A group of scientists from the Salk Institute in La Jolla, California, have figured out a way to alter the compass of aging in mice and redirect the hallmarks of growing old – long thought to move in only one direction – into reverse.
Their novel research, which potentially solves a key piece in the aging puzzle, may have vast therapeutic implications if the treatment can be transferred to humans.
“For humans living in modern societies, aging is the largest risk factor for most diseases,” the study authors write in the December 15, 2016, issue of Cell.
The scientists essentially reprogrammed the genetic material in a group of mice affected with the rapid-aging disease known as progeria and extended the life span of the animals by 30 percent.
“Our study shows that aging may not have to proceed in one single direction,” said Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper, in a statement. “It has plasticity and, with careful modulation, aging might be reversed.”
Using Short Blasts to Make Cells Young Again
Using a technique that focuses on the short-term expression of cells’ Yamanaka factors, which are considered critical to the development and aging process, the scientists also counteracted signs of aging in the mice and made old human skin cells – in a lab dish – look young again.
Cardiovascular health and organ functioning also improved in the rodents.
Through previous studies, scientists know that manipulating the Yamanaka factors and teasing other cellular pathways can reprogram cells to appear younger and healthier. But the Salk researchers’ approach provides new insight on the medical community’s ability to create change on a larger basis – and to do so in living beings.
“What we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger,” said Alejandro Ocampo, a research associate and first author of the paper. “The next question was whether we could induce this rejuvenation process in a live animal.”
To test their approach, the scientists had to clear a key hurdle that had vexed researchers – namely, how to avoid damaging healthy cells – because prior studies showed that expressing the Yamanaka factors can lead to the unintended development of cancer.
The research team devised a workaround technique by using “short-term induction” of several genes and thereby avoided the longer-duration approach that had previously proven harmful.
“In other studies scientists have completely reprogrammed cells all the way back to a stem-cell-like state,” said co- author Pradeep Reddy, fellow Salk research associate. “But we show, for the first time, that by expressing these factors for a short duration you can maintain the cell’s identity while reversing age-associated hallmarks.”
The potential ramifications of the Salk researchers’ breakthrough are vast. “Obviously, mice are not humans and we know it will be much more complex to rejuvenate a person,” said Izpisua Belmonte. “But this study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought.”
While the new study warrants excitement, the researchers urge patience – they believe clinical trials may be a decade away.