To examine whether the space environment may convey anti-aging effects in humans, HRV indices of astronauts on long-term missions were compared between days with relative lower or higher magnetic activity. Tromso’s geomagnetic measures served as surrogate since the ISS is protected by Earth’s magnetosphere. The fact that already during ISS01 SDNNIDX, a surrogate of the VLF-component, is increased on disturbed days suggests an anti-aging effect, as do similar increases during ISS02 in SDNN (a surrogate for the TF-component), SDANN, the Triangular Index and TF-component. The effect of magnetic activity on TF, suggesting an anti-aging effect, was found to be circadian stage-dependent, being more effective during light (12:00–17:00) than during dark (0:00–05:00) (P = 0.0268). The magnetic field in space also induced an activation of the brain’s DMN, gauged by HRV (increase in LF- and MF1-bands). An anti-aging effect in space may thus be mediated by the DMN in a light-dependent manner or/and with help from the circadian clock.

An anti-aging effect of the space environment was reported by Honda et al.18 on Caenorhabditis elegans. While their results indicate that space-flown worms age more slowly compared with ground control worms, the authors note that male Drosophila lived shorter on the ground after spaceflight compared to controls maintained on the ground through their lifetimes18. Caenorhabditis elegans is a classic animal model used to help understand human health concerns due to its short lifespan and ease of culture35,36. Simulated microgravity reportedly could affect early embryogenesis, reproduction and locomotion behavior, and potentially cause the oxidative stress and DNA damage in nematodes37,38,39,40,41.

In the study by Honda et al.18, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel, and insulin-like peptide. One of the genes identified encodes insulin, which is associated with metabolic control. In humans, insulin is also associated with modulation of lifespan. Li et al.42 showed that simulated microgravity could significantly increase the expression of p38 MAPK signaling in the intestine, which may mediate a protection mechanism for animals against the adverse effects from simulated microgravity. Studies in space may provide information about human life that cannot be learned on Earth, including lessons about aging.

The recently published NASA Twins Study describing a multidimensional analysis of a year-long human spaceflight43 also reported that telomeres predominantly lengthened on the ISS, suggesting an anti-aging effect of the space environment. This intriguing change at the chromosomal level, however, could also be interpreted as indicating an increased cancer risk, related to the enhanced exposure to ionizing radiation in space, warranting further investigation of how space weather may affect long-term missions in space.

HRV is defined as the beat-to-beat alterations to the sinus rhythm which result from the interactions between sympathetic and parasympathetic activity32. But HRV is probably more than an indicator of probable disturbances in the autonomous system44. HRV has been considered as a surrogate parameter on complex interactions within biological systems. The relation between reduced HRV and mortality risk was first shown by Wolf et al. in 197845. High HRV is usually associated with good health, whereas low HRV might signify pathological changes, in agreement with the relation between lower HRV parameters and adverse cardiovascular outcomes46,47,48. HRV has recently been considered to reflect the state of the brain as much as the state of the heart49,50,51,52, and is viewed to also reflect the state of health and well-being53,54,55,56, a feature increasingly recognized as a hallmark of anti-aging. Whereas reduced HRV is associated with major risk factors of cognitive impairment, increased HRV indices (including SDNN, SDANN, Triangular Index and TF-, ULF- and VLF-components) are associated with better executive function in the middle aged and elderly57,58,59,60.

The atmosphere gradually ends a hundred kilometers above Earth’s surface. The Earth resides in a vast cavity called the magnetosphere, created by the interaction between Earth’s magnetic field and the solar wind, a gas of charged particles flowing continuously from the Sun. The ISS, which orbits the Earth at an altitude of 330 to 480 km, is also protected from the space environment by Earth’s magnetic field2,26. While conditions in the magnetosphere and on the Sun can potentially influence human health1,2,19, very little is known about their role in the adaptive response of humans to the space environment. The present study is the first to investigate this question.

Time- and frequency-domain HRV endpoints have served as potential markers of stress in organismic functions associated with adaptability and health. For instance, several recent reviews report significantly longer overall survival in cancer patients with higher versus lower HRV55,61,62,63. SDNNIDX and the VLF-component both increased in space in response to magnetic activity after just about one month on the ISS, meaning an activation of HRV in the 0.003–0.04 Hz frequency range. Definite increases in VLF, SDANN, TI, TF, and ULF were later observed on disturbed days during ISS02. SDNN also showed an increasing trend during ISS02. Exposure to variable magnetic fields in space resulted in an increase in several HRV endpoints, suggesting that aging may also be slowed down in astronauts in space, as it was for Caenorhabditis elegans18. The fact that VLF showed a strong response may point to anti-aging effects since VLF power is an indicator of health, lower VLF power being associated with arrhythmic death46 and inflammation64,65.

