Encyclopedia of Bioastronautics

Living Edition
| Editors: Laurence R. Young, Jeffrey P. Sutton

Aging

  • Joan VernikosEmail author
Living reference work entry

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DOI: https://doi.org/10.1007/978-3-319-10152-1_96-2

Definition

Astronauts in space and humans aging on Earth experience similar changes in physiology and function; in space because they live in microgravity whereas on Earth lifestyles make less than optimal use of Earth’s gravity.

Background

When in 1960 Soviet cosmonaut Yuri Gagarin was first launched into space little was known about what to expect. Preceding Soviet animal flights indicated that human survival was probable. Both Soviet and US space programs rapidly progressed to multiple orbits around the Earth, with longer stays on Gemini VII (14 days), Salyut, and eventually Skylab (28, 54, and 84 days). Mir and the International Space Station (ISS) followed. Survival was no longer the issue. A consistent pattern of physiological changes was emerging.

This abnormal physiology that develops in healthy humans in space was soon recognized as having features of accelerated aging (Vernikos 1986; Sandler and Vernikos 1986). But how could that be? What were the mechanisms underlying these changes? (Vernikos 1996). Were they identical to aging? (Vernikos 2004). Would they progress or stabilize with extended stays in space? Would astronauts completely recover postflight? What could be done to prevent or protect space travelers from such adverse consequences? (Nicogossian and Pool 2003).

The advent of shuttle flights provided greater numbers of crew members onboard for durations up to 16 days, with more sophisticated medical diagnostic technology and countermeasure equipment. Nevertheless, progress in research has been slow. The overall number of astronauts that have flown remains small, not to mention the operational difficulties of conducting research in space. No two missions are alike introducing variables such as shift work, social variability as crews rotate, the amount and type of exercise, extravehicular activities (EVA), the several and different experimental protocols they volunteer for – often not the same on any one mission or any single astronaut – all inevitably complicating data interpretation.

A substantial international ground research program therefore evolved over the years using simulation models ranging from water immersion, horizontal (BR) or head-down bed rest (HDBR), and more recently dry immersion bed rest. Studies of days to months in men and women were made possible.

Simulation

What Were These Studies Simulating?

On Earth, gravity (G) is omnipresent. However, it was soon established that using these models induced effects similar to those of living in the reduced G of space. All ground research models relied on ways of reducing the influence of the Gz vector on the body in healthy volunteers. Some like HDBR were more practical for long duration exposures than, for instance, immersion (Pavy Le-Traon et al. 2007).

Fast-forward 55 years when durations in space of 6 months to 1 year are in progress on the ISS with crews of six or seven at a time. The outcome of this research is that so far changes have not stabilized. For instance, bone continues to be lost. Recovery, which was swift and complete after shuttle flights, is slower and often incomplete despite extensive countermeasure approaches as well as more attention paid to rehabilitation.

It should be noted that although animals have been flown in space with no countermeasures, there have been no deliberate noncountermeasure studies in humans in space. All microgravity changes obtained so far develop despite a variety of countermeasures, primarily various forms of exercise, prescribed or self-administered.

What Is Unique About Space?

Reduced gravity (<1G) or microgravity is by far the most interesting variable provided by space flight. The 10−5 gravity level on Earth orbit is below the human sensory threshold required for physiological perception of G. Apollo astronauts on the surface of the Moon; though vertical were unable to anchor themselves on the lunar surface and walk.

This microgravity feature of the space environment provides the opportunity to determine the role of G in our evolution and function here on Earth. HDBR differs from space in that it does not eliminate the Gx vector. In fact, bed rest doubles or increases threefold the number of hours spent per day in the Gx orientation. Though no specific studies have addressed this, there may possibly be consequences on sleep or on a smaller intravascular volume reduction in HDBR (Norsk 2005; Norsk et al. 1998).

Ground simulation in healthy volunteers was essential to provide under controlled conditions the context for interpreting flight observations. Lying continuously in −6° HDBR is now most commonly used as the model of choice. It has made possible studies to determine the time course of physiological changes, the use of provocative investigation of underlying mechanisms, as well as enable the screening of potential countermeasures (Pavy Le-Traon et al. 2007).

Though initially attributed to inactivity (Sandler and Vernikos 1986), other mechanisms are being considered by which space and HDBR induce their effects. One of these is the resultant removal of the alternating exposure to the Gz vector provided by being up and about on Earth.

