Stephen Harridge, David Green, Thais Russomano, Ross Pollock & Norman Lazarus
Centre of Human & Aerospace Physiological Sciences, Faculty of Life Sciences & Medicine, King’s College London, UK

https://doi.org/10.36866/pn.98.26

This year sees the first UK member of the European Astronaut Corps, Major Tim Peake, undertake a mission aboard the International Space Station (ISS). The ISS is an international collaborative research laboratory in low earth orbit and Tim is due to stay aboard for 6 months. He follows in the footsteps of Helen Sharman, who became the first Briton in space and British-born American astronaut Mike Foale, who has had extended stays on both the ISS and the Mir station. There will no doubt be a great deal of public interest in Tim’s exploits as he undertakes a wide range of experiments in this unique microgravity (µG) environment.

The costs of launching a manned or unmanned vehicle into space are vast, but so are the economic benefits of possessing a space sector. UK space-related revenues were over £9.1 billion in 2010–11 even without a UK Space Agency (UKSA), only formed in 2010 to assist further growth. The UKSA now contributes on average around £240 million annually to the European Space Agency’s (ESA’s) programmes. Whilst the UK space industry is heavily active in satellite telecommunications and robotics, historically there has been less governmental enthusiasm for human space flight. As a consequence, the UK, despite being a major player in biomedical sciences, has been somewhat side-lined in the space life sciences. However, a big step forward was taken with the formation of the UK Space Biomedical Consortium (recently expanded to become UK Space Labs). This was followed by an unprecedented shift in UK government policy when it signed up not only to ESA’s European Life and Physical Sciences programme (ELIPS) and earth bound µG analogues (e.g. bed rest), but also to ISS utilisation.

Many physiological problems in space

Previously the ISS, Skylab and Mir missions have identified significant multi-faceted physiological de-conditioning in the astronauts and cosmonauts during these prolonged periods in microgravity (µG), leading to the suggestion that long-term space flight might be viewed as model of accelerated human ageing. This is despite the effects of orbital velocity induction of time dilatation, which means that on the ISS, an astronaut will have aged less than those of us will on Earth – albeit by only about 0.005 s with a 6 months stay!

The longest single stay in space by a human is 437 days undertaken by Russian cosmonaut (and physician) Valeri Polyakov. Yet a manned mission to Mars – the long-term goal of NASA – is likely to involve a round trip of at least 500 days. Beyond the Van Allen belt, the µG environment is coupled with increased exposure to solar and galactic cosmic radiation as well as the psychological challenges of isolation, confinement and boredom. Indeed, the challenges of such a mission are orders of magnitude greater than the relatively short duration trips to the moon (~8 days) pioneered by NASA’s Apollo programme in the late 1960s and early 1970s. For NASA, the European Space Agency (ESA) and other space agencies, these challenges require more research into the physiological effects of long-term human space flight and the development of methodologies to counteract them. In this brave new world, the BBSRC also recently committed funding to space-related research as part of its ageing strategy.

So, what are the key physiological effects of prolonged exposure to the µG environment that cause these comparisons between space flight and ageing on earth? The gravitational force of the Earth has shaped our anatomy and physiology for millions of years. When humans are exposed to a prolonged period in space, they are faced with both confinement-enforced inactivity and the continuous gravitational unloading on the body because of the µG environment. Few physiological systems escape unaffected. For example, bones that are no longer required to support body weight lose mass at around 1% per month. This occurs especially in the weight bearing lower limbs, resulting in astronauts developing symptoms similar to osteoporosis (Vico et al., 2000). Skeletal muscles in the limbs and trunk, which are adapted to counteract the effects of gravity, reduce in size, or show signs of atrophy (Narici & de Boer, 2011) – a phenomenon similar in some respects to age-related sarcopenia. In addition, the immune system appears suppressed, often leading to skin infections, and whilst no serious incidents have occurred, some viruses become more virulent. The cardiovascular system adapts to µG by redistribution of body fluids from the lower to the upper body by decreasing plasma volume, red blood cell count (space anaemia) and heart size. Thus an astronaut phenotype develops, characterised by a ‘puffy face’ due to fluid redistribution (cephalic shift), and ‘skinny legs’ due to fluid shift compounded by lower limb muscle atrophy. Unsurprisingly, physical fitness, as determined by the maximal rate of oxygen consumption (VO₂max), also falls markedly due to cardiovascular de-conditioning. At first glance, these changes appear to mimic a number of the physiological characteristics of older people. However, this is a probably a highly simplistic view of the physiology human ageing process.

