- By observing the transparent cells of roundworms, researchers have uncovered a link between lifespan and the natural cellular process of RNA splicing.
- This research could lead to new breakthroughs in anti-aging treatments that would allow humans to indefinitely keep ourselves healthy, stalling death for as long as possible.
- A new experiment looks into the possibility of replicating stem cell-like conditions through intermittent expressions of genes in order to reverse the signs of aging.
- As a result, human skin cells in a dish looked and behaved young again, and mice with premature aging disease were rejuvenated with a 30% increase in lifespan.
PATTERNS IN SPLICING
Though aging seems like one of the most natural things, an affair common to all living creatures, the process is actually poorly understood by scientists. A new study detailed in Nature aims to shed light on the phenomenon as a research team led by the Harvard T.H. Chan School of Public Health has uncovered a relationship between lifespan and RNA splicing, a core function of cells that allows a single gene to produce a variety of proteins.
The researchers already knew that mutations in RNA splicing could lead to disease, but they wanted to find out if the act of splicing itself had an impact on the aging process. To find out, they designed experimental setups using the roundworm Caenorhabditis elegans, which show visible signs of aging during their short three-week lifespan.
Using fluorescent genetic tools, the team was able to observe the RNA splicing of individual genes in the roundworms’ transparent cells. They noted patterns of splicing that indicated youthfulness or premature aging in the worms and were even able to use these patterns to predict an individual roundworm’s lifespan before any signs of aging became visible. “This…suggests that we might someday be able to use splicing as a kind of biomarker or early signature of aging,” said co-author Caroline Heintz in a press release.
When old age comes, you’ll know it. In addition to telltale signs like greying hair and wrinkled skin though, age comes coupled with an increased risk of age-related diseases. This is why scientists have been studying how aging, which happens on a cellular level, could be halted or even reversed. The latter is the direction researchers at the Salk Institute want to take.
Their research looks into the possibility of replicating stem cell-like conditions through intermittent expressions of genes usually associated with an embryonic state in order to reverse the signs of aging.
“Our study shows that aging may not have to proceed in one single direction,” says senior author Juan Carlos Izpisua Belmonte, Salk Gene Expression Laboratory professor. “It has plasticity and, with careful modulation, aging might be reversed.”
The team’s research is published in the journal Cell.
The researchers prompted cellular rejuvenation through cellular reprogramming that activates the expressions of four genes known as the Yamanaka factors. This process converts cells into induced pluripotent stem cells (iPSCs), — which behave like stem cells, capable of becoming any cell type and can divide indefinitely.
The approach produced promising results: human skin cells in a dish looked and behaved young again, and mice with premature aging disease were rejuvenated with a 30% increase in lifespan.
GETTING IT OUT OF THE LAB
“What we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger,” says 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.”
Of course, iPSCs aren’t necessarily a good thing, especially for adults — after all, non-stop cellular division is a cancer-like behavior and suddenly turning cells young again could result in organ failure.
The team did, however, test the technique on a rare genetic disease called progeria, found in both humans and mice. In the end, they developed a way to induce the Yamanaka factors for a short duration, which was enough to modify the epigenetic marks — which partially drive aging — prematurely dysregulated in progeria.
“[We] now 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,” said author Pradeep Reddy. The process itself needs to be tested before it can go into actual human trials, and the Salk researchers think it would take about 10 years before it could happen.
IS AGING A DISEASE?
When we shift our view of aging from a natural part of life to something modern medicine can possibly prevent, the next step is finding ways to indefinitely keep ourselves healthy, stalling death for as long as possible.
Other researchers are already looking for ways to stop or at least slow down the biological clock. Researchers at the Stanford School of Medicine used chromosome extensions to increase the rate of cell division, a growth mechanism of our bodies that weakens over time. Another breakthrough is Metformin, the so-called “fountain of youth” drug that began clinical tests in February and can supposedly extend animal life and prevent some cancers.
These developments and Mair’s research on RNA splicing are quite far from explaining exactly why our bodies age, and they’re even farther from significantly stalling the biological clock in humans. Until that happens, the search for a way to extend human life will no doubt continue.