Similarities to Aging

As early as the Skylab biomedical missions in 1972 some in the medical community commented that reduction in aerobic power, loss of muscle and bone, problems sleeping, as well as balance and coordination issues and orthostatic intolerance on return were reminiscent of symptoms of aging (Weinert and Timiras 2003). A series of 7-day HDBR studies in the early 1980s coincided with my personal involvement in a nearby nursing home. Similarities in young male HDBR subjects during and post–bed rest testing were strikingly similar to those in the home. However, both astronauts and bed rest volunteers recovered on return from space or reambulation from HDBR, respectively, whereas the presumption was and still is that one does not recover from aging.

The conclusion drawn then was that aging and HDBR exposure induced similar, perhaps parallel, but not identical processes (Vernikos 1986). There was no evidence that astronauts died younger. Furthermore, Story Musgrave, John Glenn, and Shannon Lucid, for instance, who flew on Shuttle and Mir missions beyond the age of 50 did not show different responses to microgravity than their younger fellow-astronauts nor did their age interfere with their ability to participate in their operational responsibilities such as EVA and the repair of the Hubble telescope.

The case that spaceflight, bed rest, and aging are the result of identical processes was hard to make since the physiological results follow a different time course and are multifactorial. The responses to spaceflight and bed rest have clean and acute signals of the transition from IGz to either a change in the G vector (Gx) in bed rest or to microgravity, allowing careful and relatively controlled time course studies of the response. Aging, on the other hand, is an ongoing process defined by years in time probably beginning sometime after peak development around age 20. For instance, longitudinal aging studies do not begin at birth or at peak of puberty, but more likely some time in young adulthood (Gross et al. 1998). Therefore, comparing aging persons to astronauts in space is, in fact, like comparing their physiological function through a slice of time, mostly years or decades, during their aging process, to an acute transition to the microgravity state.

Nevertheless, age-like physiological changes in space or HDBR have now been found to be accelerated five- to tenfold compared to similar changes during normal aging on Earth (Lang et al. 2004; Smith et al. 2005; Keyak et al. 2009). Similarly, Ben Levine’s group at Southwestern University College of Medicine showed that similar acceleration of aging occurred in HDBR. The decrease in cardiovascular functional capacity at the end of 3 weeks of HDBR as measured by VO2 max and cardiac output was equivalent to that seen in the same subjects when they were 40 years older. Equally, physiological deficits resulting from a period in microgravity are very similar to those in the elderly such as balance disorders, problems with coordination, muscle weakness, orthostatic hypotension – the drop in blood pressure and tendency to faint on standing up – and a host of atrophic and metabolic disorders. Similarities in the nature and breadth of these changes in otherwise healthy people in all three cases – microgravity, HDBR, or aging – point to a common role of G as the mechanism underlying these changes. Its rate might depend on the low level of G as in space, the reduction of Gz in bed rest, or the reduced use of the Gz vector over decades as a function of age. We are born from the buoyancy of the womb, then develop and evolve in the presence of G. As bipeds, issues such as balance and back pain rely on perfect alignment to the Gz vector.

Lifestyles, like the increasing sedentary behavior of modern times, might be expected to induce similar age-like changes that lie somewhere on the curve between bed rest and aging (Vernikos 2015). In other words, these events suggest a continuum of the rate and degree of age-like changes depending on how much we use the Gz vector. A Gravity Deprivation Syndrome (GDS) was proposed to describe this condition (Vernikos 2011, 2015). Conditions could range from inactive lifestyles in general, too much sitting, lying in bed because of sickness, surgery, injury, chronic disease, or habit or secondary to the limited mobility of aging. They affect all physiological systems, act through common pathways and mechanisms across the board ranging from space to aging. The extreme common result would be characterized by sarcopenia and frailty, which are the well-known consequences of aging. Observations would suggest that the rate of aging on Earth would depend on how inadequately the lifestyle uses the Gz vector. Absolute proof has yet to be obtained, but the data is accumulating. A Gz-rich lifestyle that maintains mobility then would be expected to delay common disorders of poor health with aging.

But Does It Affect Longevity?

There is no direct evidence for or against such a premise. Genetic and epigenetic studies in space and bed rest on an array of established aging genes have yet to be reliably investigated. Though telomere length and telomerase activity, the enzyme that builds and repairs telomeres in each cell, are reduced with aging it would be expected that telomeres will be reduced in space as well. However, the cause would be difficult to pinpoint since conditions other than microgravity, such as radiation, stress, cumulative sleep loss, also cause damage to telomeres. Partial sleep deprivation has been found to activate acutely gene expression patterns in peripheral blood monocytic cells (PBNCs) consistent with increasing accumulation of damage that initiates cell cycle arrest and susceptibility to senescence (Carroll et al. 2015). If acute sleep deprivation, not uncommon in the elderly and space or restriction of sleep experimentally for several days can activate senescence-associated gene expression; similar changes in gene expression could result as a function of microgravity.

