Death and Taxes

Benjamin Franklin is attributed with saying “In this world nothing can be said to be certain, except death and taxes.” Although intended as a comment on economics, it does mirror a fatalistic view of death and the insurmountability of mortality that has fascinated humanity for centuries. Yet, geneticists are probing the extent to which longevity is predetermined by our heritage and, intriguingly, whether this fate can be altered.

During the Great Depression there was concern over the affect chronic hunger would have on people’s lifespans; consequently scientists decided to deprive rats of food in an effort to correlate this. To their surprise, it was found that rats on a restricted diet lived significantly longer than their well-fed counterparts. From tinkering with worm and fly genetics, it is now known that factors influencing metabolism have a striking effect on an individual’s lifespan.

A particular area of interest is a gene, identified in the Icelandic population in 2002, aptly named the methuselah gene. Subsequent research at Harvard found that all of the centenarians they studied possessed this gene, while their children were likely to live up to 15 years longer than normal. In a laboratory setting, inhibition or over-expression of the gene in insulin producing cells of drosophila flies increases lifespan significantly ¹. Inhibiting, or over-expressing, the methuselah gene decreases the production of the growth hormone IGF-1 and it is this aspect that is believed to increase longevity. This gives some credence to the idea that shorter people may live longer lives – after all smaller breeds of dogs have less IGF-1 than larger breeds and tend to live longer. Yet this mechanism is more nuanced than initially believed; the protein product is very promiscuous with its interactions ², and there appears to be a trade-off with the ability to reproduce.

This gene highlights the importance of metabolism in predicting longevity through genetics, but are we destined to equate cake with death and resign ourselves to a diet of muesli? For those who seek a longer life but don’t want to diet, the drug rapamycin has been shown to significantly extend the lifespan of mice ³. This drug, derived from bacteria found on Easter Island, inhibits the mTOR pathway, which promotes cell growth and proliferation. It is not clear yet whether these effects are due solely to prevention of cancers or have a larger overall effect, i.e. reduced oxidative stress, but research of its mechanisms certainly adds hope to those of us who crave that extra slice of cake.

Edited by Debbie Nicol

1. Arau´jo AR, Reis M, Rocha H, Aguiar B, Morales-Hojas R, et al. (2013) The Drosophila melanogaster methuselah Gene: A Novel Gene with Ancient Functions. PLoS ONE 8(5): e63747. doi:10.1371/journal.pone.0063747 
2.  Ja, W.W., Carvalho, G.B., Madrigal, M. , Roberts, R.W., Benzer, S. (2009) The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. Protin Sci. 18(11): 2203–2208.
3. Harrison, D.E., Strong, R., Sharp, Z.D. et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, vol 460, doi:10.138/nature08221