Scientists have made great strides forward in understanding aging after rejuvenating worn out tissues and organs in old mice. MNT spoke to the lead researcher about their work.
Scientists traditionally believed DNA changes caused aging; however, this research suggests epigenetics also play a part. To test this idea further, the team made temporary cuts in mice’s DNA in order to reset their epigenetic patterns and restore health.
How it works
Harvard researchers successfully transformed old mice into young animals by activating a gene that normally prevents cells from becoming too old. Their technique relies on chemical changes called epigenetics which influence gene activity without changing DNA sequence. Studies conducted previously have demonstrated how chemical signals regulate our body’s biological clock and help determine lifespan. DePinho’s team successfully used genetically engineered mice that lack an enzyme called telomerase for this experiment. Without this enzyme, cells’ chromosomes progressively shorten over time until eventually ceasing to function or dying off completely. Our team gave mice injections reactivating their telomerase enzyme to reverse these symptoms of aging in mice including damaged lungs and intestines.
Results
Researchers utilized genome editing technology to induce temporary but quickly healing cuts in mice’s DNA that mimicked environmental and lifestyle factors that can alter how genes function without altering their actual sequences. Reversing these changes reversed their aging process and reversed any premature degenerative symptoms seen.
Scientists were taken aback to find that mice showed a dramatic rebound of normal lifespan after genetic damage that caused them to age was reversed, suggesting it could provide the basis for creating therapies which extend human lives.
One key finding from the Harvard Grant Study was that close relationships are more predictive of longevity than socioeconomic status, IQ or genetics – something DePinho’s group demonstrated through their research that social support can slow aging and enhance quality of life. Medical News Today spoke with Dr. Santosh Kesari of Providence Saint John’s Health Center in Santa Monica about this fascinating research; next steps for him involve discovering how these findings apply to humans.
Conclusions
What began in 1938 as an undergraduate study at Harvard has grown into one of the world’s most remarkable longitudinal research efforts, offering startling lessons about life and death. Over decades, Grant Study participants have experienced personal and professional successes, tragedies, heartbreaks, and everything in between – providing invaluable information about what contributes to a happy, fulfilling, long life.
Researchers used gene editing technology to temporarily create DNA cuts in mice, mimicking what occurs during cell repair following damage to the genome. Their investigation revealed that these cuts activated epigenetic mechanisms – chemical changes to how genes operate without changing their sequence – which were activated as a result.
The team then administered a drug that activated an enzyme known as telomerase to counteract shortening of their telomeres and slow aging biomarkers. As a result, mice appeared and behaved younger while biomarkers suggesting age progression were reversed.
Researchers believe this approach could have wider applications, including reversing certain diseases associated with ageing. MNT spoke with a neurologist from Providence Saint John’s Health Center who was not involved with this particular study and who told them: “This finding sheds light on how genes and environment interact to cause aging; epigenetics is likely an influential factor as well.”
Future plans
The study used mice lacking an enzyme known as telomerase that helps keep chromosomes from shortening prematurely. Without this protective barrier, their bodies began aging prematurely leading to poor sense of smell, infertility, damaged spleens and intestines and premature death. However, when researchers activated telomerase in these mice, their symptoms reversed and they lived longer than before. While repeating this experiment in humans may prove challenging, it should not be impossible. DePinho notes that human cells already contain telomerase, though it is typically kept disabled to prevent cancerous growth. He believes telomerase could be temporarily activated in healthy people to slow or even reverse age-related changes without increasing cancer risks.
Harvard’s Dr David Sinclair recently spoke with American engineer and entrepreneur Peter Diamandis in an interview, where he predicted that pills targeting certain genes will become available within 10 years in order to reverse aging throughout tissues of the body and reverse signs of aging. Furthermore, Sinclair believes scientists may eventually discover ways to nearly double human lifespan.
Sinclair’s work builds on prior research conducted by Shinya Yamanaka, who used a virus to deliver genes capable of activating telomerase in order to rejuvenate aging tissues in mice. Sinclair’s latest research further builds upon these previous efforts using partial cellular reprogramming; this technique allows Yamanaka factor genes to be activated for shorter and more transient periods than full reprogramming would, partially reprogramming cells without fully turning them into stem cells which would lead to creation of new tissues as well as immune responses.