What Are These Changes?

The reduced influence of the Gz vector affects physiology in several general ways that are also interrelated and integrated:
  • Changes in hydrostatic pressure resulting in fluid and electrolyte shifts, cardiovascular and lymphatic flow adjustments, and vascular morphology

  • The removal or reduction of proprioceptive and sensory stimulation, input to the vestibular system that senses load, direction, acceleration cues, and generates responses of somatic autonomic peripheral regulatory mechanisms

  • A comprehensive characteristic is atrophic metabolic adaptation, energy balance, central and peripheral detoxification processes

  • Changes in the immuno-lymphatic-gastrointestinal system that may independently respond with shifts in the biome regulatory hierarchy

  • Central regulatory survival adaptations of neural and neuro-endocrine processes involved in breathing, eating, sleeping, stress, and cognition

  • Mechano-transduction from direct push-pull mechanical signals (Ingber 2008; Vernikos and Schneider 2010)

  • Overall sensory sensitivity and integration

This discussion specifically focuses on those aspects that deal with the similarities and differences between space and aging. Table 1 identifies the most obvious such changes revealed by research so far in humans in space, in HDBR, and Aging. Animal studies are referenced as appropriate.
Table 1

Comparison of changes induced by space or HDBR with those of aging

In space and/or HDBR

On Earth with age

↓Plasma volume by 10–20% in 7–180 days

↓Plasma volume by 0.5–1% per decade

↓Aerobic capacity by 10–20% in 4–180 days

↓Aerobic capacity by 10% per decade

↓Heart stroke volume/↓ cardiac output

↓Heart stroke volume/↓cardiac output

↓ Heart muscle mass/cardiomyopathy (unknown)

↓ Heart muscle reserve by 1% a year/scarring

↓ Sensitivity of baroreflex

↓ Sensitivity of baroreflex

Arterial wall stiffness /unknown

Arterial wall stiffness

Blood vessel loss of endothelium lining and NO

Blood vessel loss of endothelium lining and NO

↓ Brain blood flow/↓cerebral oxygenation

↓Brain blood flow/↓cerebral oxygenation/falls

↑Orthostatic hypotension postflight or HDBR

↑ Orthostatic hypotension on standing up

↓Muscle mass by 1% per month in legs/spine

↓Reduced muscle mass by 1% per year

↓ Muscle protein synthesis within hours

↓ Muscle protein synthesis

↓Sensitivity to insulin

↓ Sensitivity to insulin/prediabetic/diabetes

↓Muscle strength proportionately

↓Muscle strength proportionately

Flabby muscles

Flabby muscles

↓Force, explosive power

↓Force, explosive power

Slower movement and reaction time

Slower movement and reaction time

↑ Body fat replaces muscle

↑Body fat replaces muscle

↑Body fat infiltrates liver in HDBR

↑ Body fat infiltrates liver

↓ Lower body bone density by up to 5%/month/loss of Ca/legs, spine/osteopenia

↓ Osteoporosis bone density by 1%/year/loss of Ca/ legs, spine wrists

Risk of bone fracture/ kidney stones

Risk of bone fracture/kidney stones

↓ Collagen/aching joints

↓ Collagen/aching joints

↓Vitamin D3

↓Vitamin D3

↓ Growth hormone and GH response to exercise

↓ Growth hormone and GH response to exercise

↓ Testosterone

↓ Testosterone

Skin loss of endothelium and NO

Skin thinning by loss of endothelium and NO

Study in progress

↓Telomeres and telomerase

Cumulative sleep loss

Cumulative sleep loss

Circadian dysrhythmia

Circadian dysrhythmia

Brain shrinkage/unknown

Brain shrinkage

↓Gastric motility/gut transit time/absorption

↓Gastric motility/gut transit time/absorption

Possible urinary incontinence in women postflight

Urinary incontinence

Tender soles on return or walking

Tender soles on getting out of bed

Poor balance/loss of sense of falling postflight

Poor balance/loss of sense of falling (unknown)

Poor coordination/

Poor coordination/falls

↓height post flight/vertebrae/back pain

↓Height/compressed vertebrae/back pain

Stooped posture and head/head rotation problems

Stooped posture and head/head trunk rotation

Compromised thermoregulation

Compromised thermoregulation

↓ Thirst/hearing?/taste?

