This age of biotechnology is also an age of comparative indolence and comfort. As the research community measures specific biochemical aspects of aging, such as the decline of the cardiovascular system, or metrics relating to immunosenescence in the immune system, we might question the degree to which the results are peculiar to our era. How much of aging is the result of our choices - to eat more and exercise less than our ancestors - rather than the result of inexorable processes of biochemical damage that we, as yet, have little influence over? (Conversely, how much of past aging was due to infectious disease, malnutrition, and other adverse external circumstances that are controlled to a much greater degree today?) This topic crops up fairly often in research into the effects of exercise on health, and the research noted here is a particularly striking example of the type.
The study authors find that the age-related decline of new T cells maturing in the thymus is negligible in some people, those who exercise much more than the rest of us. This diminished supply of new T cells is thought to be an important component of immune system aging, and the failure of the immune system is very influential over many other aspects of aging: senescent cell accumulation, frailty, loss of regenerative capacity, chronic inflammation, cancer risk, and so on. Yet when we look at the demographic evidence for spread of life span based on exercise, it appears to be, at most, 6 or 7 years (with a much larger divergence when it comes to state of health over time). What does this tell us about the likely gains resulting from rejuvenation therapies seeking to regenerate the thymus? Less than we would like, I suspect, and not just because it is hard to evaluate any one contribution to aging in isolation of all of the others.
The thymus atrophies over adult life, with active tissue necessary for the production of T cells being replaced by fat. The first major loss of active thymic tissue occurs at the end of childhood, however, in a process known as involution. Immune cells are generated at a tremendous rate in children in comparison to young adults; evolution selected for a system that would be highly effective at the outset, at the cost of later issues. When it is observed that old people in their 60s and 70s who maintained a high level of fitness throughout life exhibit much the same thymic output as young people in their 20s, that tells us little regarding the outcome were the thymus restored to the same level of active tissue as is present in children. Only a mild restoration, to move thymic activity from typical aged to typical young adult, would be comparable - and why would we stop there?
Prehistoric hunter-gatherer tribes were highly active, spending a lot of time and energy sourcing their food. If they weren't successful, they would also spend days with or little or no food. By contrast, today we are a highly sedentary society. As we get older, our physical activity levels decline even further. In our research, we have tried to determine how much this low level of physical activity contributes to the ageing of many body systems, including muscle, bone and the immune system.
We examined 125 male and female cyclists, aged 55 to 79, who had maintained a high level of cycling throughout most of their adult lives. These were not Olympians, but very keen cyclists who were able to cycle 100km in under 6.5 hours for the men, and 60km in under 5.5 hours for the women. At mid-life, people start losing muscle mass and strength at a rate of 1% to 2% per year, making it harder to carry out their normal activities such as climbing stairs. Our bones also become thinner with age and this can eventually lead to diseases such as osteoporosis. We showed that the cyclists did not lose muscle mass or strength as they aged, and their bones only became slightly thinner. We then went on to examine a body system that was not so obviously influenced by physical activity - the immune system.
When we compared the immune system of the cyclists to older adults who had not done regular exercise, and to young people in their twenties, we found that their immune systems looked most like the young persons'. In particular, we found that the cyclists still made lots of new immune T cells, produced by an organ called the thymus, which normally starts to shrink after we reach puberty. The older cyclists seemed to have a thymus that was making as many new T cells as the young people's. We investigated why this happened and found that the cyclists had high levels of a hormone called interleukin 7 in their blood, which helps to stop the thymus shrinking. Interleukin 7 is made by many cells in the body, including muscle cells, so we think that active muscles will make more of this hormone and keep the immune system, and especially the thymus, young.
What confounds human studies of immunosenescence is that physical activity is not taken into account in either cross-sectional or longitudinal studies of immune aging. The majority of older adults are largely sedentary and fail to meet the recommended guidelines for physical activity of 150 min of aerobic exercise per week. Regular physical activity in older adults has been associated with lower levels of pro-inflammatory cytokines such as IL-6, TNFα, improved neutrophil chemotaxis and NK cell cytotoxicity, increased T-cell proliferation and improved vaccination responses. Thus, the current literature on immunesenescence is not able to determine which aspects of age-related immune change are driven by extrinsic factors and which may be the consequence of a constitutive aging programme.
Here, we studied several aspects of the adaptive immune system in highly physically active older individuals (master cyclists) in which we have shown the maintenance of a range of physiological functions previously reported to decline with age. We show that compared with more sedentary older adults, the cyclists show reduced evidence of a decline in thymic output, inflammaging and increased Th17 cell responses, although accumulation of senescent T cells still occurred. We reveal high serum levels of IL-7 and IL-15 and low IL-6, which would together provide a environment protective of the thymus and also help to maintain naïve T cells in the periphery. We conclude that maintained physical activity into middle and old age protects against many aspects of immune aging which are in large part lifestyle driven.