Senescence reversal in mice achieved through cell reprogramming
Freshening Up the Fountain of Youth
Let's stop mincing words, shall we? Life ain't getting any younger, and scientists are finding ways to turn back the clock.
In the past, we've seen some aspects of cell aging reversed in mice, but it came with a catch—these mice had premature aging, and the experiments ended with some unfortunate consequences, namely, lethal tumors.
But this study published in the journal Nature Aging is a game-changer. The researchers swapped the methods, tweaked the timing, and voilà—they successfully and safely reversed the signs of aging in mice without causing them to grow tumors.
Growing Old (But Not Feeling It)
People have long seen aging as an unavoidable part of life. But it isn't just the passing of years that we should fear—aging increases the risk of serious chronic illnesses like cancer, dementia, type 2 diabetes, and heart disease.
Thankfully, there are things we can do to help reduce the impact of aging, like staying active, eating a healthy diet, getting plenty of sleep, quitting smoking and drinking moderately, and regular check-ups with our doctors.
By 2050, 22% of the United States population will be over 65 years old, so it's essential to find ways to not just add years to our lives but add life to those years.
Retrofitting Cells
Along with lifestyle changes and policy improvements, scientists are exploring new medical interventions that could reduce the physical effects of aging.
The researchers behind this study have discovered that epigenetic markers in mice can be reprogrammed using the molecules Oct4, Sox2, Klf4, and cMyc. These molecules, known as Yamanaka factors, were previously found to increase lifespan and reduce the effects of aging in mice with premature aging without causing cancer.
We chatted with Prof. Juan Carlos Izpisua Belmonte, a researcher at the Gene Expression Laboratory at the Salk Institute for Biological Studies, to shed some light on this breakthrough.
"In our 2016 paper, we developed a protocol that demonstrated, for the first time, that Yamanaka factors could be expressed in mice safely without inducing cancer. We also showed that they could extend the lifespan of premature aging mice by preventing the accumulation of aging phenotypes in cells and tissues," explained Prof. Izpisua Belmonte.
The question remained: would this method work in normal mice over an extended period, and would it be safe?
Aging on Pause
To find out, the researchers divided the mice into three groups: one received Yamanaka factors from 15 to 22 months (around 50 to 70 years in human terms), another from 12 to 22 months (35 to 70 in human years), and the third group was treated for just a single month at 25 months (80 years in human terms).
The results were impressive. Compared to control mice, the mice treated with Yamanaka factors didn't develop cancer, blood cell, or neurological changes. Moreover, mice treated for a number of months displayed various reversals in the effects of aging.
The kidneys and skin of the mice resembled those of younger mice, their skin healed from wounds without excessive scarring, and the scientists didn't observe the usual metabolic changes in the blood typically seen in older animals.
Mice treated for just a single month late in life did not see these effects.
The Road Ahead
Prof. Izpisua Belmonte acknowledges that there are still hurdles before this research can move forward in humans.
"Translating our approach to humans requires developing ways to deliver the factors and controlling the levels and duration they are expressed. These steps will allow us to demonstrate the safe delivery of the factors, a critical aspect before we can even think about clinical trials," said Prof. Izpisua Belmonte.
Still, the findings offer exciting evidence that this technique could have benefits far beyond just the reversal of aging signs.
"After our 2016 study, our lab, as well as several other laboratories around the world, have used the same approach to improve the regeneration of different tissues in mice and rejuvenate human cells," said Prof. Izpisua Belmonte.
If (and when) this research proves successful in humans, we could be looking at a future where aging isn't simply an unavoidable part of life, but something we can address and manage like any other health concern.
Insights:
- FGF21, a hormone, has demonstrated the potential to reverse fatty liver disease in mice, which could contribute to reducing age-related diseases if translated to humans.
- The mTOR pathway, which regulates aging and age-related diseases in animal models, shows that modulating this pathway with drugs like rapamycin could extend lifespan in mice, but further research is necessary for human applications to ensure safety and efficacy.
- Interventions targeting the microbiota, such as those involving specific bacteria like Akkermansia muciniphila, have shown potential in enhancing health outcomes by boosting the immune system, leading to new strategies for healthy aging in humans.
- Advancements in science, like the manipulation of epigenetic markers using Yamanaka factors, could potentially revolutionize health-and-wellness and aging by safely reversing signs of aging and reducing risks associated with medical-conditions such as cancer, dementia, type 2 diabetes, and heart disease.
- As we delve deeper into the realms of science, understanding the roles of hormones like FGF21 in reversing fatty liver disease in mice could pave the way for addressing age-related diseases and offering a promising future for longevity and agingandlongevity.
