SIRT6: The protein that talks the talk and walks the walk

Nir Barzilai on keeping longevity research relevant to humans, developing gerotherapeutics and making the best decisions.

Last month, US-Israeli startup SIRTLab announced the appointment of leading geroscience researcher Dr Nir Barzilai as its Chief Medical Adviser, adding additional longevity kudos to a company founded by Boaz Misholi and Professor Haim Cohen, a world leader in research of SIRT6, who has seen over $40 million invested in his research.

Longevity.Technology: SIRTLab has the development of therapeutics that boost levels of SIRT6 in its sights, and given that SIRT6 has been shown to protect against aging-associated pathologies, including metabolic disease and cancer, and to promote longevity [1], it is no wonder that SIRTLab styles itself as “focused on longevity”. The company includes liver disease, frailty, metabolic syndrome, neurodegeneration and inflammatory conditions among its targets, and we grabbed some time with Nir Barzilai to find out more about his hopes for SIRT6 and how SIRTLab is moving forward.

Nir Barzilai on…

Excitement about SIRT6

It’s not only talking the talk, but it’s walking the walk. Having previously given advice unofficially, I am now on the Board and fully behind SIRTLab – this due to the new evidence and new technologies at play, and that excites me from a scientist’s perspective. In my centenarian study we found functional mutation in SIRT6 gene that, for me, completed the story from mice to humans – and this is important. In 2021, two-thirds of the drugs approved by the FDA were based or supported by genetic discoveries in humans. Previous drug development has been too focused on young mice and, as a result, has failed too often. What SIRTLab is doing is going to be very relevant to humans.

When developing a gerotherapeutic, the aim is to target the biology of aging and prevent age-related diseases, but in reality, this means every longevity biotech is finding diseases that can treated specifically by a gerotherapeutic drug which can be repurposed. “Disease” drugs can also be good for investors from a patent point of view.

We will target a condition and hopefully by targeting this condition, we’ll be able to repurpose this drug for other uses. Although there are various options, the obvious one is NASH (nonalcoholic steatohepatitis), and SIRTLab has numerous models for this.

Special delivery

One of the exciting things about SIRTLab is that it is using mRNA tech to deliver the mRNA for SIRT6 with a lipo-particle to the liver. By delivering these particles to the liver, action is fostered, not only in the liver, but acting on other conditions. While I can’t say too much, triggering expression of SIRT6 in the liver, which then talks to other organs, including the brain, muscles and other organs, has a systemic effect. Having several indications makes this approach, to my mind, very exciting at this time.

We’re not completely decided on NASH, and we need more studies on other indications, but we’ll make the best decision for science, for longevity and for the investors.

Into clinical trials

I would imagine we’ll start with short trials – a week or possibly two – that deliver our drug to volunteer patients in hospital (half drug, half placebo) who are going to undergo surgery. Post-operation, we’ll monitor recovery, looking at appetite, complications, body weight, length of stay and mental state. Short trials mean accelerated progress. There’s a commercial angle, of course, but as a clinician I am focused on drug improvement – and if we show the drug is working the way that we want it to work, then there are opportunities beyond the FDA.

READ MORE: Does SIRT6 hold the key to human longevity?


Photograph: Zffoto/Envato