This fascinating review Vijg and Campisi discusses question, which may be of interest to all of us, that is whether or not it is possible to extend life expectation. Slowly life expectations is increasing with a target of 120-125 years being seen as possible though at the moment 85 years is a good possibility for many.
Experiments in the nematode show that mutations in single genes can extend life expectation. Most of the 100 or so genes so acting act in evolutionarily conserved pathways that regulate growth, energy metabolism, nutrition, sensing and reproduction eg insulin growth factor (IGF-I ) signalling (IIS) pathway and mitochondrial electron transport chain. Extension of life occurs when activity is reduced, perhaps reducing somatic damage and increasing somatic maintenance.
In mammals mitochondria play a part in signalling apoptosis which has a role in longevity. Also FOXO ( forkhead transcription actors) and silent information regulator ( SIR) protein deacetylases ( sirtuins ). Some FOXO proteins initiate apoptosis which removes dead cells . FOXO proteins also upregulate antioxidant defences.
Many of these pro longevity mutations mimic dietary restriction which increases longevity in many species. Though reduced food intake may act through different mechanisms. It is suggested that small molecular weight molecules would be effective eg polyphenolics such as resveratrol and fisiten, the antifungal agent rapamycin. Glucose metabolism is a key target for current research seeking life extending mechanisms. Vitamin anti-oxidants isolates have had little benefit in this respect.
Maybe optimal conditions for life prolongation are necessary and the results from animals are very species dependent eg dependence upon aerobic respiration.
The process of ageing and why we die is not understood and clearly complex. Also it is useful to differentiate between ageing and disease. Cancer is a case in point which again is species dependent in occurrence. Ageing is influenced as with all biology , by genes and environment.
Vijg and Campisi 2008 Puzzles, promises and a cure for ageing Nature vol 454 pp 1065-71

Martin Eastwood
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