Despite much research, the genetic causes why animals have such different longevities remain largely unknown, much because so many factors act on ageing that isolating the effect of a single gene is  almost  impossible.

But now, a study just published in the journal AGE might help to change that as researchers Pedro Magalhães and Yang Li from the Institute of Integrative Biology, at the UK University of Liverpool,  unveil a new method that has already help them to identify several  proteins involved in DNA-repair and in the recycling of abnormal molecules as being linked to longevity. 

The study– which uses an algorithm to identify proteins mutating in parallel with the increase of lifespan – reveals how longevity has been affected by natural selection and gives clues on the key processes behind aging while introducing a method that can now be used to understand the genetics of old age.

In the last decades much work has been done on aging not only because people are living longer, but also because we, as a society, have become obsessed with youth. Despite this we remain very far from understand its genetic basis. In fact, even the sirtuin gene – one of the most promising discoveries in aging research of recent years which led to the launch of several anti-aging products – is now been questioned. The problem is that aging not only affects multiple body functions, but is also influenced by both a variety of genes and environmental factors.

Interestingly, biological and fossil data suggest that longevity has increased continuously during mammalian evolution, and particularly in the lineages leading to humans. This and the fact that evolutionary theory predicts that genes that confer higher longevity would be selected during evolution as long no other major selective pressures occur, led to the idea behind the new study by Magalhães and Li. Their hypothesis was that proteins/genes that determine longevity should be under accelerated evolution in the mammals’ lineages where longevity increased and could be identified through that.

To try to prove this and find genes and biological processes linked to longevity, the researchers  looked for mammals  that had evolved during the path towards humans – so from the initial mammal radiation and over a long period of time –  with very different longevities and a fully sequenced genome (to allow their comparison). 36 species were found and these shared more than 15 thousand proteins, which the researchers then tested. 

After predicting how these proteins first looked in ancestral species, Magalhães and Li developed an algorithm capable of discovering patterns across genomes to find those proteins with accelerated evolution as longevity increased.  They were able to find a number of  “signatures” identifying genes potentially linked to longevity, including some involved in DNA repair and the ubiquitin pathway (that recycles abnormal proteins).

This makes sense as one of the hallmarks of aging is the accumulation of damaged molecules -such as DNA, proteins and lipids - eventually causing the cellular dysfunction and death that underly much of the aging process. Magalhães and Li’s results show that at least some repair systems were selected for, and, arguably, optimized in long-lived species.

As Magalhães explains, “The genetic basis for longevity differences between species remains a major puzzle of biology. A mouse lives less than five years and yet humans can live to over 100 for example. If we can identify the proteins that allow some species to live longer than others we could use this knowledge to improve human health and slow the ageing process. Here we developed a method to detect proteins whose molecular evolution correlates with longevity of a species. The proteins we detected changed in a particular pattern, suggesting that evolution of these proteins was not by accident, but rather by design to cope with the biological processes impacted by ageing, such as DNA damage. The results suggest that long-lived animals were able tooptimise bodily repair which will help them fend off the ageing process.”

Citation: Yang Li and João Pedro de Magalhães, 'Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity', AGE DOI: 10.1007/s11357-011-9361-y