Longevity Briefs: Do Genetics Studies Really Help The Fight Against Ageing?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Twin studies suggest that somewhere between 25% and 30% of the variance in human lifespan can be explained by genetic factors. It was once thought that the way in which an organism’s genes determine its lifespan must be very complicated, but we now know that isn’t necessarily the case. Research in animal models has shown that a variant or mutation in a single gene is sometimes enough to significantly increase an animal’s lifespan. There are now over 1000 genes that have been associated with longevity in various animal species, and some similar genes have been identified in humans. Yet despite this, it’s still not certain whether this knowledge will lead to treatments that extend human health or lifespan.

What did the researchers do: In this article, researchers review what we know about the genetics of ageing in humans. They discuss the genes currently thought to be important for human longevity, as well as the methods used by scientists to identify them.

Key takeaway(s) from this research: While animal studies can point us in the right direction, much of what we know about the genetics of lifespan in a given species will not translate to humans. Advances in genome sequencing and the existence of large genetic databases like the UK Biobank have allowed scientists to identify many human genes associated with longevity, but only four of them are well established as reliable determinants of human lifespan. They are:

• APOE: A gene that affects cholesterol and lipid transport. It’s important for the repair of cells in the brain. Variants of APOE have a strong effect on one’s risk of developing Alzheimer’s disease.
• FOXO3А: A gene that affects many processes thought to be important in ageing such as DNA repair, cell division and ‘cell suicide’ (apoptosis).
• CDKN2B-AS1: A gene whose variants contribute to one’s risk of cardiovascular disease and cancer.
• The 5q33.3 locus: A gene whose variants affect blood pressure and risk of cardiovascular disease.

These genes explain only a small fraction of the 25%-30% heritability mentioned earlier. Why hasn’t the search for human longevity genes been more successful? According to the authors, there are a few reasons. Genome-wide association studies (a method used to identify important genetic variations by comparing the genomes of many people) are our main source of knowledge concerning the genes associated with human longevity, but they often use different methods which make it hard to combine the results of multiple studies together. These studies also aren’t very good at detecting genetic variants that are very rare. In the future, researchers will increasingly use so-called ‘multi-omics’ – an approach to studying biology in which a system is studied from many different angles, looking simultaneously at the genes, proteins, epigenetic changes and metabolic differences associated with human longevity. This will help give us a more complete picture of what really matters when it comes to human ageing, as well as how we might be able to slow it down.