Lab mice have had their biological age successfully reversed. David Sinclair, a professor of genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, has spent much of his career studying the biological process of aging. His most recent research has found a way to not only speed up the process of aging at will, but to reverse it, as well.
Previously, the general belief was that aging is caused by changes to DNA over time. Now, Sinclair and his team believe changing DNA may only be a small piece of the puzzle. Their research supports the idea that epigenetic change is the main cause of what prompts our bodies to age. Epigenetics – the way DNA is organized and regulated – are to DNA what an operating system is to a computer. Although the DNA contains the necessary hardware, epigenomes tell the DNA what to do and when and where to do it. Factors such as diet, exercise, environment, and overall lifestyle affect epigenetics, and changes to epigenetics appear to be reversible. For example, although epigenetic dysregulation can lead to diseases such as cancer, it is possible to return to a previous epigenetic state. A study on smokers, non-smokers, and former smokers observed such an occurrence.
Epigenetic factors oversee the regulation of gene expression and the structure of tightly compacted DNA known as chromatin. As DNA becomes damaged, these factors put their regulation duties on pause to travel to the location of the damage and repair it, and then they return to their original position. However, after many successive repairs, these factors begin to malfunction. They will begin “turning off” genes that should be on, “turning on” genes that should be off, and they even lose their way back to their original locations. Sinclair’s recent findings suggest that this epigenetic malfunctioning is the process which drives aging. His lab’s findings also suggest that even after these factors begin malfunctioning, they can be reset.
To test his theories, Sinclair and his team have been inducing fast-healing DNA cuts in mice. These small cuts are meant to simulate typical environmental damage without triggering mutations. After many DNA repairs, the epigenome becomes disorganized and speeds up the aging process. Tissues of the mice’s brains, eyes, muscles, skin, and kidneys were consistent with mice twice their age.
Next, Sinclair wanted to test the theory that these changes were reversible. In 2020, Sinclair’s lab used a gene therapy to reverse age-related vision loss similar to glaucoma in humans. The therapy successfully restored vision in mice by recapturing youthful gene function. In Sinclair’s most recent research, the same gene therapy was introduced to mice that had their aging processes sped up. As expected, the organs and tissues of these mice returned to a youthful state. The cells reportedly reversed back to 50 or 75 percent of their current biological age. Sinclair describes the process as a permanent restoration of the epigenetic information that the mice had when they were young. Further, multiple treatments will prompt the reset as many times.
Sinclair discusses the implications of their successful control over the biological age of a complex animal, including the possibility of being able to “treat multiple, seemingly unrelated diseases with a single medicine”. He suggests that age-related diseases and conditions such as cardiovascular disease, neurodegeneration, and frailty may one day be things of the past. Until then, his research continues as studies to replicate these results in primates are currently underway.