Extending longevity

We all (well, most of us) desire to live longer. Longevity is the subject of many a research project and we count Valter Longo among the better-funded scientists studying what influences might result in a longer-lived organism. He likes to work with saccharomyces cerevisiae or common baker's yeast.

Yeasts are single-celled organisms that reproduce by budding. They appear more like bacterial cultures than molds. Yeasts do not produce the branching, threadlike vegetative parts called mycelia common to fungus. The average lifespan of a normal yeast organism is about a week. By knocking out two genes in common baker's yeast -- the RAS2 and SCH9 genes -- and by placing the yeast culture on a calorie- restricted diet an experiment by a team under Longo of the University of Southern California has resulted in extending the life span of the yeast sample by a factor of ten. The RAS2 and SCH9 genes promote aging in yeast and cancer in humans.

The discovery in a preliminary form was first reported in May, 2003 and picked up in an article by physorg.com today and which reports that a paper on the study is scheduled to appear in the Jan. 25 issue of the journal PLOS Genetics. A more comprehensive article on Longo's ongoing research was published in November, 2005 by Science Daily.

In addition to the two afore-mentioned genes, USC studies of the SIR2 gene have suggested that that gene actually promotes aging, although it was previously reported that multiple copies, or "overexpression" of the gene act in exactly the opposite manner, promoting longevity in yeast, worms, and fruit flies. Longo's group simply knocked that one out too. The yeast cells then underwent an adaptation Longo characterized as 'extreme survival mode' when the genes were knocked out, a state wherein they no longer reproduced and in which they exhibited increased protection against cell damage as well as improved DNA repair when placed under stress. They became highly resistant to everything. Important to the whole process was the calorie-restricted diet which the yeast cultures were subjected to. The extreme survival mode of the yeast cells was induced by their near-starvation. Life span in the 2005 study was reported to have increased sixfold. The interesting factor in these experiments was the intuitive sense that Longo applied to his reasoning for knocking out the SIR2 gene and having his previsionary insight realized. He suggested that SIR2 has too many similarities with another gene called HST1 which negatively regulated the protective genes and therefore would ultimately be counterproductive to increasing longevity when combined with a calorie-reduced diet.

The next phase of Longo's research involves similar studies on mice. Much work needs to be done before anti-aging therapies based on this work become available to the general population. Longo cautions that longevity mutations come with severe growth deficits and other health problems. Humans with mutations analogous to those described in the studies exist in a population found in Ecuador. Those with two copies of the mutations exhibit short stature and growth defects but those with one copy appear normal. A study of the normal group will reveal whether those people enjoy longer than average lifespans as well as other health benefits.

Valter Longo's studies have been well-funded by such groups as the American Federation for Aging Research, the National Institute of Aging, and the National Institutes of Health.