How Much do Our Genes Control How Long We Live?

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There are many people who believe that our ability to live long, healthy is dependent on the genes we are born with. Those whose parents and grandparents have lived long, believe they will live long and those whose parents and grand-parents have died young, believe they won’t live long. Some people have a fatalistic attitude to life, believing that whatever has been ordained (a combination of genetics and fate) cannot be changed, so why bother to do anything, positive or negative, to change the course of our lives.

I first discussed genetics  on 14th Feb 2021. Monogenic abnormalities like thalassemia are inheritable diseases that afflict multiple individuals in families and those affected have to take care to ensure that the disease does not pass down the family tree.

However, when we read news reports or listen to scientists or doctors talk of genetic risk of disease, these days their focus is on clusters or combinations of genes that together affect longevity or specific disease risk. This is often called the “polygenic risk score” or PRS, which I first discussed on 25 Jul 2021. There are many studies on how PRS can predict the risk of disease in the future, including cardiovascular diseases and cancers, though the data is still not robust enough to use in daily practice.

Moreover, whether we will actually get the disease even though we carry a certain cluster of genes, is based on a complex interplay of the gene expression, and epigenetic factors including our exposome (air, noise, temperature), our physical activity levels, the food we eat and our social and cultural environment. It is estimated that genes determine, at best, between 10-30% of our longevity [1].

A recent publication by J Wang and colleagues [2] who looked at people enrolled in the Chinese Longitudinal Health Longevity Study helps us understand this issue.

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They studied people with “good” and “bad” genes and then stratified them according to “healthy” or “unhealthy” behavior and found that those with “bad longevity” genes gained up to an additional 4.35 years with a healthy lifestyle as compared to those with a non-healthy lifestyle and their risk of dying reduced to the same level as those with “good” genes and a healthy lifestyle.

What this means is that physical activity, sensible eating, good sleep, engaging in social activities and living with a purpose can mitigate the effects of a bad set of longevity genes and similarly, an unhealthy lifestyle can negate the effects of the so-called “good” genes.

All this again boils down to the fact that being fit and eating sensibly are perhaps the two most important factors that affect our healthspan and lifespan, irrespective of whether we are normal weight or so-called overweight or whether we have a good set of longevity genes or not.

Gene testing for prediction of disease with PRS scores is quite popular in many parts of the world and many commercial entities have started offering these tests, even though there is not enough data of their usefulness.

Some of them even resort to fear-mongering as one company (Lord's Biotech), advertising a genetic test for cardiac disease risk prediction, recently did in one our national dailies. Even if you have an increased risk of cardiac disease, it does not mean you will have a cardiac event in the future, just as having no genetic risk of cardiac disease, does not mean you will not land up with a heart attack at some stage. Epigenetic factors modulate risk significantly and resorting to fear-mongering as this advertisement did is just plain and simple wrong for so many reasons (e.g. they have mixed up heart failure and heart attack and these are not the same plus the test is not really validated for outcomes, etc), and I will try and discuss this in detail in the future.

At this point in time, genetic risk testing for disease is of no real use unless there is a strong family history and/or a specific clinical reason as determined by your doctor, to do the test.

What does this all mean for you and I?

Two things.

One, even if you seem to have “bad” genes because people in your family don’t live long, the good news is that you can reduce your “risk” of dying early significantly by being physically active and eating sensibly. Two, DO NOT get genetic testing done to see your risk of death or disease. At this stage, none of this helps, except in very specific disease situations, in which case your doctor will advise you to get these tests done for a specific reason.

You may want to get a whole genome sequencing done for fun, because it is available and no longer too expensive and perhaps for reasons of ancestry…it is fun to do and I have done it twice over…but risk analysis of disease based on these tests is currently not particularly validated and more importantly does not mean you will actually get that particular disease and most importantly, remember that all of this so-called risk can be modulated by your lifestyle.

Footnotes

1. Melzer D et al. The genetics of human ageing. Nat Rev Gen 2020;21:88.

2. Wang J et al. Healthy lifestyle in late-life, longevity genes, and life expectancy among older adults: a 20-year, population-based, prospective cohort study. Lancet Healthy Longev 2023;4: e535–43