Prof. Haim Cohen, of the Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, aims to elucidate the mechanism of the molecular regulation of aging.
In the Cohen Lab of Molecular Mechanism of Aging, his research team is investigating two major pathways that have been shown to regulate lifespan – caloric restriction (CR) and sirtuin deacetylases. Studies in model organisms show that the activity of the Sir2 family of NAD+-dependent protein deacetylases (sirtuins) is important in regulating lifespan in yeast, worms, and flies. Overexpression of Sir2 in these organisms can extend their lifespan by approximately 40%, and in some yeast and fly strains, Sir2 mediates the effect of CR on lifespan.
Moreover, Cohen’s team has recently shown that in mammals, SIRT1 and SIRT6, two of the human Sir2 homologues, are induced in multiple tissues upon CR, and mediate the protection of CR from cell death. In 2010, Cohen was awarded a roughly €2 million European Research Council (ERC) Starting Grant for a 5-year study entitled “SIRT6 Activation for Countering Age-Related Metabolic Diseases ( “SIRAID”).
These findings suggest that activation of sirtuins in mammals has the potential to mimic the beneficial influence of CR. In order to achieve this, Cohen’s lab has developed a mouse model known as MOSES (Mice Over-expreSsing Exogenous SIRT6), and found these mice to be protected against the pathological damage caused by obesity. When fed a diet to induce obesity, these mice accumulated significantly less fat, LDL-cholesterol, and triglycerides, and did not develop diabetes. These results demonstrate a protective role for SIRT6 against the metabolic consequences of the 21st century obesity epidemic and suggest a potentially beneficial effect of SIRT6 activation on age-related metabolic diseases. Cohen’s lab is currently focusing its efforts on identifying small molecules that can induce SIRT6 activity in order to develop drugs against age related metabolic diseases.