Scientists reprogrammed mice's genes to live longer, and it worked!

One of the study authors and Chief Scientific officer at Rejuvenate Bio, Noah Davidsohn told MIT Technology Review, “This is a powerful technology, and here is the proof of concept. I wanted to show that it’s actually something we can do in our elderly population.”

The secret to increasing mice lifespan

When individual mature (old) cells are exposed to proteins or genes that are found in early embryonic stages. They start behaving like young stem cells, this process is called genetic reprogramming. Japanese researcher Shinya Yamanaka came up with this intriguing gene therapy approach and was awarded the Nobel Prize in Medicine for this in 2012. 

Many scientists in the past have shown that cells can rejuvenate through gene therapies that involve reprogrammed genes. However, rejuvenating animals like what’s done by the current study authors is a rare feat. Davidsohn and his team somehow brought mice cells back to a younger state, and by mice cells, we mean the whole mice bodies.

In laboratory settings, mice can survive up to three years, all the mice tested by the Rejuvenate bio team were already about two and a half years old (124 weeks). The researchers put their mice into two groups; the first group contained mice that didn’t receive any gene therapy. Whereas mice in the second group were injected with three reprogrammed genes. 

All the members of the control group died after nine weeks, but surprisingly, the mice in the second group were still alive. Moreover, they managed to survive another nine before actually succumbing to death. The reprogrammed genes enabled the animals in the second group to live twice (18 weeks) as long as the ones in the control group (nine weeks). 

The problem with reverse-aging

This life-extending gene therapy is special because, unlike other anti-aging methods, it acts as a one-time solution. For instance, in 2016, a team of researchers proposed that a drug called rapamycin can increase the lifespan of middle-aged mice. That sounds like a perfect solution, right?

The problem with rapamycin or other such drugs is that they are required to be taken throughout life and cause several harmful side effects in mice. If they are not even safe for animals, how can they be considered for human usage? 

Genetic reprogramming, on the other side, is only done once, and its effect is long-lasting. This is why the researchers believe that it could emerge as a suitable reverse-aging solution

“Based on our novel proof-of-concept studies in an extremely aged mouse population (equivalent to >80 years of age in humans) and previous studies in younger mice, we envision therapeutic rejuvenation in aging humans, first in specific age-related disease settings and later for therapeutic healthspan and lifespan extension,” the authors note in their study.

However, many scientists warn that genetic programming can also lead to cancer. Therefore, before this approach is considered for full body rejuvenation or life extension, it should be fully understood. 

The authors argue they need to conduct further research and carefully monitor animal studies before the treatment is adopted for humans, but they didn’t notice any tumor formation during their experiment. 

They believe their research along with other advanced techniques, could one day allow the safe delivery of partial rejuvenation therapies in humans. 

The study is yet to be peer-reviewed and is currently available on bioRxiv.

Study Abstract:

Aging is a complex process best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. While aging cannot currently be prevented, its impact on lifespan and healthspan in the elderly can potentially be minimized by interventions that aim to return these cellular processes to optimal function. Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; OCT4, SOX2, and KLF4; OSK) can reverse age-related changes in vitro and in vivo. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild type mice. Here, we show that systemically delivered AAVs, encoding an inducible OSK system, in 124-week-old mice extends the median remaining lifespan by 109% over wild-type controls and enhances several health parameters. Importantly, we observed a significant improvement in frailty scores indicating that we were able to improve the healthspan along with increasing the lifespan. Furthermore, in human keratinocytes expressing exogenous OSK, we observed significant epigenetic markers of age-reversal, suggesting a potential reregulation of genetic networks to a younger, potentially healthier state. Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.