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Why do supercentenarians live so long?

DNA is a factor in being a supercentenarian, and CRISPR may hold the key to reversing aging
Why do supercentenarians live so long? hero image

When we are talking about older people, we have octogenarians (people in their 80s), nonagenarians (people in their 90s), and centenarians (people in their 100s). 

What is a Supercentarian and How Many are There?

And then there’s a class all to themselves: supercentenarians—people who are 110 years or older.

In all, some 1,500 people are supercentenarians. One in 1,000 people who reach the age of 100 live on to 110; several dozen are alive today, including a woman in Japan who was born on Jan. 2, 1903.

What do supercentenarians have in common to live so long?

Supercentenarians themselves cite a number of factors helping reach their amazing age, including chocolate consumption, treating their skin with olive oil, smoking cigarettes (!), and eating sushi.

But genetics of supercentplays a role, too. According to Boston University’s New England Centenarian Study, genetics plays a role in those who live into their 90s and beyond.

“This genetic influence probably involves many genetic variants with individually modest effects, but as a group, they have a strong effect,” the study’s website notes. “But for some rare exceptions, centenarians have just as many disease-associated genetic variants as the average population. Thus, their genetic advantage is likely due to variants that slow aging and decrease risk for aging-related diseases such as heart disease, stroke, cancer, diabetes and Alzheimer’s Disease.”

The ongoing study found 281 genetic markers that are 61% accurate in predicting who will make it to 100, and that are 85% accurate in predicting who lives on to 105. Those markers point to 130 genes which play roles in conditions like cancer, high blood pressure, and heart disease.

As described by The New York Times, pinning down what that genetic variant is has proven to be hugely difficult—actually, even finding people that old whose age can be verified is pretty tough, thanks to spotty record-keeping.

A 2014 study of supercentenarians went looking for a long life gene—and may have found one.

In that study, researchers performed whole exome sequencing of 17 supercentenarians, performed an annotation, filtered out common variants, and collapsed all variants into genes, from which one stood out: TSHZ3. They also found one person with a known pathogenic allele in gene DSC2, which is associated with the potentially fatal condition known as arrhythmogenic right ventricular cardiomyopathy.

“The presence of this mutation in the DNA sequence of a young person today should be reported to him/her and their families with caution, as it may or may not result in arrhythmogenic right ventricular cardiomyopathy,” researchers wrote. “Generally, variants that are annotated as pathogenic are of unknown penetrance.”

A 2008 study of extreme longevity in Japan, meanwhile, identified another variable: mitochondrial DNA haplogroup D4a—an Asian haplogroup contemporarily found in central and northeast Asia. Researchers then analyzed the data to see if the longevity was due to population structure or a property of a mutation.

“The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity,” researchers wrote. “The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.”

What is the maximum age can a human live?

According to an article in Biogerontology, the theoretical maximum age a person can currently be is 126. 

Besides DNA, longevity in humans is often tied to diets, and in particular the so-called Blue Zone diet, a set of common foods found in the areas of the world where people live the longest, including long-life hotspots like the Italian island of Sardinia.

But evolving CRISPR technologies could upend that. Recently, scientists found that Cas9 therapy can slow aging, improve health, and extend lifespans in mice. That therapy involved the injection of an adeno-associated virus with two synthetic guide RNAs and a reporter gene; the guide RNA led the Cas9 protein to a specific DNA location where it disrupted two proteins associated with early-onset dementia, lamin A and progerin.

Aging itself is a risk factor for debilitating conditions such as cancer and Alzheimer’s, noted a 2019 study, meaning that longevity alone is not a key to better living. What is needed is an actual anti-aging process, which CRISPR may be able to deliver.

In that study, published in Nature Medicine, Cas9 gene editing was found to suppress the accelerated aging usually seen in mice with Hutchinson-Gilford progeria syndrome—a rare disorder which also affects humans. An adeno-associated virus with two synthetic guide RNAs and a reporter gene was injected into study mice. Two months later, the mice were healthier, stronger, and more active, and overall, their lifespan increased about 25%.

While CRISPR is by no means yet a ticket to eternal youth, it’s being tested in the fight against Alzheimer’s and malaria, with more possibilities on the horizon. No, you’re not going to stop aging when you turn 21, but the possibility of longer lives with the help of CRISPR is being explored.

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