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What makes longevity run in families? Hint: Not good genes!

Common folklore has it that longevity is in your genes. We all know people who got old and whose parents and grandparents also lived to very ripe ages. There is certainly some truth to this notion, as scientists have shown that the Alzheimer-and Cardiovascular Disease associated APOE4 allele is mostly missing in very old long-lived people, and the protective APOE2 allele is more frequent. More than 10 SNPs have reproducibly been found associated with living longer. 1

Knowing a few SNPs that influence longevity does not mean we know the heritability, how much of the population variation in longevity is due to genetic variants. Heritability usually is estimated by comparing the concordance of monozygotic (identical) twins with that of dizygotic (fraternal) twins, or between siblings and half-siblings, and parents and children. These studies show some heritability, in the order of 15-30%. Moreover, a recent study found an important flaw in the old data on heritability. This new study 1 accessed millions of people’s birth and death records in a popular ancestry research site. They merged all the many trees of millions of people, taking care to avoid double counting. Their initial analysis came up with similar estimates as the historic estimates, in the 15-30% range. But then they ran an important control: Spouses usually share no DNA but do share the same environment in terms of diet, toxins exposed to etc. What the researchers found is that spouses’ life expectancies were even more highly correlated with each other than relatives! Was spouses’ similarity due to assortative mating, people of similar phenotypes are attracted to each other, or because they shared the same home, food, and toxins? To untangle this, they looked at in-laws that don’t typically share the home such as siblings-in-law, and found correlation there too, indicating a significant factor was assortative mating, not the home environment. Assortative mating, if not properly taken into account, will exaggerate the heritability estimate; indeed, once spousal correlation was taken into account, heritability was less than 10%. This means that most of longevity is not due to genetically inherited factors, contrary to most people’s thinking. A likely major factor driving longevity, authors argue, may be socioeconomic status. Clearly, rich and educated people lived longer than poor farmers or laborers, and people usually marry within their social class. The exceptions to this rule are rare enough to become topics of novels and movies.

But isn’t that a bit disappointing? It’s the environment, and then you can’t do anything about it anyway? It’s what you got born into? Well, first, it is more encouraging than being fate of genes you can’t change! It also means now researchers should design new studies to see what exactly in the environment it is that makes people and their mates live longer. Again, contrary to what you might think it isn’t just being rich and not poor!

We can look to “blue zones”, the five areas of the world where people live longest. Remarkably, none of the long lived blue zones are in affluent areas of the world! What do we know about Sardinia (Italy), Okinawa (Japan), the most famous and well-studied areas, as well as Nicoya (Costa Rica), Icaria (Greece) and the Seventh-day Adventist community in Loma Linda, CA (USA) National Geographic recently ran an article 2 (from which the figure to the right was taken) trying to get at exactly what may contribute to longevity in three of these communities – in addition to genes. Themes that emerged from the National Geographic article are not new: Don’t smoke, don’t drink much, have a purpose in life (faith, family, work), be active every day, eat lots of vegetables, and have a good social life. Easy, isn’t it?

Literature Cited:

1. Ruby JG, Wright KM, Rand KA, Kermany A, Noto K, Curtis D, Varner N, Garrigan D, Slinkov D, Dorfman I, Granka JM, Byrnes J, Myres N, Ball C: Estimates of the Heritability of Human Longevity Are Substantially Inflated due to Assortative Mating. Genetics. 2018 Nov;210(3):1109-1124. doi: 10.1534/genetics.118.301613.
2a) Here Are the Secrets to a Long and Healthy Life: Diet is the key to longevity—but also sex, naps, wine, and good friends. https://news.nationalgeographic.com/2015/04/150412-longevity-health-blue-zones-obesity-diet-ngbooktalk/
2b) Dan Buettner: https://bluezones.com/wp-content/uploads/2015/01/Nat_Geo_LongevityF.pdf

Contributor: Margit Burmeister University of Michigan (margit@umich.edu)

Copyright Margit Burmeister, Ph.D.

Dr. Burmeister was trained in biochemistry at the Free University Berlin and the Weizmann Institute of Science in Israel and received her Ph.D. in Biology from the Ruprecht Karl’s University of Heidelberg for work at the European Molecular Biology Laboratory. After postdoctoral training at the University of California San Francisco, she became faculty at the University of Michigan. Her research has identified many genes involved in human Mendelian neurological disorders, and explored gene x environment interactions related to addictions and depression. She collaborates across Europe, Turkey and China, where she teaches regularly.

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