tissues, one letter of the code might get changed (‘mutated’). This is known as a point mutation, and the resulting variation is known as a Single Nucleotide Polymorphism (SNP). The mutation might be triggered by irradiation by radioactive materials, chemical assault by disruptive chemicals in the environment or the diet, or merely by random jiggling of units making up DNA as it is duplicated during cell division.   As a result of the change in one of the letters, a particular triplet in the code is likely to specify a different amino acid. When the mutant DNA is transcribed into RNA and subsequently translated into a protein, one amino acid will be replaced by another. Just as when a particular footballer is substituted during a football match, the substitution might have a dramatic effect, for better or worse, or alternatively, the team might continue to function with little overall change in effectiveness, in the case of amino acid substitution, there might be either a dramatic change in function of the protein if the substituted amino acid plays a cardinal role or merely a slight change in effectiveness of the protein. Because the sequence of amino acids in proteins has been shaped though many generations, most proteins in the body are well honed to fit their particular role. In the absence of major environmental change, mutations that substantially enhance the fitness of the body for its survival are extremely rare.   On the other hand, mutations that result in serious disruption of the function of the protein diminish fitness for survival, and therefore disappear from the population. The mutations that survive to become common in the population usually have only small effects on the function of the specified protein. In addition to the point mutations that generate SNPs, other types of variation are possible, but these are beyond the scope of this discussion

In summary, the commonly occurring variations in the genes that code for particular proteins usually have only minor effects on the function of those proteins. These functional effects might be helpful or helpful depending on circumstance. But the crucial thing is that it is likely that in most instances various other circumstances including life-style factors might over-ride the relatively minor effect of a specific genetic variant on the structure or function of the body. For most of us, our fate is not pre-ordained by these genes.

One might expect to find that that among the minority of exceptional individuals who live to a great age, the co-existence of many favourable genes each contributing a little, might make an appreciable contribution to their extraordinary longevity. While twin studies demonstrate that the genes contribute only about 25% to the probability of survival to age 85, studies of extremely elderly individuals, such as the study of 801 centenarians (with median age at death of 104 years) by Sebastian and colleagues,, demonstrate that genes play a substantially greater role in the longevity of these exceptional individuals. Similarly, for individuals who exhibit extraordinary longevity as athletes, it is probable that the co-existence of many favourable genes plays an appreciable role. When a large number of small nudges all push in the same direction, their combined effect is appreciable. However for the majority of us, who carry a mixed selection of mildly favourable and unfavourable genetic variants, it is plausible that if we could adopt a range of life-style choices (including appropriate training) that tend to enhance longevity in a consistent manner, we could engineer our fate in a way that swamps the potpourri of random minor influences arising from our genetic endowment.

Gene expression does matter

While the selection of minor genetic variants we happen to have been born with plays only a small part in life-expectancy for most of us, the manner in which our genes are expressed nonetheless plays a crucial role in determining how long we live and how well we continue to function in old age. Unlike an inanimate machine, such as a bicycle with parts that become abraded or degraded by friction and/or corrosion as it grows old, living creatures have inbuilt mechanisms for repair and for correcting internal imbalances that threaten their well-being. A bicycle eventually ceases to function because the abrasion or degradation causes a component to break or jam unless maintained and repaired by an external agency.   However, when a human is subject to wear and tear an elaborate self-repair mechanism is mobilised. The occurrence of damage triggers the release of signalling molecules, which travel via the blood stream to remote regions of the body to mobilise defences. The signalling molecules bind to specific receptors on the surface of the target cell, initiating a series of steps leading to the transcription and translation of DNA to produce proteins that replace or augment the existing proteins as required to repair or even enhance the functions of the body.

After the arrival at the cell surface of a signalling molecule indicating the need for repair or some other response to the external environment, the next step is a cascade of internal signalling within the cell which initiates the transcription of the DNA code onto a temporary RNA template (as discussed above in the review of the process by which the genetic code is expressed, and illustrated in figure 1).

There is a unique RNA template for each protein that is to be constructed. Therefore at any time, the profile of RNA in the cells of a particular tissue indicates which particular proteins are under construction at that time.   The RNA profile of a particular tissue at a particular time is in effect a snap-shot of the multiple building, repair and maintenance processes underway in that tissue at that time.

Environmental factors including life-style and training work in synergy with genes to maintain the body in good working order.   The expression of genes in muscle is not only of particular importance for athletes whose activities are depend on well-functioning muscles, but growing evidence indicates that the expression of genes in muscles is a marker for heathy aging throughout the body. Recent studies indicate that the RNA profile of muscle in late middle age might be a good predictor of the fitness not only of muscle but of other body tissues in subsequent decades.

