Stem cells are the body’s raw materials — cells that can turn into any other type of cell in the body, from muscle cells to brain cells. Pluripotent stem cells can undergo self-renewal and are vital for the healthy development of embryos. They have been the subject of numerous studies in recent years with induced pluripotent stem cells (iPS cells), becoming an emerging method for repairing damage to organs and tissues.
Such treatments involve scientists collecting samples of a patient’s adult cells and then exposing them to proteins known as Yamanaka factors. These proteins can revert cells to an embryonic state – to the point when they can again become whatever specialized cells are needed. These iPS cells are the magic ingredient in regenerative medicine and new drug discoveries.
Aside from using iPS cells to heal and cure people, some researchers have been looking into using them to rewind aging. During the transition (from an adult cell back to a pluripotent stem cell), the cells shed memories of previous identities, until there are no memories left. The DNA is wiped clean of molecular tags that differentiate it (for example, a heart cell from a skin cell) and other tags that accumulate as the cell ages.
Therefore, by inducing old cells to express these Yamanaka factors briefly, it rewinds many of the molecular hallmarks of aging. A new study by researchers at the Stanford University School of Medicine found this to be exact – that the old cells (in a lab dish) were nearly indistinguishable from their younger counterparts. The team also found that (in animal tests) older mice regained the muscle strength of youth when their existing muscle stem cells were treated and transplanted back into their bodies.
Vittorio Sebastiano, the senior author of the study, said:
When iPS cells are made from adult cells, they become both youthful and pluripotent. We’ve wondered for some time if it might be possible to simply rewind the aging clock without inducing pluripotency. Now we’ve found that, by tightly controlling the duration of the exposure to these protein factors, we can promote rejuvenation in multiple human cell types.
The main difference in this Stanford study and the usual method of turning adult cells into iPS cells is the duration of exposure to the rejuvenating proteins. To create iPS cells involves several weeks of exposure to Yamanaka factors to get them to reach the embryonic stage. However, the researchers only wanted the cells to become younger, so they tested what a few days might do instead. In other words, rather than rewind the age to newborn, they stopped it in the twenties.
When they stopped the process four days in, elderly human cells resembled younger cells. They know this from analyzing the patterns of methyl groups – aging-associated chemical tags that serve as a gauge of a cell’s chronological age. Treated elderly skin cells appeared 1½ to 3½ years younger than untreated elderly cells, while blood vessel cells appeared up to 7½ years younger.
When they compared other hallmarks of aging – such as how cells metabolize compounds to create energy, sense nutrients, and dispose of cellular trash – they found dramatic rejuvenation. They even tested cartilage cells from people with osteoarthritis and found the treatment lowered inflammation and improved the cells’ functionality and ability to divide.
Sebastiano said:
We saw a dramatic rejuvenation across all hallmarks but one in all the cell types tested. But our last and most important experiment was done on muscle stem cells. Although they are naturally endowed with the ability to self-renew, this capacity wanes with age. We wondered, can we also rejuvenate stem cells and have a long-term effect?
The mouse tests were perhaps most impressive! Elderly mice who had treated muscle cells transplanted into their bodies regained the muscle strength of younger mice.
Sebastiano said:
Although much more work needs to be done, we are hopeful that we may one day have the opportunity to reboot entire tissues. But first we want to make sure that this is rigorously tested in the lab and found to be safe.
Now, the team is optimizing the group of reprogramming proteins used in the treatment and seeing if it’s possible to treat cells without having to remove them from the body, thus eliminating the need for transplantation.
A couple of other recent anti-aging treatments include one that targets and eliminates old cells, which passed its first human trial and another that reverses the aging process by lengthening a person’s telomeres.
