A 500-year lifespan - dream or reality?

Cell Reports online published the results of a study in December on the worm C. elegans, conducted by scientists from the Buck Institute for Research on Aging, which showed significant promise in terms of longevity. Extending human lifespan five-fold has so far been just a dream … but what if that dream were to become reality?

The aging process can be moderated by genetic and environmental factors. Changes in the insulin signalling (IIS) and Target of Rapamycin (TOR) pathways, various reproductive system signals as well as dietary restriction can all significantly affect lifespan.
In the worm C. elegans, the Californian researchers thus succeeded in genetically inhibiting :

- Key molecules involved in insulin signalling (IIS) such as IGF-1
- The signalling pathway Target of Rapamycin (TOR), which regulates cell proliferation, growth, mobility and survival.

Single mutations in the TOR gene usually result in a 30% extension in lifespan, while mutations in IIS often lead to a doubling of lifespan; added together, they should thus be able to extend longevity by 130%. However, according to the study’s lead author: “Instead of that, what we have here is a synergistic five-fold increase in lifespan”; “the two mutations triggered a positive feedback loop in specific tissues that magnified lifespan. Basically, these worms lived to the human equivalent of 400 to 500 years”.

He suggests that it might not be down to a single longevity gene but to several interactions and synergistic actions between these genes, as has been shown in cancer and HIV research. “In early studies, cancer researchers focused on mutations in single genes, but it became obvious that different mutations in a class of genes were driving the development of the disease” . And it’s likely to be the same case with aging.
This study could therefore explain why scientists are having difficulty in identifying single genes that enable certain people to live to a hundred. “It is highly likely that interactions between genes are critical in those fortunate enough to live long, healthy lives”.

The Buck Institute is the US’s foremost independent research institute dedicated to gerontological science - the link between normal aging and chronic disease. It applies a unique interdisciplinary approach in which laboratories studying the mechanisms of aging combine with those concentrating on specific diseases. Its scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s, cancer, cardiovascular disease, AMD, osteoporosis, diabetes and stroke.

Longevity specialist and lead author of the study Dr. Pankaj Kapahi, who joined the Buck Institute in 2004, has already highlighted the key role played by diet in aging and age-related diseases. Investigating molecular mechanisms in a quest to extend healthy lifespan, he has already demonstrated that a low-protein diet can extend the life of the fruit fly by stimulating mitochondrial energy production, an effect mediated by the growth signalling TOR pathway which is involved in cancer and diabetes. He was the first to show that the TOR pathway has a direct role in the effects of dietary restriction.

He and his team plan to repeat this same combined-therapy test on small mammals - mice that have been genetically modified to suppress the insulin signalling pathway, and subsequently treated with rapamycin, a drug known to block the TOR signalling pathway - to see whether they react in the same way as the C.elegans worms.

For the time being, there are completely natural substances available that scientific research shows can also inhibit precise concentrations of the mTOR gene (mammalian target of rapamycin). These natural rapamycin analogs or “Natural Rapalogs” are curcumin, green tea EGCG, resveratrol fisetin and salicylin extracted from white willow.

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Source :
Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans. Publishing online December 12, 2013 in Cell Reports. Volume 5, Issue 6, 26 December 2013, Pages 1600–1610