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Genes & Longevity

Genes could easily be argued to be the most impactful factor to our lifespan, while also playing a major role in health span (functionality during aging). In an obvious context, genes that lead to higher risk of cancer - BRCA mutations, HER positivity, KRAS, and other genes can increase the risk of shortening lifespan. In cardiovascular disease, people with familial hypercholesterolemia have much higher risk of cardiovascular death - this all being caused to a mutation in a gene. The same is true for many other conditions, like early onset Alzheimer's, Huntington’s, etc. Clearly, having these genetic anomalies has serious consequences on our ability to live a long, healthy life; however, are there genes that could do the opposite?


Well, there’s two things to be said here. One, the answer is definitely yes - there are certain genes that are related to longer life, sometimes much longer life. For example, the gene that holds the information for the protein FOXO3A is linked to exceedingly long life [1]. People who have particular mutations in this gene are associated with enjoying almost 20 years longer life than those without these mutations. This is not limited to just these genes, with some being more specific to women (FOXO1A) [1]. Either way, the point being that sometimes genes are connected with immense longevity effects. Yet, when discussing genetics, we should also consider beyond the hardwiring, looking over the firmware, as well.


Genes are the actual structures containing information for the production of these key proteins (like FOXO), but the expression/reading of this information (genes) is largely controlled by epigenetics. Epigenetics are, simply put, tags placed on genes to encourage or discourage their reading/expression, thereby promoting or repressing the production of the protein they encode. So, while not everything comes down to the hard gene, much does, even if it can be modulated by epigenetics. Unfortunately, understanding how different habits, nutrients, molecules, and so on affect epigenetic regulation of genes is in its infancy, so the majority of the information is lacking. So, we focus on the gene, itself.


It is possible, depending on the sensitivity of the test, to look at our own genome and see if we have risk or advantage - and, if interested, the mutations at the FOXO3A that are linked to much longer life are rs2764264, rs13217795, rs2802292. I’ve mentioned these mutations before, and surprisingly, I’ve had a few people write in that they have a family history of these exact mutations, and lo and behold… all their relatives lived into their 90s. I wonder if there is a connection? 🙂



Nic


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References


[1] Martins R, Lithgow GJ, Link W. Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell. 2016;15(2):196-207. doi:10.1111/acel.12427

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