Possible anti-aging drug
of a protein that can dramatically extend lifespan, opening up the
possibility of a new 'anti-aging' drug.
Researchers at the Wistar Institute discovered that a molecule called nicotinamide, a component of vitamin B3, or niacin, binds to a sirtuin protein and prevents it from unleashing its anti-aging effects. A drug that prevents the niacin-sirtuin interaction could effectively activate sirtuins and might also help counteract age-related disorders, including obesity and Type II diabetes.
In recent years, the discovery of sirtuins invigorated several biotech companies, which are searching for drug candidates that can boost sirtuin activity. The public health and economic benefits of an 'anti-aging' drug would be substantial.
"Our findings suggest a new avenue for designing sirtuin-activating drugs," said Dr Ronen Marmorstein, a professor at Wistar.
"The jury is still out as to whether a drug of this kind might result in longer life in humans, but I'm equally excited by the possibility that such interventions might help counteract age-related health problems like obesity and type II diabetes."
The Marmorstein group are now planning to develop a drug that can fill the sirtuin binding site and prevent nicotinamide from attaching to it.
"Many drugs have unwanted side effects because in addition to the intended target, the drugs also hit other biologically active molecules that you don't want to affect," said Prof Marmorstein.
"This nicotinamide-binding site we've identified appears to be unique to the sirtuins, so that if we're able to design a molecule to target it, it should be very specific for these sirtuin molecules."
Two Massachusetts-based companies are working to develop drugs that modulate sirtuin activity. Of the seven human sirtuins, Elixir Pharmaceuticals has over twenty patents and patent applications related to the Sirtuin class of compounds, including SirT1 activators and inhibitors. SirT1 is the human equivalent of Sir2, a gene identified in yeast that plays a key role in the control of lifespan, metabolism, resistance to stress and other cellular regulatory pathways.
Sirtris Pharamceuticals has also developed small molecules that are initially designed to activate SirT1. Its lead drug candidate is currently in Phase Ib trials.
Prof Marmorstein has also studied whether the link between longevity and calorie-restricted diets is related to sirtuin enzymes.
"People have known for some time that low-calorie diets result in life extension in many organisms, but they didn't know why. Recent research has shown that the connection works at least in part through these sirtuin molecules."
