Mice experiments support an alternative theory of ageing, the scientists report in Friday's issue of the journal Science (vol 309, issue 5733, pp81-4).
This theory, previously raised by other groups, suggests that an accumulation of genetic mutations in cells leads them to die off resulting in malfunctions that show up as age-related changes in the body.
In contrast, there was no evidence of oxidative stress, or the process of oxidation that is thought to lead to damaging molecules called free radicals. Antioxidants have been marketed to counter this phenomenon.
Both theories of ageing are however based on damage to the cell's genetic material -DNA.
The new study suggests that ageing occurs, in part, as mutations build up in the DNA of the cell powerhouses, mitochondria, which in turn triggers the death of critical cells that lead to such things as hair and weight loss, hearing and vision impairment, loss of muscle mass, weakened bones and fewer circulating red blood cells.
"We think that the key to what is happening in ageing is that as (genetic) mutations or DNA damage accumulates, critical cells die," said study leader Tomas A. Prolla, a geneticist at the University of Wisconsin-Madison.
"These experiments favour a major role for programmed cell death in ageing."
The researchers used mice genetically altered to have a deficiency in a protein that proofreads mitochondrial DNA for mistakes. They therefore accumulate genetic mutations at a higher rate than unaltered mice.
Prolla's team saw that programmed cell death, known as apoptosis, was greatly accelerated in this group, with obvious hallmarks of ageing such as hair loss and atrophied muscle and bone occurring much faster than the typical laboratory mouse.
Markers of oxidative stress did not parallel the accumulation of mitochondrial genetic mutations. In fact, the team noted less oxidative stress in some tissues - the liver, for example - which suggests that accumulated genetic mutations in mitochondria slow metabolism.
In turn, that change prompts cells to produce fewer of the reactive free radical molecules, they report.
The symptoms of ageing become pronounced with the loss of some critical cells, notably adult stem cells from some tissues and that are essential for replacing cells that die.
"If these stem cells are lost, tissue structure and the ability of tissue to regenerate are impaired," Prolla explained. "We have observed that in tissues like bone marrow, intestine and hair follicles."
He added that new studies of mice engineered to have improved mitochondrial function may pave the way for investigations into ways to retard ageing.