The Role Of Genomics In Healthy Longevity
Image: Unsplash
No-one now doubts the role of genomics in personalised medicine, particularly the selection of the right treatment for cancer and the 6000+ rare diseases. This role will increasingly spread to other diseases, as we unravel how the genomic profile of the patient defines the exact disease they have. Type 1 diabetes is an example – some children with Type 1 symptoms turn out, on genomic analysis, to have easily treatable versions, avoiding lifetime insulin. But how will genomics play into our healthspan efforts? To what extent will genomics influence “precision prevention” or early personalised intervention”?
Genomic profiling of supercentenarians provides interesting insights into these lucky individuals, with stronger immune systems, less oxidative stress, stronger DNA repair mechanisms and protective variants against age-related diseases. However, we are still some way from being able to replicate their genomics in the rest of us! What can we learn from genomics that can have broader application?
I see three main thrusts. Firstly, discovering disease predisposition. The UK is working hard to exploit its huge investment in genomics, as its programme goes beyond its initial focus on cancer and rare disease patients to include increasing numbers of the 500,000 subjects in the - initially healthy - UK Biobank population. And it is going further to explore genomic sequencing on newborn babies – to take the identification of future disease from a small heel-prick of blood, from a small handful of conditions to several hundreds. As Richard Scott, head of Genomics England, put it to me, the “lifetime genome” will not only give us a steer on future disease risk, it will guide us on the pharmacogenomics that will determine which drug and drug combinations to take, and which to avoid.
One practical possibility that I am working on, with My Gene Trait, a UK-based company, is to build an AI-powered personalised skincare platform drawing on genomics and lifestyle factors to help select the most appropriate skincare products. Most users of a skincare brand that were surveyed were open to such a concept, so that understanding the genetic factors that contribute to skin conditions will guide the development of new and more effective ways to prevent and treat these skin conditions, and so improve quality of life: skin health is an important aspect of longevity and wellness.
The second type of genomic application is early detection of disease, particularly cancer. The use of tests like Grail, based on detecting mutated DNA circulating in the blood, is growing fast. This is currently used to flag possible tumours at a sub-clinical level and will steadily move from screening particularly high-risk individuals to the general population, once the system learns to deal with the false positive problem (currently up to 20%) and once the tests become more specific.
Third, genomics for drug discovery. The more we understand which genes are associated with either age-related diseases or resistance to them, the greater the number of protein targets for drug R&D to tackle. Some of the most promising include sirtuins (which regulate metabolism in the face of stress), FOXO (transcription factors for stress resistance) and AMPK (which regulates energy metabolism). It’s conceivable, in the future, that anti-aging drugs might be personalised to counter the mechanisms of aging that are most prominent for an individual.
Our genome is not our destiny, as I like to say, but our management challenge. And the main management mechanism is to change which genes are expressed, under which conditions, and which not. Gene expression is controlled by our epigenetics, which in turn is influenced by diet, lifestyle and – perhaps in the future – drugs that can turn back our epigenetic clock. But the exciting developments in clocks and epigenetics will be the subject of a future newsletter.
An Invitation to My Readers
These newsletters aim to bring together the insights of a growing circle of thought leaders in the healthy longevity field. So I am reaching out to those I already know, to be interviewed on the topics they know most about. This is also an opportunity to showcase their own initiatives and contributions.
You are also invited to get in touch so that your own thoughts and enterprises feature in future newsletters, which of course you can flag to your own circle of contacts. Please get in touch to discuss your area of healthy longevity focus.
