By Travis, John
Science News , Vol. 166, No. 2
With one look, you can usually tell whether someone is old or young. Wrinkled skin or smooth. Thinning hair or thick locks. Bifocals or Ray-Bans. These are just a few of the overt clues. Far less obvious are the age-related signs that show up on the molecular level Ask a geneticist where to look and he may point you to a person's mitochondria. These rod-shaped residents of an animal cell provide the cell with energy, and each mituchondrion has its own DNA strand, which is distinct from the DNA in the chromosomes that dwell in the cell's nucleus. With age, this mitochondrial DNA (mtDNA) becomes riddled with mutations, both subtle and severe.
This observation, made in many species, has prompted some researchers to conjecture that the increasing burden of mutations in mitochondrial DNA is a cause of aging. The majority of researchers have thought otherwise. They argue that the mutations are molecular consequences of aging, akin to wrinkles and graying hair.
"You get more gray hair as you get older, but nobody thinks aging is caused by gray hair," says NilsGoran Larsson of Karolinska University Hospital in Sweden.
Recently, however, Larsson and his colleagues have genetically engineered mice to develop mtDNA mutations faster than normal. Compared to typical lab mice, these rodents suffer age-related conditions, such as hair loss, osteoporosis, anemia, and infertility, much sooner than typical mice do, and they die young. Many scientists hailed these results, reported in the May 27 Nature, as a vindication of the mitoehondrial theory of aging.
"We have been waiting for many years for experimental evidence like this.... It is a fundamental advance in aging research," says David Samuels of Virginia Bioinformaties Institute in Blacksburg.
Samuels finds the new report especially credible because several of its authors, including Larsson, have been publicly skeptical about the hypothesis that mtDNA mutations play a leading role in aging. For example, in a commentary in the February 2003 Aging Cell, Howard T. Jacobs of University of Tampere in Finland challenged the evidence implicating mtDNA mutations.
But the prematurely aging rodents have made him rethink his position.
"I must admit that our findings are provocative," says Jacobs. "The hypothesis that I confidently expected would fall, did not ... The mtDNA mutation theory of aging emerges from all this with something of a feather in its cap."
Some scientists aren't waiting for further confirmation. They're already exploring ways of countering the potential effects of the decay in mtDNA. A few researchers have even proposed genetically engineering people to make their mtDNA less prone to mutations.
CELLULAR LIAISONS At some early point in the history of life, two microscopic cells--most likely different kinds of bacteria--apparently struck a complex bargain. One provided a safe, comfortable home inside its own cellular membrane. In exchange, the new tenants produced extra energy for the host cell. The enveloped microbes gradually shed their distinct identities and became what now are called mituchondria.
Mitochondria are the power plants of an animal cell. Some energy-hungry cells, such as those in muscles, contain up to a thousand of these remarkable organelles. Instead of making electricity, as conventional power plants do, mitochondria use oxygen and complex sugars in a process known as respiration. The product is an energy-rich molecule, adenosine triphosphate (ATP), which cells use to drive myriad chemical reactions. Without ATP, cells would be powerless and die.
Amitochondrion's minuscule anatomy incorporates more than 1,000 different proteins, but most of the genes encoding them have moved into the more sheltered environment of the cell's nucleus. Remaining within the mitochondrion itself, however, is a small loop of DNA harboring 13 assorted genes. It is this DNA that some researchers suspect may hold the keys to aging. …