26 August 1999
Source: Reuters Health News (with whom the copyright remains)
Experiments in mice suggest that low-calorie diets block the action of genes that trigger cell aging.
"This is a leap in our understanding of how calorie restriction works (to slow aging)," said study co-author Dr. Richard Weindruch, of the University of Wisconsin-Madison. The findings are published in the August 27th issue of the journal Science.
Previous studies have suggested that low-fat, low-calorie diets can extend life spans in animals. In fact, calorie restriction is the only known method of slowing aging in mammals.
To help determine the mechanisms behind this effect, Weindruch and colleagues used sensitive tests to compare up to 10% of the complete genome ('genetic blueprint') of 5-month-old (adult) mice and 30-month-old ('elderly') mice. In fact, study lead author Dr. Tomas Prolla believes that "this study has analyzed more genes with regard to aging than all previous studies."
According to the researchers, the function of about 2% of the genes changed markedly with increasing age. Genes governing cellular responses to injury -- including responses to overheating, normal DNA repair, and oxidative stress (the damage done to cells by byproducts of metabolism) -- nearly doubled in activity.
These results were not surprising, since, according to Prolla, "at the molecular level, normal aging looks like a state of chronic injury."
On the other hand, the activity of genes concerned with energy metabolism, protein repair and biosynthesis fell by half in the 'elderly' versus 'adult.' Each of these processes helps the body maintain normal healthy cellular function.
The investigators then compared age-related changes in gene activity in mice fed calorie-restricted (75% less food energy) diets to those of mice on normal diets.
According to the researchers, the low-cal regimens completely or partially prevented 84% of the major gene changes described above. They speculate that reduced daily food energy intake might lower cellular injury and boost cellular repair mechanisms -- leading to longer, healthier lives -- at least in mice.
In an interview with Reuters Health, Weindruch said these latest findings may help lead to drug therapies that "retard the aging process... on a tissue-specific basis."
He added that he and his colleagues are extending their studies to monkeys placed on a 30% calorie-restricted diet, and they plan similar research in humans, as well.
Weindruch warned, however, that anyone attempting a dramatic reduction in calorie intake do so with caution. He suggests that those "who elect to pursue calorie-restricted diets should work closely with nutrition experts... to avoid malnutrition."
SOURCE: Science 1999;285:1390-1393.
© Reuters News Service
28 August 1999
STEVE CONNOR
© 1999 The Independent, London
Scientists have for the first time witnessed the many genetic changes that take place
during aging and have found evidence to support the idea that low-calorie diets
can extend lifespan.
The findings support the theory that as the body grows old it is less able to repair the
damage caused by a gradual build-up of toxic by-products, such as highly active ``free
radicals'' produced during chemical oxidation within the cells.
It is thought that restricting calorie intake, provided that other nutrients are taken at
normal levels, slows down the production of these toxins, thereby delaying the ageing
process.
Some genes are likely to be responsible for mopping up the toxins before they do much
damage. The latest research is a way of identifying these genes, which could possibly lead
to developing new drugs to augment their activity.
Calorie restriction appears to delay the onset of ageing in part by interfering with the
way genes are switched on or off as people get older, the researchers believe.
By studying changes in the activity levels of about 3,400 genes in laboratory mice fed on
a low-calorie diet, the scientists found that a small percentage of these genes played a
direct part in determining lifespan.
The scientists believe that the work could open the way to new insights into human ageing
and how it can be slowed down by changes in diet and lifestyle, which could have a direct
influence on some genes.
Previous work on rats has indicated that caloric restriction - where the diet has up to 30
per cent fewer calories but normal nutrient levels - can significantly extend lifespan,
although there has not been any direct evidence yet that the same is true for humans.
The latest study by Tomas Prolla, professor of genetics, and Richard Weindruch, professor
of medicine, at the University of Wisconsin-Madison demonstrated that about 2 per cent of
the genes studied were affected by ageing. The genes appear directly to influence the
body's response to such age-related things as stress, tissue repair and energy production.
``This study has analysed more genes with regard to ageing than all previous studies
combined,'' Professor Prolla said. ``At the molecular level, normal ageing looks like a
state of chronic injury.'' Half the mice in the study - published in the journal Science - were placed on
calorie-restricted diets from an early age and their genes showed just how the animals
adapted to the reduced intake of energy.
``This is a big leap in understanding how a reduced-calorie diet works. There hasn't been
much consensus on how calorie restriction retards ageing,'' Professor Weindruch said. ``We
now know which sets of genes that change with ageing are affected by caloric restriction.
We think this technology has led us to a panel of molecular markers of ageing which will
enable use to screen panels of potential anti-ageing drugs.''