Aging is characterized by a gradual loss of function at the molecular, cellular, tissue and organism level. At the chromatin level, aging is associated with the gradual accumulation of epigenetic errors, which ultimately leads to abnormal gene regulation, stem cell failure, aging, and cell / tissue dynamic balance disorders. Under normal physiological conditions, the aging process is irreversible. Recently, however, researchers and colleagues at Stanford University have discovered that by inducing senescent cells to temporarily express proteins used to make induced pluripotent cells, older cells can be made younger. This finding may have an impact on aging research.
The processing protein used in the study is Yamanaka factors, which includes Oct3 / 4, Sox2, Klf4 and c-Myc. As we all know, Yamanaka factors are often used to induce the pluripotency of adult somatic cells in biological research. The induced iPS shows both pluripotency and youthful characteristics. Is it possible to simply rewind the aging clock without causing pluripotency? The researchers explored this hypothesis by strictly controlling the duration of exposure of these protein factors. Existing experimental results show that iPS cells can be induced by repeatedly exposing adult cells (such as the cells that make up the skin) to Yamanaka factors for two weeks. Researchers began to wonder whether exposing adult cells to Yamanaka protein for a few days instead of weeks could trigger this young reversal without causing omnipotence. Therefore, the researchers implemented strict control over the duration of protein factor exposure by introducing short-lived RNA information encoding Yamanaka factors into adult cells every day. Over time, these proteins will reverse the fate of the cells-pushing them back along the axis of development time until they resemble the young embryonic pluripotent cells they originated from.
Yamanaka Induces Cell Rejuvenation
Researchers have shown that after being induced to briefly express a set of proteins involved in embryonic development, old human cells will return to a younger and more vibrant state at the molecular level. Since the aging of muscle cells is the most outstanding performance in the aging process of the body, the researchers conducted research experiments on muscle stem cells. Although muscle stem cells have a natural ability to renew themselves, this ability will diminish with age. After protein treatment and repair of the existing muscle stem cells of old mice in vitro, they were transplanted back into the body, and it was found that the appearance of muscle stem cells was obviously rejuvenated. In fact, researchers at the Salk Institute for Biological Research discovered in 2016 that the brief expression of four Yamanaka factors in prematurely aging mice would extend the lifespan of the animals by about 20%. But it is not clear whether this method is applicable to humans. Researchers want to explore whether aging human cells will rejuvenate in a similar way, and whether this method can be extended to many organizations. To this end, the researchers devised a method that uses the instability of messenger RNA to temporarily express 4 kinds of Yamanaka factor and 2 other proteins in human skin and vascular cells. The researchers then compared the gene expression patterns of treated and control cells obtained from the elderly with untreated cells obtained from the young. It was found that cells from the elderly showed signs of reversal of aging only four days after exposure to reprogramming factors. Untreated elderly cells express high levels of genes related to aging, while treated elderly cells are more similar to young cells in gene expression patterns.
Further research found that during protein induction, these cells not only released any memory of their previous identities, but also recovered their youthful state. They completed this transformation by wiping the DNA to remove molecular tags, which not only distinguish the source of the cells but also indicate the age of the cells. The results of the experiment found that the treated cells were younger with untreated elderly cells. Next, they compared several signs of aging between the cells of young people, the untreated cells of the elderly, and the treated cells of the elderly, including how the cells perceive nutrition, metabolize compounds to produce energy, and dispose of cellular waste. Finally, it was found that the aging markers decreased and the cell metabolic capacity increased. Therefore, it is shown that Yamanaka induction can indeed achieve cell rejuvenation to a certain extent.