Mutations in Cells Are Linked to Aging
Caltech scientists report some of the most convincing evidence yet that aging is tightly linked to genetic mutations in the small compartments where cells manufacture their energy.
The results, published today in the journal Science, lend strong support to a decade-old theory of how people age that centers on mitochondria, the tiny power generators in all cells.
The theory proposes that aging is triggered as mutations in mitochondria impair their ability to make energy while at the same time turning them into producers of toxic free radicals. The result is devastating: low in energy and full of toxic molecules, the cell ages as it essentially runs out of steam.
But although scientists already knew that mitochondria deteriorated with age, the source of the damage had proved elusive. Previous studies had only found very few mutations in the mitochondrial DNA of old cells. And because mitochondria constantly mingle with other cellular components, skeptics contended that the source of mitochondrial deterioration could come from surrounding cellular material and not the mitochondria themselves.
Now, Giuseppe Attardi and colleagues from Caltech and the University of Milan are the first to uncover a significant number of genetic defects in a unique region of the mitochondrial DNA of old humans, but not young ones. The results support the idea that mitochondrial defects--and subsequent aging of the cell--may very well start within the mitochondria.
“This is a nice piece of work that goes hand in hand with the mitochondria theory of aging,” said molecular biologist Vilhelm Bohr from the National Institute on Aging.
According to Attardi, skeptics might be surprised by the result, which underscores the significance of mutations in mitochondrial DNA.
“This has been a controversial field, but now [this study] places mitochondria very clearly as a possible player in aging,” Attardi said.
Although the findings are far from providing the sought-after secrets for the reversal of aging, the study will help scientists focus on more basic questions about the role of mitochondria in aging.
“The next step is to find out what is causing these mutations and their effects on cells,” Bohr said.
Attardi and his colleagues looked at an important control region of the mitochondrial DNA that is needed to produce more DNA copies. Because this region is more exposed to DNA-damaging free radicals, the team reasoned that it might be a place where mutations could accumulate.
The scientists sampled cells from 18 randomly picked, unrelated people of all ages: from a 20-week fetus to two 101-year-olds. The researchers also analyzed cells from nine other people from whom samples had been taken once at a younger age and another time 15 to 19 years later.
Using sensitive detection techniques, the scientists discovered that 10 of the 14 individuals older than 65 had a high number of specific mutations in their mitochondrial DNA. Those mutations, in contrast, were absent in all 13 people younger than 65.
The mutations were also abundant, affecting up to 50% of the mitochondrial DNA from older individuals.
Evidence that these mutations had accumulated over time came when the team analyzed those samples taken from the same person within a 15- to 19-year lapse. In three of the nine people, mutations were very low in the sample taken at a younger age, but had become abundant at a later age.
Largely ignored by biologists for many years, mitochondria are emerging as key players in events such as cancer, cell death and now aging. The new study is one more piece of evidence that these energy stations the size of a bacterium--present in numbers of about 10,000 per cell--play important roles in major biological events.
“The field of mitochondrial genetics is now booming,” Bohr said. “Before, mitochondria had been on the back burner.”
Attardi stressed that it is still too early to say whether the mutations themselves cause aging, and that all his team has uncovered so far is a strong link between these abundant mutations and cells that get old.
Furthermore, the phenomenon was observed in only one kind of human cell, so studies should focus on whether this is a widespread phenomenon in all cell types, Attardi added.
“The results are an interesting observation, but they should be repeated with isolated tissue from other sources,” said molecular biologist Kenny Beckman of UC Berkeley. “What happens if you take chunks of brain, or liver, or lung? Will you see the same effect?”
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A Link to the Aging Process
A group of scientists from Caltech and the University of Milan are the first to uncover a significant number of genetic defects in a unique region of the mitochondrial DNA of elderly humans, but not young ones. The results support the idea that mitochondrial defects and subsequent aging of the cell may very well start within the mitochondria, the tiny power generators in all cells.
Sources: Science magazine and other scientific studies