↓Thirst/ hearing loss/taste loss

Vision problems

Vision problems

↑Inflammation and oxidative stress

↑Inflammation and oxidative stress

Immunosupression

Immunosupression

Viral reactivation/↑bacterial growth in vitro

Viral reactivation/↑sensitivity to infection

Resistance to antibiotics in vitro

Resistance to antibiotics

↓Wound healing

↓Wound healing

It is readily apparent from Table 1 that there are mostly similarities in the changes induced in space or HDBR or as we age as well as in the mechanisms involved. In few cases, as noted, information is lacking. No doubt, new areas, similar mechanisms, as well as clinical consequences will be revealed over time.

What is strongly evident is that the direction of the changes is overwhelmingly similar. Living in the microgravity of space, lying continuously in bed, and aging induce an atrophic condition. This is not merely visually evident such as loss of muscle or bone but atrophy at all levels – metabolically, morphologically, and functionally. This atrophic condition differs only in the rate at which it is induced.

These changes are generally characterized by the rapid onset of an overall metabolic disorder triggered not only by overall inactivity but also primarily by the absence of the stimulus provided by frequent Gz-related postural change. Loss of fluid and electrolytes leading to reduced plasma volume, red cell mass, and in the endothelium lining affecting the integrity of organs from the skin to blood vessels, bone and other systems that depend on NO generated by sheer forces (Klein-Nulend et al. 2014). NO also activates chromosomal telomerase crucial to delaying senescence. Vascular endothelial cells show damage and reduced nitric oxide (NO) in space (Delp 2007), and it is known that NO has the attribute of activating telomerase in aging endothelial cells in skin (Vasa et al. 2000). NO and the vascular endothelium are crucial in maintaining adequate vascular response to the autonomic nervous system under the control of the vestibular system triggered by a change in posture (Yates et al. 2000) after space, HDBR, or in the clinical setting. Once studied mostly for its role in perception, balance, and coordination, the vestibular system is now being shown to be also involved not only in the maintenance of the cardiovascular system but also of muscle (Luxa et al. 2013) and bone integrity, as well (Vigneaux 2013) as a function of reduced G consequences.

In parallel, rapid reduction in muscle protein synthesis, loss of collagen, and a shift in muscle fiber type from slow to fast is accompanied by reduced anabolic hormone secretions, such as reduced growth hormone and testosterone with insulin resistance, hyperlipidemia, fatty infiltration of the liver and bone marrow, decreased fat oxidation, and a shift in substrate use primarily to glucose. Rapid bone loss, reduced intracellular magnesium, calcium absorption, Vitamin D3, with possible ectopic calcium deposits, and vascular stiffening (Hughson 2016) round off the metabolic scene.

In addition, the syndrome is characterized by inflammation and immunodeficiency. Viral reactivation bacterial growth, and resistance to antibiotics have all been recorded.

Discussion

Providing a framework of similar responses in an integrated manner in space, HDBR, and aging is making possible advances in the understanding of both space and aging physiology.

Once the premise of common mechanisms is recognized, there is much that can be learned from aging research that applies to space. Similarly, much can be learned about aging that studying accelerated age-like changes in space can reveal. Furthermore, using HDBR as a ground model of space to induce premature age-like changes in healthy young volunteers may also serve as a valuable clinical model to study accelerated aging. It could be used, for instance, to tease out the lifestyle- or G-related consequences of aging from genetic, epigenetic, or disease-caused changes. Such research interaction between space, space simulation, and aging would benefit both fields as would advances in experimental approaches and tools.

Equally, knowledge gained from longitudinal studies of aging such as the ongoing Baltimore Longitudinal Study of Aging (BLSA 1958-date) could lead to valuable insight into space physiology and recovery, serving as a framework of what might be anticipated in more prolonged exposure to the microgravity environment of space exploration.

Most significantly, bed rest and spaceflight are extremes of modern sedentary lifestyles. Understanding their health consequences as part of the same syndrome would provide a unified approach to finding solutions for the ills of modern society and premature aging (Vernikos 2015). Not least, bringing the discussion back to G and its crucial role in healthy living may do much to change presumptions of aging, provide novel approaches to public wellness, in support of better health and mobility as we live longer.