Why does the VLF-component act most prominently on the autonomous system? Historically, the physiological mechanisms involved in the long-term regulation mechanisms and autonomic nervous activity were linked to thermoregulation, the renin-angiotensin system and other hormonal factors66,67. Studying the autonomic nerves’ re-innervation in the transplanted heart, however, Kember et al.68,69 suggested that the VLF component was generated by the stimulation of afferent sensory neurons in the heart, which in turn activated various levels of the feedback and feed-forward loops in the heart’s intrinsic cardiac nervous system70. The VLF rhythm is now understood to be intrinsically generated by the heart itself, and that the amplitude and frequency of these oscillations are modulated by efferent sympathetic activity. As such, it should be fundamental to health and well-being. An enhanced VLF appearing soon after arrival at the ISS, persisting throughout the space mission may thus represent the most fundamental response to maintain health in space.

During the 5-year experimental span in solar cycle 24, an increased response of HRV was observed in space: 10% in SDNN, 12.5% in SDANN, 8.4% in TI, 17.2% in TF, 31.0% in ULF, 12.7% in VLF, and 9.0% in LF power (Table 2). By contrast, our previous 1998–2000 studies (during solar cycle 23) in a subarctic area indicated that magnetic storms, which involved larger magnetic disturbances than those observed during ISS01 and ISS02, suppressed HRV indices in 19 clinically healthy subjects24. The decrease in HRV was statistically validated for TF (−18.6%, P = 0.00009), primarily contributed to by VLF (−21.9%, P < 0.000001) in conjunction with ULF (−15.5%, P = 0.00865) and LF (−14.2%, P = 0.00187). Solar activity undergoes an about 11-year cycle. HRV decreases associated with geomagnetic storms, which occur more frequently during solar maxima, may increase the cardiovascular disease risk of susceptible individuals. Such an outcome was witnessed in data on mortality from myocardial infarction in Minnesota, which show a 5% increased mortality during years of maximal solar activity (P = 0.023)71. Factors underlying the difference in response observed in space or subarctic areas will need further investigation based on concomitant longitudinal geomagnetic and biomedical monitoring in order to better understand any anti-aging benefits of the space environment, which could then serve to design countermeasures to prevent adverse vascular events on Earth.

Our previous investigation showed a graded response of HRV depending on the degree of geomagnetic activity (gauged by the geomagnetic index ap) in healthy young men living above the arctic circle72,73. Specifically, as compared to days when ap < 7, on days when 7 < ap < 20 or days when 20 < ap < 45, TF was decreased by 18.1% and 31.6%, ULF by 18.1% and 27.5%, and VLF by 12.9% and 28.6%, respectively. A graded decrease of HRV to geomagnetic activity suggests the existence of human magnetoreceptors. Phillips et al.74 proposed a light-dependent magnetoreception mechanism and established a link between magnetic field sensitivity and the visual system in eastern red-spotted newts. A magnetoreception mechanism may thus also exist in humans.

Cryptochromes are blue-light absorbing flavoproteins that in animals have an important function in the circadian clock75,76,77. Furthermore, it has been suggested that cryptochromes act as receptor molecules with magnetically sensitive radical pair reactions in the light-dependent magnetic compass sense of life on Earth78,79,80,81,82. Many animals, including birds, flies, bats, turtles, ants, mole rats, foxes, cows and deer, use the Earth’s magnetic field for orientation and navigation. Nießner et al.83 also localized Cry1 in the retina of Canidae, Mustelidae, Ursidae and some Primates. While humans are not consciously aware of changes in magnetic field and while human magnetoreception has been rarely tested, yielding inconclusive results, a new study84 reports a strong and reproducible human brain response to geomagnetic stimulation, involving a drop in amplitude of EEG alpha oscillations (8–13 Hz) in association with horizontal rotations when the static vertical field is directed downwards. Such alpha event-related desynchronization has previously been linked to sensory and cognitive processing of external stimuli, including vision, auditory and somatosensory cues. Humans are also known to have two cryptochromes (CRY1 and CRY2), which act as clock proteins coordinating the circadian system. Foley et al.85 found that human cryptochrome is sensitive to blue light. Using a transgenic approach, they showed that human CRY2 can act as a magnetic sensor.

