A Study In Humans

Science May Have
Found A Way To
Tell How Long
You'll Live

written by E Rosalie 
Forty years ago,
a group of families from Utah enrolled in a study.* Each family had three generations starting with two to four grandparents and ending with a generation that contained four to sixteen grandchildren.
The study would follow them to the present day, noting their lifespans, health, and fertility. The families lived their lives, and that was it.
The information reveals stunning trends that may offer a reliable estimate of a person’s natural lifespan. It comes down to DNA, but not in the way one might think. The information is not available at birth—at least, not yet.
Our current understanding of aging holds that DNA accumulates changes, mutations, as we age. Over time, the changes send us on an ever-worsening downward slope where our bodies cease to work as they should. Eventually, we die.
How quickly a person collects these mutations stabilizes in young adulthood. What this study appears to show is that the speed of these DNA changes relates to a person’s natural lifespan.
If that speed is set shortly after puberty, then we should be able to estimate a potential lifespan roughly. Simply, accumulating DNA changes faster means reaching one’s natural death sooner.

Visualize your DNA as a book inherited from your parents

It tells a story—your story. The formerly crisp book grows tattered and worn over the years, but it tells the same story.
Sometimes the book collects edits—mutations—that leave the story roughly the same. So long as it contains the essential plot points, it still tells the story of you.
Not all edits are benign. Some edits make worrisome changes that require repair, but not to worry. Your book came with an inborn editor that rallies at the first sign of unauthorized changes. 
Quickly, your editor drafts a new page and glues it into the space where the rogue edit happened, restoring the story to its original text. 

Why don't we live forever, then?

This dutiful repair system works quickly, but the precise process requires time. Some edits slip past detection and become a part of the book, affecting how well your body functions. 
Edits collect in what are known as germline cells; these may be sperm or egg cells.
The mutation rate in these germline cells reliably predicted the natural lifespan for the people in this study. Those who entered puberty later and who had slower mutations lived longer on average.
A slower mutation rate also seemed to show that a woman would remain fertile longer, which also supports the idea that these mutations affect how well our body functions. The precise influences on the mutation rate remain unknown, though we know males mutate faster than females overall.
Returning to imagine the mutations as edits in a book, when your book contains so many edits that it is no longer a coherent story, the story ends.
The graph displays the rate people accumulated mutations in comparison to their lifespan, showing people who collected mutations more slowly lived longer.
 
Cawthon et al., 2020

The Birds & The Bees

People who entered puberty later collected mutations more slowly. Although mutations happen faster before puberty—cells multiply rapidly in early life, and this creates more opportunity for errors—the ability of the body to repair the damage is higher.
The surge of sex hormones ushers in an era where both the mutation and repair rate slow before settling into an average rate at which the germline cells collect changes. The study, as mentioned above, saw a threefold difference between the people with the fastest and slowest mutation rates. Other studies have seen similar variations in speed.
Women who had babies later in life lived longer but likely not because of their later-in-life babies.  Instead, the women collecting mutations more slowly remained fertile longer and could successfully bear children later. Longer lifespans for brothers and sisters of later-in-life mothers support the idea that it is their slower mutation rate and not the babies that drive the longer life.
Dividing the people in the study by sex and then, into fourths grouped from slowest to fastest mutation, the males in the slowest quarter lived six years longer than those in the fastest. The same comparison for women showed an eight-year difference. The discrepancy may not sound like much, but the time is comparable to the number of years lost by smokers or years gained through physical activity.

We must always consider a study’s shortcomings.

The first generation had reached grandparenthood at the time researchers enrolled them in the study. That meant people who had not lived long enough to become grandparents eliminated themselves from the study.
People who were infertile or who did not have children would also have been excluded as they would not have held grandparent status. The difference may or may not matter. Only more studies will tell.
Collecting the information involved some concrete information like death dates or birthdates for the last child born in a family. Still, for some aspects, the researchers relied upon memory. The grandmothers had to recall how old they were when they began puberty, for example. Families in the study were also genetically similar and living in one location. The environment has a significant impact on our physical health.
Despite these faults, what the researchers found falls in line with the current-favorite theory of aging, and the results were strikingly consistent. It has left my mind wandering—wandering toward the places where science can offer no answers.
How much will we want to know about our future, and could we meaningfully extend our lifespans? Will, we one day ask potential partners in life whether they expect an extended or shorter life? What if we find a way to slow the mutation rate dramatically? That might mean significantly increasing our lifespans.
What once were silly questions asked by children—Would you want to know how long you’ll live if you could look into a crystal ball?—have become the questions with which we may grapple someday soon.
 
References: 
* Cawthon, R.M., Meeks, H.D., Sasani, T.A. et al. Germline mutation rates in young adults predict longevity and reproductive lifespan. Sci Rep 10, 10001 (2020). https://doi.org/10.1038/s41598-020-66867-0

 

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