References

  1. Baltimore Longitudinal Aging Study, 1958-date. The National Institute of Aging. https://www.blsa.nih.gov/about
  2. Carroll JE, Irwing MR, Stein Merkin S, Seeman TE (2015) Partial sleep deprivation induces DNA damage and senescence in older adults. J Sleep Suppl. June 10. Abstract ID: 0082Google Scholar
  3. Delp MD (2007) Arterial adaptations in microgravity contribute to orthostatic tolerance. Appl J Physiol 102:836CrossRefGoogle Scholar
  4. Hughson RL, Robertson A, Arbeille P, Shoemaker K,Bush JWF, Fraser KS, Greaves DK (2016) Increased postflight carotid artery stiffness and inflight insulin resistance results from 6 mo spaceflight in male and female atronauts. Appl J Physiol 310(5):628–638CrossRefGoogle Scholar
  5. Ingber DE (2008) Tensegrity-based mechanosensing from macro to micro. Prog Biophys Mol Biol 97:163–179CrossRefGoogle Scholar
  6. Keyak JH, Koyama AK, LeBlanc A, Lu Y, Lang TF (2009) Reduction in proximal femoral strength due to long-duration spaceflight. Bone 44:449–453CrossRefGoogle Scholar
  7. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long duration spaceflight. J Bone Miner Res 19:1006–1012CrossRefGoogle Scholar
  8. Luxa N, Salanova M, Schiff G, Gutsmann M, Besnard S, Denise P, Clarke A, Blottner D (2013) Increased myofiber remodeling and NFATc1-myonuclear translocation in rat postural skeletal muscle after experimental vestibular deafferentation. J Vestib Res, 23(4):187–193Google Scholar
  9. McGavock JM, HastingsM, Snell PG, McGuire DK, Pacini EL, Levine BD (2009) A forty-year follow-up of the Dallas bed rest and training study: the effect of age on the cardiovascular response to exercise in men. J Gerontol A Biol Sci Med Sci 64:293–299CrossRefGoogle Scholar
  10. Muller-Delp JM, Spiers SA, Ramsey MW, Delp MD (2002) Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles. Am J Physiol Heart Circ Physiol 283:1662–1672CrossRefGoogle Scholar
  11. Nicogossian AE, Pool SL (2003) Space physiology and medicine, 4th edn. Lippincott Williams & Wilkins, New YorkGoogle Scholar
  12. Norsk P (2005) Cardiovascular and fluid volume control in humans in space. Curr Phar Biotechnol 6(4):325–330CrossRefGoogle Scholar
  13. Norsk P, Christensen NJ, Vorobiev D, Suzuki Y, Drummer C, Heer M (1998) Effects of head down bed rest and microgravity on renal fluid excretion. J Grav Physiol 5(1):81–84Google Scholar
  14. Pavy Le-Traon A, Heer M, Narici MV, Rittweger J, Vernikos J (2007) From space to earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101:143–194CrossRefGoogle Scholar
  15. Sandler H, Vernikos J (eds) (1986) Inactivity: physiological effects. Academic, New York, p 205Google Scholar
  16. Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC (2005) Bone markers, calcium metabolism, and calcium kinetics during extended duration space flight on the Mir space station. J Bone Miner Res 20:208–218CrossRefGoogle Scholar
  17. Vasa M, Breitschopf K, Zeiher AM, Dimmeler S (2000) Nitric oxide activates telomerase and delays endothelial senescence. Circ Res 87:540–542CrossRefGoogle Scholar
  18. Vernikos J (1986) Space and aging: parallel processes. NASA pamphletGoogle Scholar
  19. Vernikos J (1996) Human physiology in space. Bioessays 18:1029–1037CrossRefGoogle Scholar
  20. Vernikos J (2004) The G-connection: harness gravity and reverse aging. iUniverse, Lincoln, p 282Google Scholar
  21. Vernikos J (2011) Sitting kills, moving heals. Quill Books, Fresno, p 132Google Scholar
  22. Vernikos J (2015) Gravity, sitting and health. In: Zhu W, Owen N (eds) Sedentary behavior and health: concepts, assessment & intervention. Human Kinetics, ChampagneGoogle Scholar
  23. Vernikos J, Schneider VS (2010) Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology 56:157–166CrossRefGoogle Scholar
  24. Weinert BT, Timiras PS (2003) Theories of aging. J Appl Physiol 95:1706–1716CrossRefGoogle Scholar
  25. Wilkerson MK, Lesniewski LA, Golding EM, Bryan RM Jr, Amin A, Wison E, Delp MD (2005) Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism. Am J Physiol Heart Circ Physiol 288:1652–1661CrossRefGoogle Scholar
  26. Yates BJ, Holmes MJ, Jian BJ (2000) Adaptive plasticity in vestibular influences on cardiovascular control. Brain Res Bull 53(1):3–9CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Thirdage llcCulpeperUSA

Section editors and affiliations

  • Peter Norsk
    • 1
  1. 1.Division of Space Life SciencesUSRAHoustonUSA