Sci. Aging Knowl. Environ., 22 January 2003
Unorthodox mitochondria might power extreme longevity
Key Words: homoplasmy heteroplasmy leukocyte granulocyte
Teaching children to look both ways before crossing the street and warning them never to date people like Charles Manson might prolong their lives. But something besides lessons that mothers pass on to their children might exert a bigger effect on longevity: mitochondrial DNA. Compared with the general population, people who survive for a century are five times more likely to harbor a particular version of mitochondrial DNA, according to a new study. The researchers suggest that this variant might enhance survival by speeding mitochondrial reproduction, enabling older folks to replace oxidant-battered organelles.
Mitochondria, the powerhouses that fuel cellular activities, are nonconformists. They harbor their own DNA and sometimes reproduce out of sync with cell division. Unlike nuclear DNA, mitochondrial DNA passes only from mother to offspring. Three years ago, Giuseppe Attardi, a molecular geneticist at the California Institute of Technology in Pasadena, and colleagues found four centenarians who shared a genetic change in a region of mitochondrial DNA that controls DNA duplication, raising the possibility that the alteration extends life.
By analyzing mitochondrial DNA isolated from Italians who were between 18 and 106 years old, Zhang and colleagues have now pinpointed another possible longevity variant in the same area. The sequence at a particular site in mitochondrial DNA can be identical in all of an individual's mitochondria, or it can differ between them. The researchers found that 17% of people between 99 and 106 years of age carried only this variant in mitochondria of their white blood cells. By contrast, only 3.4% of people under 99 showed this genetic uniformity. To probe whether the variant is inherited, the team studied skin cells collected from the same individuals between 9 and 19 years apart. In some subjects, both samples showed only the unusual form, whereas in other individuals, it either appeared or became more abundant during the intervening 10 years. The results suggest that some people inherit the variant from their mother, and others acquire it during their lifetime; in the latter situation, the revised DNA displaces the other mitochondrial variants, says Attardi, a co-author.
The variant's predominance in centenarians suggests that it promotes survival, he says, perhaps by helping people endure the stress of aging. It shifts the point at which the mitochondrial DNA strand starts to duplicate, and this change might accelerate reproduction, allowing the lucky individual to replace damaged organelles faster--for example, those wounded by oxidants stemming from metabolism.
"This is a very intriguing observation," says geneticist Lindsay Farrer of Boston University School of Medicine. "It's one of the first [genetic variants] that shows a robust difference between centenarians and younger folks." Another group, for instance, discovered a stretch of chromosome 4 that is more common in centenarians but hasn't homed in on the precise spot (see "Hints of a "Master Gene" for Extreme Old Age"). However, Farrer adds, further work is needed to nail down how the variant affects survival. Scientists still have a way to go before they understand this lesson of long life.
J. Zhang, J. Asin-Cayuela, J. Fish, Y. Michikawa, M. Bonaf�, F. Olivieri, G. Passarino, G. De Benedictus, C. Franceschi, G. Attardi, Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leucocytes. Proc. Natl. Acad. Sci. U.S.A., 21 January 2003. [Abstract] [Full Text]
January 22, 2003
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Citation: M. Leslie, Century Mark. Science's SAGE KE (22 January 2003), http://sageke.sciencemag.org/cgi/content/full/sageke;2003/3/nw14
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