Mutant flies lacking the gene for cryptochrome did not respond to magnetic fields, but by transfecting them with two different cryptochrome genes from monarch butterflies they responded to magnetic fields under full-spectrum light78,80. These deletion and replacement experiments showed that the cryptochrome is an essential feature of the light-dependent magnetic sensing system in animals. These animals, however, were exposed to magnetic fields 8 to 10 times stronger than the geomagnetic field on Earth, and similar experiments cannot be conducted in humans, of course.

Our previous investigation showing HRV suppression on days of high geomagnetic disturbance24 found a decrease in HRV only when daylight alternated with darkness (above the arctic circle, there are days of complete light or darkness), suggesting a mechanism sensitive to the alternation of light (L) and darkness (D). The hypothesis of a light-dark-influenced magnetoreception was supported by cross-spectral analysis. Group-averaged coherence at frequencies coincident with the geomagnetic Pc6 pulsations (periods ranging from 10 minutes to 5 hours) differed among the three natural lighting conditions, the association being weaker during L/L or D/D than during D/L (P < 0.000001). A light-dark-influenced magnetoreception mechanism in humans may thus involve the Pc6 band of the magnetic field. Only the magnetoreception in HRV VLF-component was equal throughout the seasons, irrespective of the three natural lighting conditions, suggesting that biological signals involving VLF, which is vital for life, are set-up to be highly sensitive to geomagnetics.

A circadian stage-dependent response of HRV to magnetic activity in space was also found in the present study, the most sensitive response being observed during the daytime (12:00–17:00) and evening (18:00–23:00) (Table 3), when the intensity of illumination on board was around 700 lux. This result is in agreement with the possibility that humans have a light-dependent magnetoreception mechanism that remains functional in space.

Recently we reported that adaptation to microgravity occurs during long-duration spaceflight primarily according to two primary processes, one involving the dynamics of large-scale brain networks, initiated by the default mode network (DMN), and another coordinated by the circadian system11. The adaptation process proceeded even in the absence of consciousness. Herein, we also observed an acceleration of the DMN activity gauged by HRV (Table 2). Our results lead to the hypothesis that exposure to magnetic variation in space, via the retina, or the brain directly, may activate the dynamics of large-scale brain networks, including the DMN. The resulting HRV changes involved an anti-aging effect, enhanced after 6 months in space, together with an adaptation to the novel space environment.

The idea that space-magnetics may directly affect DMN activity, perhaps bringing about an anti-aging effect, is not surprising in view of recent documentation of transcranial magnetic stimulation (TMS) results now being introduced into clinical practice86,87,88. Alterations in DMN activity patterns strongly correlated with depression. In depressed people, disordered activity in the DMN correlates with negative rumination. Liston et al.89 reported that TMS seemed to create a shift in the relationship between two nodes in the DMN, the medial prefrontal cortex and the dorsolateral prefrontal cortex. The medial prefrontal cortex is involved in threat assessment and emotional decision making. The dorsolateral prefrontal cortex, which is where TMS stimulation takes place, seems to be involved in more thoughtful decision making, holding multiple ideas in mind and trying to understand before judging. This shift in functional brain activity could account for the mechanism of action of TMS. It should be noted, however, that magnetic variations in space, of the order of 54000 nT with a SD of 35 to 70 nT, are more than 10,000 times weaker than TMS (1–2 Tesla).

Limitations

This is the first report investigating the effect of magnetic activity on humans’ HRV in space. Whereas it may seem that differences in geomagnetic indices were stronger during ISS01 than during ISS02, these differences may stem mostly from smaller SDs rather than from larger differences per se. Accordingly, it may no longer be surprising that some differences in HRV endpoints are more strongly expressed during ISS02 than during ISS01, a fact that may also be accounted for by the longer adaptation of astronauts to the space environment (see e.g., trajectories of LF/HF, TF, ULF and LF components, and LF-band).

The study was limited by the fact that geomagnetic measures in Tromso, Norway, were used instead of space weather measurements on the ISS. Magnetic activity during ISS01 and ISS02 did not reach levels found during magnetic storms, as it did in our subarctic study. Further studies are needed to assess the relative benefits and risks associated with the full spectrum of space weather conditions on the ISS.

The relatively short ECG records of only 48 hours from only 7 astronauts, monitored twice during a 6-month space mission is another limitation. These records were obtained during a span shorter than the solar activity cycle. Future work is needed to determine whether similar results can be obtained on additional astronauts, preferably based on longer ECG records, so that graded HRV responses to space weather can also be explored. Although larger and longer studies will also be needed to decide whether the physiological changes observed herein actually reflect an anti-aging effect, our results contributed novel information to better understand aging.