The biochemistry of growing old

THE phenomenon of senescence or aging is one of those problems that - as Mark Twain said about the weather - everyone talks about but no one does anything to solve. A number of experiments carried out on animals suggest that we may age because we burn ourselves up. As a result of our actions, we appear to generate highly active oxygen radicals in our tissues, thereby oxidising - 'burning' - the essential molecules necessary for thesupport and maintenance of life processes. This hypothesis gains increasing support as a result of research carried out by Sanjiv Agarwal and Rajinder S Sohal of the Southern Methodist University, Dallas, us (Proceedings of the us National AcademY of Sciences 91).

Agarwal and Sohal worked with males of the housefly Musca domestica. They established that the life span of a male Musca depends inversely on how active it is: flies that were housed in small bottles in which they could only walk lived more than twice as long on an average as flies that were permitted to fly freely (58 days vs 21 days). In both lots of flies, aging was accompanied by oxidative damage to DNA as measured by the accumulation of the molecule 8-hydroxy deoxyguanosine (9-OHdg) which is formed upon oxidation of the normally occuring compound guanosine.

After discounting for the shorter life span of fliers when compared to walkers, the levels of 8-OHdg built up at the same rate in all flies. In other words, oxidative damage Of DNA is related to ph.vsical activity and to physiologi age, not chronological age. The ad related increase in 87-OHdg concenle tion was matched by age-related oxi tive damage in proteins.

Interestingly, the bulk of the daing was in mitochondrial DNA and nuclear DNA. Direct application is called oxidative stress ' meant exposure to an environment enrichea oxygen or to X-rays (which are kno to generate reactive oxygen speci mimicked this finding: both treatmen led to an increase in 8-OHdG content and in both cases the increase was roughly 3-fold more in mitochondrial DNA than in nuclear DNA.

The obvious conclusion from the study is that in houseflies, there is an inverse r&ationship between the extent to which DNA is damaged on account getting oxidised and life expectaro Similar observations have been previously on mammals. The new point made by this work is its highlighting of damage to mitochondrial DNA as the significant correlate.

But is oxidative damage Of DNA a cause of aging or merely a by-product? Logic indicates that it might be a factor responsible for our growing Besides, an earlier study by W C and Sohal has shown that the life spa the fruitfly Drosophila melanogaster can be extended by over-expressing genes that encode the proteins superoixide dismutase and catalase, enzymes that act to remove highly reactive oxygen species.

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