Whilst in space astronauts undergo numerous countermeasures designed to try to mitigate against the effects of µG. In particular, exercise training regimens now form part of the daily routine for astronauts on the ISS. Specialised exercise equipment designed to allow astronauts to run on treadmills, pedal on cycle ergometers or perform weight, or more appropriately given the µG environment, ‘resistance’ training. A number of platforms for exercise countermeasures thus exist. For example vibrating plates are used to reduce bone loss, which may also help counteract muscle atrophy (Salanova et al., 2014).

However, despite astronauts exercising for at least 2 hours a day, these countermeasures are not completely effective across all systems in counterbalancing the negative effects of µG. This suggests that the two interacting processes of inactivity and unloading require further refined strategies. Furthermore, the challenges faced by astronauts do not end in space.

Problems readapting to normal gravity

On return to Earth, the µG-induced deconditioning persists in 1G and requires appropriate rehabilitation. Orthostatic intolerance is commonplace in the first few days back on Earth, particularly in women, possibly by virtue of greater increments in vascular compliance. However, over time astronauts are able to rehabilitate themselves to pre-flight levels in almost all systems, although bone may be a notable exception. These observations make clear that our physiology is not well equipped for the unloading that results from µG. But then neither is it well equipped to deal with physical inactivity on Earth. Frank Booth put forward the contention that from an evolutionary biological perspective our genes evolved with the expectation of requiring a certain threshold of physical activity (Booth et al., 2002). In this context, exercise must be seen as fundamental to human health; and it is becoming clear that this must extend throughout our lifespan.

Human ageing itself is in some ways, like space, another frontier in which exploration of the effects of inactivity has only just started. As the ageing demographic in Western societies continues to increase, it is becoming increasingly important from economic, health care and quality of life perspectives that this population remains healthy during their increasing working life and throughout the life course. Maximising the ‘health span’ is increasingly replacing longevity or ‘lifespan’ as the prime targets of ageing research.

Crucial importance of exercise in all situations

Unfortunately, too many studies purporting to study the physiology of human ageing have given insufficient attention, or ignored altogether, the influence of physical activity and exercise. In an attempt to define the effects of human ageing free from the confounding effects of inactivity, focus has recently been shifting to older people who undertake high levels of exercise. This population, according to the hypothesis, should maintain an optimum physiology and therefore age optimally because they should be relatively free from the documented complications of inactivity as well as from the negative influences of smoking, poor nutrition and excessive alcohol consumption.

A recent study which undertook a comprehensive physiological analysis of male and female amateur master road cyclists showed that whilst these active individuals have superior level of physiological function compared to their sedentary counterparts (such as in VO2max), the relationship between age and function is not always clear. What is highly likely is that exercise, in all individuals, results in an optimal physiology. Differences between individuals highlight a large genetic component that is likely to influence the profile of physiological function with increasing age. Interestingly, a small scale genetic study will shortly take place in space with NASA astronaut Mark Kelly (aged 51) undertaking a 12 month tour on board the ISS whilst his identical twin brother Scott (former NASA astronaut) remains on earth undergoing the same battery of tests.

