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The Forefront of Space Science

Space and Aging
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Aging begins soon after birth and aging process accelerates with age. When astronauts adapt to the space environment, functional changes in their bodies including abnormal bone loss and muscle atrophy occur rapidly, comparing with normal aging. These changes resemble the phenomena caused by aging, so it is said that the changes in space represent features of human aging. The difference, however, is that the aging process becomes advanced faster in space than on the ground. It is reported that the muscle weakness in space occurs two times faster comparing with that of a bedridden person, while bones become brittle ten times faster than those of patients with osteoporosis. Furthermore, astronauts are exposed in one day to cosmic radiation of an amount equivalent to up to six months of natural radiation on the ground. Moreover, there are many stress factors in space that are likely to increase the aging phenomenon, including the narrowness of the spaceship cabin and the psychological impact of a long-term stay in the space station.

The author participated the international sample sharing researches of the 13-week mouse-feeding experiment in the international space station (ISS) and of 13-day mouse-feeding experiment in the space shuttle. I have gotten mouse skins with hair, and now I am conducting gene-expression analysis of them. This analysis is useful for study not only on the impact of microgravity or space radiation, but also into the relationship between the space environment and oxidative stress, cell cycle, and the dynamic state of various gene groups related to aging, life-span, and so on. This article discusses the relationship between the space environment and aging/life from the aspect of cellular aging.

What is cellular senescence?

First, what is cellular aging? This describes the process whereby a cell stops repeating general cell division and is unable to multiply and, eventually, this condition continues without returning to its original state. We refer to as the cellular senescence, when a cell to repeat the division stops cell division and is maintained with arrest in cell division. It has been revealed that cellular aging is caused by oxidative stress, radiation, activation of cancer genes, DNA destabilization, damage, and so on. Most cause of cell senescence is in arrest of the cell cycle. It is thought that cellular senescence is a biological defense mechanism to prevent abnormal cell growth, cancer development, inflammation, and so forth. However, cellular senescence is believed to be a factor causing geriatric disease in the long term.

Oxidative stress and radiation stress apply equally to stress in the space environment. What is happen actually in space?

Mouse-feeding experiments in space

In 2009, a 13-week mouse-experiment was conducted using the Mice Drawer System (MDS) developed by Italy in the ISS (Fig. 1A). We used three wild-type (WT) mice and three transgenic (PTN) mice inserted a protein gene to inhibit the differentiation of cells (osteoclast) resorbed bones. Although that was the longest mouse-experiment in space, regrettably two WT mice and one PTN mouse died from probably health problems. The sample sharing research program was carried out for the three healthy mice returned. Our research team took part in the program as one of 20 research groups from six countries and obtained the three mice skins (Fig. 1B). Later we were able to obtain the skins of eight mice, which were stayed for 13 days in NASA’s Animal Enclosure Module (AEM) onboard the last space shuttle mission STS-135 in 2011.

Figure 1
Figure 1. A: NASA astronaut, Nicole Stott, who was working on the Mice Drawer System (MDS) onboard the Japanese Experiment Module Kibo of the International Space Station (ISS). ©NASA
B: Scene of the international sample share. The author (arrowed) can be seen working at NASA’s Kennedy Space Center laboratory.
C: Sample list of expression changes of the gene cluster related to cellular aging

It is suggested that one cause of aging is the accumulation of active oxygen damage with age. It was also reported that an increase in anti-oxidative response helps prolong life and improve the resistance to various environmental stresses, including oxidative stress, and repair ability to DNA damage. Using the DNA microarray and the quantitative real-time polymerase chain reaction (qRT-PCR), we carried out expression-variation analysis on the skins associated with oxidative stress, cell cycles and gene clusters involved in protein synthesis, aging or DNA damage.

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