FoxO gene, stem cells, immunity and immortality
German scientists: aging is directly related to the activity of the FoxO gene
LifeSciencesToday based on materials from Kiel University: Solving the mystery of agingWhy are we getting old?
When and from what will we die? Can there be a life without aging? Science has been trying to answer these questions for centuries. Studying why the freshwater polyp hydra is immortal, scientists from the German city of Kiel unexpectedly discovered the connection of this phenomenon with the aging of the human body.
A study conducted by the University of Kiel (Christian-Albrechts-Universitat zu Kiel, CAU) together with the University Clinic of Schleswig-Holstein (Universitatsklinikum Schleswig-Holstein, UKSH), published in the journal Proceedings of the National Academy of Science (Boehm et al., FoxO is a critical regulator of stem cell maintenance in immortal Hydra).
The tiny freshwater hydra shows no signs of aging and is potentially immortal. This apparent paradox – the existence of an immortal living being in a world where all living things are finite – actually has a relatively simple biological explanation: hydra reproduce exclusively by budding, not sexually. The prerequisite for such vegetative reproduction is that the stem cells of any polyp are capable of continuous proliferation. Without such stem cells, this animal will not be able to reproduce. The potential immortality made hydra a particularly interesting object to study the aging process.
In the process of aging, more and more human stem cells lose their ability to reproduce and, consequently, to form new cells. Aging tissue can no longer recover in full, an example of which is age-related muscle atrophy. Elderly people, as a rule, feel weak, because the aging process also affects the muscles of the heart. If these processes could be influenced, good physical well-being would last much longer. Studying animal tissues such as hydra tissues – full of active stem cells throughout life – can provide valuable information about stem cell aging as such.
"Surprisingly, our search for the gene responsible for the immortality of hydra led us to the so–called FoxO gene," says the first author of the study, graduate student Anna-Marei Bohm.
In order to find this gene, scientists isolated hydra stem cells and screened all their genes. The FoxO gene is present in all animals, including humans, and has been known for many years. However, until now it remained unclear why the number of stem cells in humans becomes smaller as they age, and the activity of the remaining ones decreases with age, which biochemical mechanisms are responsible for this gradual extinction and whether the FoxO gene plays any role in aging.
The researchers studied several genetically modified polyps: hydra with normal FoxO activity, with inactive FoxO and with FoxO with increased expression. They were able to show that in animals without FoxO, the number of stem cells is significantly less, and their growth slows down. Interestingly, the immune system also changes in animals with inactive FoxO.
"Gross changes in the immune system, similar to those observed in genetically modified hydra, are also characteristic of older people," explains Philip Rosenstiel from the Institute of Clinical Molecular Biology (Institut für Klinische Molekularbiologie) UKSH, whose research group participated in this work.
"Our group has shown for the first time that there is a direct link between the FoxO gene and aging," comments Professor Thomas Bosch of the Zoological Institute (Zoologischen Institut) CAU, who led the study on hydra. "The high activity of the FoxO gene, already established in centenarians – people over a hundred years old – is, with a high degree of probability, a decisive factor in aging, including in humans."
This hypothesis, of course, cannot be tested directly on the human body, so the next step should be a deeper study of the function of the FoxO longevity gene in hydra and the influence of environmental factors on its activity. But, Professor Bosch emphasizes, the results they obtained are still a big step forward in the study of the human aging process.
The study of German scientists allows us to draw two main scientific conclusions. Firstly, the FoxO gene plays a crucial role in the preservation of stem cells and, thus, determines the life expectancy of animals - from primitive coelenterates to humans. Secondly, the aging and life expectancy of organisms actually depend on two factors: the preservation of stem cells and the maintenance of the functionality of the immune system.
Portal "Eternal youth" http://vechnayamolodost.ru15.11.2012