Skin Ageing - Bone Loss - Muscle Atrophy - Cellular Ageing
Skin AgeingSkin-ageing mechanisms are shown to very much accelerate in microgravity. The time spent in microgravity leads to skin related problems including itching and dryness of the skin, a thinning of the skin and delayed healing of wounds2. Dermal thinning of the skin is observed in astronauts and in mice at International Space Station. The first skin study performed by Tronnier et al, on astronauts as part of SkinCare research supported by European Space Agency (ESA). In the study, noninvasive dermatological test methods are applied before, during and after a long-term mission of astronauts showed coarsening of the epidermis, decreased skin elasticity and thinning of the dermal layer2. A more recent research Skin B again supported by ESA, aims to observe skin physiological changes during long duration space flights on three European astronauts3. For this purpose, measurements on the hydration, the transepidermal water loss, the surface structure, elasticity and the tissue density were performed using a new technology, multiphoton tomography3. As a result, thinning of epidermis and increased collagen level in the upper dermis were found3. Likewise, a more recent long-term research in orbit on skin ageing with mice illustrated a significant reduction of dermal thickness even though there was an increase in procollagen levels4. Additionally, increased amount of collagen was also observed in early human dermal fibroblast cell culture in space5. In this case, reduction in dermal thickness can be explained by early degradation of defective newly formed procollagen molecules as Nusgens and her research team suggests based on their transcriptomic data4. The data, which will be obtained from ongoing Skin B experiment, can enlighten further the skin ageing related mechanisms in space.
Further long term space research with more animals and human participants would enlighten long-term adaptation of human to microgravity conditions and supports development of therapeutic products for decreasing the negative side effects on skin. Since the negative side effects show resemblance of skin ageing on Earth, it would also help development of more efficient anti-ageing products. NASA is also working with cosmetic industries to develop anti ageing skin care products to then be used by astronauts.
Bone LossIn microgravity, adaptation of the skeletal system occurs through the function of bone cells. Bone is mechanosensitive, meaning it adapts to changing environment via mechanical loads. Since in microgravity mechanical load stimulus reduces, the bone loss occurs1. A 4-year study of the long-term effects of microgravity on astronauts showed that they lost 11% of their total hip bone mass in a 4-6 month mission in the International Space Station (ISS)6 which resemble the losses in studies using bed rest. As discussed by the review written by Nagajara & Risin, in spaceflight missions on ISS, seven of eight astronauts revealed decreased bone mineral density around 2.5-10.6% in the lumbar vertebrae7. Moreover, all astronauts experienced around 3-10% bone mineral density loss in the femur and four of them experienced 1.7-10% loss in the femoral neck7. Furthermore, during the spaceflight, bone formation markers such as osteocalcin, bone alkaline phosphatase and the C-terminal peptide of pro-collagen type 1 decreased in astronauts7.
Recovery from the effects induced by microgravity seems to take time and depends on the time spent in space and on the tissue. For example: results obtained from Mir and Space Shuttle showed that after 6 months returning back to Earth, it was observed that trabecular bone mass was not recovered fully, whereas cortical bone was, indicating the presence of a non-complete recovery process7.
Recently, researchers try to find countermeasures for bone loss using stem cells and 3D cell cultures in microgravity or developing novel exercise machines or methods for astronauts. For example: a research performed by Deng et al on mice found that daily short-period of cold temperature showers seems to be an effective treatment for preventing muscle atrophy by strengthening the muscle contraction ability8. Whether the exercise with current fitness equipment at cold temperature will be effective for astronauts should be further discussed.
Muscle AtrophyReduced muscle activity especially the activity of lower limb muscles during spaceflights causes a loss of muscle size and strength and changes muscle physiology1. It is indicated that astronauts in space loose about 1% of muscle and about 1.8-2% of bone per month4. Furthermore, the skeletal muscle changes from type I to type II. Type I fibers are primarily responsible for maintenance of posture and endurance activities, whereas type II fibers are responsible for shorter-duration bursts of speed and power. Fast fibers are more susceptible to fatigue after microgravity based on some studies1.
Microgravity also modifies the cardiac muscle as well, which creates cardiovascular problems. First, since the fluid shift occurs from the lower body to the upper body, it results in upper body blood volume expansion6. This leads to decreased heart size, cardiac output and aerobic capacity. Moreover, lacking of shear forces prevents stimulation of arterial walls, which is thought to end up with constricted arteries6.
However, previous animals studies showed that, if muscle contractions occur at adequate intensity, spaceflight-induced bone formation reductions and mineral loss could be prevented1. Thus, development of new exercise devices with more effective loading capacity on musculoskeletal system, would be very beneficial to prevent bone and muscle loss especially in long-term space missions.
Cellular AgeingThe first ageing experiments were performed with Drosophila melanogaster in space as a part of IML-2 experiment by repeatedly video-recording the activity of fruitflies. As a result, locomotor activity and mitochondrial metabolism increased significantly9. This suggests that microgravity results in a behavioral change, which is reflected in the increased mitochondrial respiration activity that ends up with accelerated ageing9. A more recent research suggested two hypotheses to explain this phenomenon: Firstly, changes in locomotor activity occur to find the gravitational signal. This creates an environmental stress that will lead to an accelerated ageing and a reduction of the survival. Secondly, the altered activity is due to increased energy consumption and causes the acceleration of metabolic rates, which ends up with a reduced survival10.
Further research in this topic would help to understand cellular ageing and mitochondrial metabolism of reactive oxygen species further and to reveal the underlying mechanisms, which might be potential targets for anti-ageing applications.
1. Carpenter, R. D., Lang, T. F., Bloomfield, S. A., Bloomberg, J. J., Judex, S., Keyak, J. H., ... & Spatz, J. M. (2010) Effects of long-duration spaceflight, microgravity, and radiation on the neuromuscular, sensorimotor, and skeletal systems. J. Cosmol, 12,, 3778-3780.
2. Tronnier, H., Wiebusch, M., & Heinrich, U. (2008) Change in skin physiological parameters in space–report on and results of the first study on man. Skin pharmacology and physiology, 21(5), 283-292.
3. König, K., Weinigel, M., Pietruszka, A., Bückle, R., Gerlach, N., & Heinrich, U. (2015) Multiphoton tomography of astronauts. SPIE BiOS (pp. 93290Q-93290Q). International Society for Optics and Photonics.
4. Neutelings, T., Nusgens, B. V., Liu, Y., Tavella, S., Ruggiu, A., Cancedda, R., ... & Lambert, C. (2015) Skin physiology in microgravity: a 3-month stay aboard ISS induces dermal atrophy and affects cutaneous muscle and hair follicles cycling in mice. npj Microgravity, 1, 15002.
5. Seitzer, U., Bodo, M., Müller, P. K., Açil, Y., & Bätge, B. (1995) Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts. Cell and tissue research, 282(3), 513-517.
6. Vernikos, J., & Schneider, V. S. (2009) Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology, 56(2), 157-166.
7. Nagaraja, M. P., & Risin, D. (2013) The current state of bone loss research: data from spaceflight and microgravity simulators. Journal of cellular biochemistry, 114(5), 1001-1008.
8. Deng, C., Wang, P., Zhang, X., & Wang, Y. (2015) Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment. Life sciences in space research, 5, 1-5.
9. Benguría, A., Grande, E., De Juan, E., Ugalde, C., Miquel, J., Garesse, R., & Marco, R. (1996) Microgravity effects on Drosophila melanogaster behavior and aging. Implications of the IML-2 experiment. Journal of biotechnology, 47(2), 191-201.