28 May 2012

To combat the aging of stem cells, it is necessary to rejuvenate their niche

Scientists have managed to reverse the aging of stem cells

LifeSciencesToday by Salk Institute for Biological Studies: Researchers find a way to delay aging of stem cellsStem cells are irreplaceable building blocks of any organism – from plants to humans.

They divide and renew throughout life, differentiating into cells of specialized tissues necessary during development, as well as into cells that restore the tissues of an adult organism. The ability of stem cells to recreate themselves and regenerate tissues throughout the life of an organism allows them to be considered immortal. However, this does not mean that they do not age. They age and gradually lose the ability to effectively support tissues and organs.

Scientists from the Salk Institute for Biological Studies have just described a number of biological events concerning the state of the stem cell microenvironment, known as the "stem cell niche", as the cause of the loss of active stem cells in the aging process. Their discovery, published in the journal Nature (The let-7–Imp axis regulates aging of the Drosophila testis stem-cell niche), is directly related to the treatment of age-related diseases and the effectiveness of regenerative medicine.

"The data obtained suggest that, for example, the introduction of new or young stem cells into an old microenvironment – the microenvironment of an old patient – may not lead to the desired result in tissue regeneration," comments the results of the study, its head Lynn Jones (Leanne Jones), PhD, associate professor of the laboratory of genetics at the Salk Institute.

Stem cells are located in a microenvironment consisting of other cells – a niche of stem cells – which, as is known, plays an important role in their functioning. For example, after tissue damage, the stem cell niche signals the need to create a new tissue. It is believed that stem cells exchange signals with their niches, which helps them to remain active throughout life.

Today, scientists explain the loss of functions of tissues and organs in the aging process by weakening the function of stem cells. But exactly how their activity declines remains unclear. Dr. Jones' laboratory investigated several possible scenarios for the development of events. The scientists wanted to find out what explains the loss of tissue function – a decrease in the number of stem cells, the inability of stem cells to respond to signals from their niche, or the weakening of the niche signaling itself.

To study the aging of stem cells, Dr. Jones chose the cells of the sex glands of male fruit flies Drosophila melanogaster, surprisingly similar to human ones.

The scientists concluded that the signals from the stem cell niche that support cell viability are lost over time, which leads to a decrease in the number of stem cells that can effectively maintain the normal state of the tissue. However, the restoration of these signals revitalizes the cells.

"The stem cells of flies and humans behave the same, so the data we have obtained can lead to major advances in the use of tissue stem cells for the treatment of age–related extinction of tissue functions or regeneration after injury," comments the possible use of the results of her first author Hila Toledano (Hila Toledano), PhD.

Scientists have found that with aging, niche cells produce microRNA (a molecule that plays a negative role in protein synthesis) let-7. This microRNA is known to exist in a number of biological species, including humans, and helps to determine the sequence of events in the process of development of the organism.

The increased synthesis of let-7 microRNA leads to a domino effect that switches the aging switch, affecting the Imp protein, whose function is to protect another molecule, Upd, secreted by a key area of the stem cell niche.

Fluorescent images of the testes of young (left) and old male fruit flies show the effect of aging on the stem cell niche (top center). In old flies, the cells (red) functioning as part of the stem cell-supporting niche express more let-7 microRNA (green), which changes their signaling properties, leading to a decrease in the number of stem cells capable of maintaining the normal state of the tissue.

In short, Upd stimulates signaling that supports the activity of stem cells and their contact with the niche, as a result of which they retain the ability to self-renew. But as we age, the increased expression of let-7 microRNA eventually leads to a decrease in Upd levels, reducing the number of active stem cells. The question of what leads to the accumulation of let-7 microRNAs in the niche in old flies remains open.

Scientists have managed to reverse the age-related loss of stem cells by increasing the expression of Imp.

"We have turned off aging," says Dr. Jones.

There are several ways to counteract aging: by preventing an increase in let-7 microRNA expression, blocking Upd destruction, or enhancing Imp expression.

"This study opens up new perspectives in the development of drugs focused on stimulating the ability to overcome the effects of aging of the patient's own stem cells," explains Dr. Toledano.

Scientists have uncovered the mechanism of stem cell niche loss of its supporting function and demonstrated that the molecular events involved in it can be reversed. According to Dr. Jones, in relation to patients, in order to support the stem cells transplanted by them, this may mean co-transplantation of the components of the niche itself or rejuvenation of the niche through drug therapy.

Portal "Eternal youth" http://vechnayamolodost.ru28.05.2012

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