May 3, 2024

I, Science

The science magazine of Imperial College

by Julie Hoeflinger (2 February 2023)

Researchers have been trying to figure out the causes of aging for decades, and they may have finally figured out how to slow the process down. In a groundbreaking decade-long, international study published in Cell earlier this month, researchers discovered a driving factor of what causes us to age and were able to manipulate it in order to reverse certain hallmarks of the aging process in mice. 

Originally, scientists thought that direct changes to our DNA were the main, and perhaps only, factor causing us to age. Some researchers in the field believed that we age primarily due to gradual degradation of our genetic code, largely due to the accumulation of mutations in the DNA, and that this is what leads to malfunctioning tissues and organs as we grow older. 

But the team who conducted this study found that there was something else that could accelerate – and even reverse – signs of aging.  

This other variable is known as epigenetics. Epigenetics is concerned with the way genetic material is expressed rather than with the molecular makeup of the genetic material itself. It determines which genes (which are like instruction manuals for your body) are activated or silenced.  

As we age, we lose genetic and epigenetic information. This study found, for the very first time, that restoring the loss of epigenetic information can reverse certain biological hallmarks of aging, such as poor vision. And epigenetic changes are much easier to manipulate than direct changes to the DNA, thus overcoming one of the major previous challenges to this field of research.   

The team accomplished this by first artificially inducing aging in mice. In the natural world, numerous inevitable factors cause damage to our DNA, such as air pollution, and that seems to cause us to age. So, the researchers replicated this damage by applying cuts to the mice’s DNA. In just a few weeks’ time, the mice showed advanced signs of aging: their fur turned grey, they become frailer and less active, and so on.  

The mice then received a gene therapy with a few genes involved in cell identity. In other words, the aged cells received instructions from these genes for a sort of “system reboot” that causes the cells to reprogram themselves to a more youthful state. 

“We hope these results are seen as a turning point in our ability to control aging,” the study’s senior author Dr. David Sinclair, professor of genetics at Harvard Medical School, said in a Harvard Medical School news report. “This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will.” 

Does this mean we’ll be able to revert back to younger versions of ourselves one day? Not quite. More feasibly, we may be able to slow certain aspects of the aging process, like the age and health of various organs and cells, which could be particularly useful in slowing the progression of age-related diseases including Alzheimer’s disease. However, it’s important to keep in mind that there are many factors driving aging, and epigenetic changes are just one of them. 

The next step is to replicate these results in larger mammals and humans, and studies in non-human primates are already underway. Of course, there are a lot of ethical gray areas surrounding this research, and we’re still quite a long way from any applicable treatments.  

It is a fascinating study. “Now, when I see an older person, I don’t look at them as old, I just look at them as someone whose system needs to be rebooted,” Sinclair told Time magazine. “It’s no longer a question of if rejuvenation is possible, but a question of when.” 

Nonetheless, the ability to manipulate aging is no longer in the realm of science fiction – it is now well within the realm of possibility and has revolutionized the way scientists view aging.