For example, Sood and colleagues from Kings College, London, demonstrated that a particular RNA profile initially identified in muscle biopsies from a small sample of healthy individuals at age 65, could be used to predict subsequent health of kidneys and brain in several independent samples of elderly people. In one sample followed for 20 years, this profile proved to be a significant predictor of overall survival. Sood proposes that this RNA profile, initially identified in muscle, is a robust marker of healthy aging.

The finding that the state of gene expression in muscle at age 65 can be a good predictor of subsequent overall health is consistent with the observation that self-selected walking speed in late middle age is a strong predictor of survival, and is perhaps of special interest to dedicated runners, though we should not read too much into the fact that the investigators chose to examine muscle tissue. At this stage many question remain unanswered. Two key questions are: what does the set of proteins that are specified by the RNA profile identified by Sood tell us about the molecular processes that characterise healthy aging; and what are the factors that determine the RNA profile in muscle in middle age.

Examination of the list of proteins specified by the identified RNA profile provides few strong clues regarding the molecular processes that characterise healthy aging. Some of the proteins have a known role in cell survival. Perhaps disappointingly for anyone dedicated to running, none of the proteins are those known to be produced in response to vigorous exercise.   However, I am not greatly surprised by this. Although the sample of individual in who the RNA profile was initially identified were healthy and active, none were athletes.   Nonetheless even as a dedicated runner, I find it intriguing that there are features in the current internal state of muscle fibres, other than (or perhaps in addition to) the recognised consequences of vigorous exercise, that indicate current good health and predict future well-being. Vigorous exercise is not all that matters.

Furthermore, the identified RNA profile does not include diminished amounts of the RNA associated with the known risks for diabetes and cardiovascular disease, suggesting that there are aspects s of healthy aging that are not specifically associated with low risk of heart disease. This implies that current guidelines for a healthy lifestyle, which focus largely on known factors associated with cardiovascular health, might fail to include other important aspects of healthy aging.

Perhaps the most important practical issue is whether we can do anything to promote the development of a healthy RNA profile. In general, RNA profile is determined by a combination of genetic and environmental factors.   The fact that genes themselves are not a strong predictor of longevity (except in the small group of exceptional individuals who reach extreme old age) makes it plausible that environmental factors play a large role in promoting the identified healthy RNA profile in middle age. At this stage there is little reason to propose that these factors are uniquely related to muscle. It is possible that influences from elsewhere in the body, such as neural regulation by the brain, the action of hormones or effects produced by other signalling molecules circulating in the blood stream, might shape the RNA profile in muscle.

It is likely that the challenge of remaining a healthy athlete into old age is a ‘whole body’ challenge, and I therefore look forward to future studies that might indicate what can be done to promote the development of a healthy RNA profile in muscle in middle age, irrespective of whether the direct site of action is in muscle or elsewhere in the body.

What can we do now?

Studies such as that of Sood and colleagues provide a fascinating pointer towards future investigations that might enable us to improve our chances of aging in a healthy manner, but it is reasonable to ask what guidance science provides now. In fact there is a substantial body of existing evidence about the mechanisms of cellular repair, protection and maintenance that allows us to make intelligent guesses about what might be helpful.

At the heart of this self-repair mechanism is the process of inflammation. This mechanism is not only responsible for repair of overt damage, but is also the mechanism by which training makes an athlete stronger and fitter. But the mechanism for self-repair does not confer immortality for two reasons. First, inflammation itself can leave a trail of debris in the tissues of the body. The debris is at least partially removed by the crucial scavenging process known as autophagy, but ultimately the residual junk gums up the works. Secondly, it appears that there is a limit to the number of times that the cells of the body can divide to generate new cells to replace those that are worn out. The gradual shortening of the protective telomeres on the ends of chromosomes is a crucial factor in limiting the number of times that cells can divide.

Cardinal among the processes that regulate the maintenance of living tissues are processes mediated by hormones. In particular achieving a balance between catabolic hormones that promote the break-down of tissues, including the process of autophagy, and anabolic hormones that promote the building of tissues, is crucial.

Finally, in light of the fact that gene expression matters throughout life, the cellular mechanism for protecting and repairing DNA itself, are likely to play an important role in life-expectancy and in our longevity as runners.


Figure 2: Schematic illustration of the mechanisms involved in cellular repair. These mechanisms are central to the response to training and also to the responses various other types of cellular damage that are crucial for healthy aging.

Although there is still much to learn about all of these processes, there are things that we can do now that help harness inflammation constructively, achieve a good balance between catabolism and anabolism and perhaps even promote the protection and repair of DNA. But this post has already grown long. I will address these issues in greater detail in future posts