Record increase in life expectancy
A new study on roundworms Caenorhabditis elegans, conducted by specialists of the Institute for the Study of Longevity. Baka, working under the guidance of Dr. Pankaj Kapahi, demonstrated the possibility of a five-fold increase in life expectancy by combining two mutations.
One of the mutations used in the work – a mutation of the Daf-2 gene encoding a receptor for insulin-like growth factor–1 – inhibits the activity of key molecules of the insulin-mediated signaling mechanism, and the second – a mutation of the RSKS-1 gene - inhibits the signaling mechanism mediated by the rapamycin target protein (TOR). According to Dr. Kapahi, RSKS-1 inhibitory mutations usually lead to a 30% increase in nematode lifespan, whereas many Daf-2 mutations double it.
The authors expected that summing up the effects of such mutations would increase the lifespan of worms by 130%, but the observed synergistic effect exceeded all expectations. The combination of the two mutations triggered a positive feedback loop in the cells of the so-called germ line, which includes all the reproductive cells of the body, starting from the primary germ cells and ending with gametes (mature germ cells). The result was a fivefold increase in life expectancy, which in terms of human age corresponds to about 400-500 years.
The researchers suggest that an analog of the mechanism they discovered may also take place in the mammalian body and believe that the next stage of work should be experiments on mice. The idea is to act with the drug rapamycin, which inhibits the TOR mechanism, on mice with an insulin-mediated signaling mechanism inactivated using genetic methods.
Kapahi believes that the data obtained indicate the possibility of using combined approaches to combat aging. This strategy has already proved itself in the treatment of cancer and HIV. Previously, cancer researchers looked for mutations in individual genes, but later it became obvious that the progression of the disease is due to various mutations in a variety of genes. Most likely, the aging process is based on a similar mechanism. This study may help to understand why specialists cannot identify individual genes responsible for the life expectancy of long-lived people. Most likely, these people owe their exceptional lifespan to the interaction between genes.
Article by Di Chen et al. Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans published in the journal Cell Reports.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Buck Institute for Age Research:
Five-Fold Lifespan Extension in C. Elegans by Combining Mutants.
17.12.2013