It is well established that reducing food intake increases life expectation.
Studies of longevity in simple organisms have helped an understanding of how caloric restriction might increase life-span. In the budding yeast Saccharomyces cerevisiae, nutrient withdrawal extends longevity through a pathway that requires the enzyme Sir2. Overproducing this enzyme can prolong the life of yeast grown under normal nutrient condition-. Similarly, in the evolutionary more advanced worm Caenorhabditis elegans, increased expression of the worm’s version of Sir2 has also been shown to extend lifespan.
The Sir2 enzyme belongs to a large family of evolutionary conserved molecules called sirtuins. In lower organisms, such as yeast and worms, these enzymes regulate a wide range of cellular activities that affect lifespan, including modulating how tightly DNA is packaged inside cells.
In mammalian cells, sirtuins act as regulators of programmed cell death and differentiation (cell maturation). Sirtuins exert their effects on these cellular processes by removing acetyl groups from specific target proteins. Deacetylase function depends on the intracellular concentration of nicotinamide adenine dinucleotide (.NAD), and the oxidized form greatly enhances Sir2 activity. In yeast, caloric restriction may regulate Sir2 activity, and hence prolong life, by shifting the ratio of oxidized to reduced NAD or by altering the level of the NAD derivative nicotinamide . Together, these findings suggest a potential mechanism by which metabolic activity and lifespan might con-verge.
Building on the knowledge that caloric restriction prolongs longevity through Sir2, Howitz et al searched for a small molecule that could activate this enzyme directly. These investigators discovered two related compounds that each stimulated Sir2 activity. Both compounds belong to a family of polyphenols secondary metabolites in plants. One uf the most widely studied of these compounds is resveratrol ,a plant polyphenol that is abundant in red wine . and is the most potent Sir2 activator of all of the plant polyphenols tested. The authors showed that this chemical prolonged the lifespan of yeast by approximately 70%.
The concentration-dependent effects of resveratrol as observed by Howitz et al /, were complicated. At relatively low doses these molecules stimulated sirtuin activity, but, at least in certain assays, higher doses had the opposite effect. This is not an ideal character­istic for a pharmaceutical drug. Second, and more importantly, life extension in yeast is a long way from life extension in higher organ­isms. Indeed, how sirtuins function in mammalian ageing is not yet known.
All of which illustrates a fundamental difference between those who would have us following a pharmaceutical path to longevity or a dietary. A diet containing a wide range of plants varied each day may well appeal to nutritionists. In contrast to a fast food diet and pills. The latter would appeal to the Pharmaceutical industry to food related route to agriculture and nutrition.
Finkel T Nature 425, 11 September 2003, pp 132 – 133
Howitz KT et al 425, 11 September 2003 191-196

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