Protein discovery could extend human life expectancy by seven years
FARMINGTON — Scientists at the University of Connecticut have made a remarkable breakthrough in the quest for a longer, healthier life. In a large-scale study, researchers were able to extend both the lifespan and healthspan of mice by targeting specific cells in their bodies. This exciting development brings us closer to the dream of not only extending life by years, but also extending the years by lives.
The study was conducted in Cell metabolismfocuses on cells that highly express a protein called p21. These “p21-rich” cells accumulate in various tissues as we age and appear to contribute to age-related performance decline. By periodically eliminating these cells from mice, the scientists were able to extend the animals’ lives by an average of 9%, equivalent to about seven human years. More importantly, the mice remained healthier and more physically fit during their extended lives.
The findings address a key challenge in ageing research: how to increase life expectancy while improving quality of life? Currently, there is often a gap between life expectancy and life expectancy in good health. In some countries, life expectancy is increasing faster than health span, meaning people are living longer but spending more time in poor health.
Targeting p21-rich cells in mice
What makes this study particularly notable is the comprehensive way in which the researchers assessed the health of the mice. Rather than just measuring lifespan or looking at health at a specific point in time, they tracked the mice’s physical function on a monthly basis until their natural death. This allowed them to show that the treatment improved health throughout the remaining lifespan, not just temporarily.
To achieve these remarkable results, the researchers took an innovative approach. They used genetically modified mice that allowed them to specifically target and eliminate the p21-high cells. These mice were equipped with a genetic switch that, when activated, causes the p21-high cells to self-destruct. The scientists began their intervention when the mice were 20 months old, which is about 60-65 human years.
Once a month, the researchers gave the mice a drug called tamoxifen. In the treated mice, this drug activated the genetic switch, causing the p21-high cells to die. Control mice received the same drug but lacked the genetic switch, so their p21-high cells remained intact.
Fountain of youth effect
The treated mice showed better grip strength, faster walking speeds, and lower frailty scores compared to untreated mice. They also had improved heart function, better glucose tolerance and insulin sensitivity, and healthier livers. All of these benefits persisted even into the last months of life, suggesting a true extension of health span.
Interestingly, the treatment did not appear to prevent any specific diseases. Instead, it seemed to slow the overall aging process, leading to better health across multiple body systems. This is consistent with the idea that targeting underlying aging processes may be more effective than trying to treat individual age-related diseases one at a time.
But the benefits didn’t stop there. The treated mice also showed improvements in several important health areas:
- Better heart function: Echocardiograms showed that the treated mice had a stronger and more efficient heart.
- Improved metabolism: The mice showed better glucose tolerance and insulin sensitivity, indicating a healthier metabolism and a potentially lower risk of diabetes.
- Healthier liver: Blood tests showed lower levels of enzymes associated with liver damage in the treated mice.
Importantly, these health benefits even lasted into the last months of life, suggesting a real extension of healthspan – the period of life spent in good health.
The researchers believe their approach works by reducing chronic, low-grade inflammation that accompanies aging. The p21-rich cells appear to produce inflammatory signals that can spread throughout the body and increase inflammation. By regularly eliminating these cells, the treatment could reduce this harmful inflammation.
Improving people’s health and life expectancy
If similar results could be achieved in humans, it could lead to a significant improvement in the quality of life of older people. Imagine being able to remain physically active, mentally fit and independent for years longer than is currently possible. The economic and social impact would be huge, potentially reducing healthcare costs and allowing people to contribute to society for longer.
“We are all very excited about this discovery because it shows that we are not just extending lifespan, but actually extending life in good health in mice, which is an important goal in aging research,” said Ming Xu, assistant professor in the UConn Center on Aging and the Department of Genetics and Genome Sciences at UConn, in a statement.
Of course, we are still a long way from achieving this in humans. But this study takes anti-aging research in an exciting new direction and offers hope that we may one day be able to extend not only our lifespan, but our healthspan as well.
Summary of the paper
methodology
The researchers used genetically modified mice that allowed them to specifically target and eliminate p21-high cells. Starting at 20 months of age (equivalent to about 60-65 human years), they gave the mice a drug called tamoxifen once a month. In the treated mice, this drug activated a genetic switch that caused p21-high cells to self-destruct. They then monitored the mice’s health and physical function monthly until they died of natural causes, and compared the treated mice with untreated control mice.
Results
The treated mice lived an average of about 9% longer, some as much as 8% longer, than the longest-living control mice. Over the course of their lives, they performed better on tests of grip strength and walking speed. They also scored lower on a “frailty index” that measures various signs of aging. In addition, the treated mice showed better heart function, improved glucose metabolism and healthier livers compared to untreated mice.
restrictions
This study was conducted in mice, and results in animals do not always translate to humans. The genetic changes used in this study to target p21-rich cells are not possible in humans, so other methods would need to be developed for potential human treatments. The study also did not examine the potential negative effects of eliminating these cells, which could be important for long-term safety.
Discussion and findings
The researchers believe their approach works by reducing chronic, low-grade inflammation that accompanies aging. The p21-rich cells appear to produce inflammatory signals that can spread throughout the body and increase inflammation. By regularly eliminating these cells, the treatment could reduce this harmful inflammation.
The study suggests that targeting underlying aging processes could promote healthier aging than attempting to treat individual age-related diseases. It also underscores the importance of considering not only lifespan but also healthspan in aging research.
The researchers point out that their approach appears to work differently than other anti-aging strategies that target other types of aged cells, suggesting that there may be multiple types of problematic cells that contribute to aging in different ways.
Financing and Disclosures
The study was funded by several organizations, including the Glenn Foundation for Medical Research, the National Institutes of Health, and others. Some of the researchers have filed a patent for the mouse model used in the study, which could potentially create financial conflicts of interest if the technology is commercialized in the future.