Until more is known about the exact exercise regime that is necessary to counter the effects of inactivity and µG on humans in space it is perhaps not yet appropriate to carry the analogy between ageing on Earth and the effects of space too far. Yet there are some areas of clear commonality between spaceflight and ageing, the loss of bone being one. Analogous to the findings in space, not all exercise is equal when applied to bone loss. For example cycling, which has widespread positive effects on many physiological systems, seems to confer no advantage on bone loss when compared with a normal sedentary population. As far as the skeleton seems to be concerned, this type of exercise is analogous to another form of unloading. These types of observations make it clear that exercise is not a panacea and that the type and intensity of exercise both in space and on Earth are important considerations.

If not exercise, then could pills help to counteract the deleterious effects of ageing and space flight? One example is the treatment of a loss in bone mineral density with bisphosphates. A recent study by Lebanc et al., (2013) concluded that the combination of exercise and bisphosphonates provide some protection to bone health for astronauts during long-duration spaceflight. However, pharmaceutical approaches also have innate problems in space. Given the marked effect that the µG environment has on normal physiology, it is more than probable that the pharmacodynamics and pharmacokinetics of drugs will also differ in space.

Indeed, in a recent study it was concluded that 8% of all therapeutic treatments used on board the ISS could be described as ‘ineffective’ (Putcha et al., 2011). Reasons for this include the marked reduction in both gastric and intestinal motility that occur – significantly affecting drug absorption (a phenomenon compounded by space motion sickness), as well as the effects of fluid redistribution. On Earth there are no pharmaceuticals that have the range and effect of exercise in ameliorating the deleterious effects of sedentary ageing. Drugs have been used to counter the effects of the complications of an inactive lifestyle, but these do not address the fundamental problem of preventing these complications in the first place.

Additive effects of ageing and space flight

It is likely that a long-term mission to Mars will involve older astronauts. Thus, in future space exploration, both the effects of inactivity and of the inherent ageing process on physiological processes will need to be addressed. In fact, in 1998 the two issues of human space flight and ageing merged when John Glenn at the age of 77 years became the oldest person to leave the planet and undertake a mission in space. During this 8 day mission he undertook a number of experiments as a Payload Specialist. At the time, there was much debate about whether someone of his age would be able to cope with all of the physiological challenges of the mission. Part of the reason why he was cleared to fly was the remarkable physical condition he was in, having spent many years being highly physically active – in many ways John Glenn epitomises the physiological phenotype that space science must use as a template in order to have successful initial colonising missions. Whilst similarly active individuals must be studied on Earth in order to understand more of the fundamental biology underpinning human ageing. It is thus perhaps appropriate that one of Tim Peake’s outreach activities on the ISS will be the promotion of exercise participation.

References

Booth FW, Chakravarthy MV & Spangenburg EE (2002). Exercise and gene expression: physiological regulation of the human genome through physical activity. J Physiol 543, 399–411.

Leblanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, Smith SM, Evans H, Spector E, Ploutz-Snyder R, Sibonga J, Keyak J, Nakamura T, Kohri K & Ohshima H (2013). Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporos Int 24, 2105–2114.

Narici MV & de Boer MD (2011). Disuse of the musculo-skeletal system in space and on earth. Eur J Appl Physiol 111, 403–420.

Pollock RD, Carter S, Velloso CP, Duggal NA, Lord JM, Lazarus NR & Harridge SDR (2015). An investigation into the relationship between age and physiological function in highly active older adults. J Physiol 593, 657–680.

Putcha L, Taylor PW & Boyd JL (2011). Biopharmaceutical challenges of therapeutics in space: formulation and packaging considerations. Ther Deliv 2, 1373–1376.

Vernikos J & Schneider VS (2010). Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology 56, 157–166.

Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M & Alexandre C (2000). Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet 355, 1607–1611.

Salanova M, Gelfi C, Moriggi M, Vasso M, Viganò A, Minafra L, Bonifacio G, Schiffl G, Gutsmann M, Felsenberg D, Cerretelli P & Blottner D (2014). Disuse deterioration of human skeletal muscle challenged by resistive exercise superimposed with vibration: evidence from structural and proteomic analysis. FASEB J 28, 4748–4763.