Towards SIRT6 Upregulation as a Calorie Restriction Mimetic Strategy

Researchers have in recent years expressed a growing interest in the role of sirtuin 6 (SIRT6) in the mechanisms of calorie restriction and improved function that occurs in response to mild stress. Many forms of stress, such as lowered levels of nutrients, produce benefits via upregulation of cellular maintenance processes such as autophagy.

That said, it is unclear as to whether calorie restriction mimetic therapies will prove to be all that interesting as a class of therapy in humans, as calorie restriction only produces significant gains in life span in short-lived species. While scientists are far from a full accounting of how exactly the sweeping metabolic changes induced by calorie restriction lead to slowed aging, it is reasonable to think that long-lived species are long-lived precisely because many of the important changes induced by calorie restriction in short-lived species such as mice are already activated all of the time in long-lived species such as our own. Thus calorie restriction increases mouse life span by 40%, but it certainly doesn't do that in humans.

US-Israeli startup SIRTLab is focused on the development of therapeutics that boost levels of a key protein called sirtuin 6 (SIRT6), which is heavily implicated in longevity. It appears that high levels of SIRT6 also boosts physical performance and improves memory and cognitive function, even in young mice. By generating mice with overexpression of SIRT6, researchers have demonstrated average lifespan extension of 30%, and positive impacts on frailty. But, while the longevity and healthspan benefits of SIRT6 are well-known, no one has yet developed a therapeutic way to increase SIRT6 levels.

Of course, therapeutic approaches that have worked in animal models don't always translate into results in humans, but SIRTLab believes that SIRT6 expression has a good chance of delivering on its promising results in mice. SIRTLab has created a SIRT6-focused therapeutic platform, with multiple approaches to increasing SIRT6 levels in cells. "We have developed four different ways to therapeutically target SIRT6 production: messenger RNA (mRNA), small molecules, adeno-associated viruses (AAVs), and antagonists for microRNAs that control SIRT6 levels. There are different benefits to each approach, and it's even possible that a treatment could use a combination of two or more. We've seen in our experiments that our mRNA therapeutic boosts cellular levels of SIRT6 by 20 times, which is very exciting." The company hopes to commence its first human trials in 2024, after it completes toxicity studies this year.



Ah.. D. Sinclair's former postdoc Haim Cohen tries the same sirtuin scam that made his mentor rich.

Posted by: Jones at May 23rd, 2023 7:58 AM
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