- A new paper investigates how the slow accumulation of certain mutations in DNA affects human life span.
- Called somatic mutations, they begin accumulating in cells from birth.
- The study shows that mutations in certain cell types, such as neurons, may be a key factor in defining a human’s maximum possible age.
- In line with the mathematical model scientists created, researchers calculated the maximum age a human could reach as up to around 190 years.
In the Bible, we learn that humans should expect to survive to the age of “three score years and ten,” or 70 years in modern parlance
Today, the internet is awash with influencers claiming that their wellness “hacks” will extend your life span well beyond the boundaries we consider typical today
However, a new study, published in the journal NPJ Aging
, might push the biblical limit back somewhat, while putting a lid on lofty influencer claims of eternal life
According to the new paper, genetic changes that occur throughout our lives create “critical longevity bottlenecks.” The authors believe this places the upper limit of human life span at around 190
The mysterious inevitability of aging
Ask anyone from any culture to explain what “aging” is, and they will be able to give you some kind of answer. However, if you ask a scientist, the answer will be long, couched in caveats, and inconclusive
Researchers are still trying to get to grips with this complex and inevitably terminal process
In 2023, a paper published in Cell
outlines 12 hallmarks of aging. They include an increased likelihood of genetic mutations as a cell divides, an inability to manage protein production and maintenance, and mitochondrial dysfunction
Some of these 12 hallmarks are theoretically reversible. For instance, one sign of biological aging is a decrease in telomere length (the protective caps at the end of DNA sequences that prevent entanglement)
Certain interventions
can prevent telomere shortening, which should, in theory, extend life span. However, as the authors of the new paper explain, “actual longevity therapies are yet to appear.”
Death by somatic mutation
Somatic mutations are changes in the genetic code of any cell in the body, except germline cells (sperm and egg). They are an inevitable part of cell division and occur throughout our bodies and lives
Sometimes, they are triggered by exposures, such as tobacco smoke or ultraviolet light, but other times, they just… happen
Some somatic mutations are not too disruptive, and the cell can continue in its slightly altered form. Others cause enough trouble within the cell that it causes cell death
The idea that somatic mutations might be involved in the aging process dates back to the late 1950s. Scientists believe that, over the course of a life span, these mutations build and build, slowly impairing cellular functions, increasing disease risk, and helping to drive the aging process
Medical News Today contacted Jeremy Clerc. He’s an assistant professor in the Division of Precision Medicine and Optimal Aging Institute at NYU Grossman School of Medicine and a scientific writer at Assisted Living Magazine
We asked Clerc, who was not involved in the study, why somatic mutations are so important in aging:
“A person in their 80s carries thousands of somatic mutations in a typical cell. The body has no mechanism for going back and correcting damage that has already been written into a cell’s genome.”
“Over decades,” he continued, “that accumulated damage degrades how well a cell does its job, and in some cases sets the stage for cancer.”
Because cells with somatic mutations occur in every tissue of the body, and each mutation can be different, they are not aeliminate every single cell with a mutation?
So, regardless of what anti-aging interventions you attempt and which hallmarks you reverse, somatic mutations will continue to wreak havoc
With this in mind, the new paper sets out to calculate “how long humans would live if we cured most aging processes except somatic mutations.”
To investigate, the scientists developed a model in which they could calculate the general rate of somatic mutations in the different tissue types of the body. This approach allowed them to “estimate the limits to human lifespan when aging is driven purely by somatic mutagenesis.”
Is immortality a pipe dream?
Using their model, the scientists calculated that, if all hallmarks of aging are taken out of the equation (including somatic mutations), the median life span would be 1,759 years, and the maximum would be 29,921 years; a ripe old age indeed
However, once somatic mutations are added back in, these advanced ages disappear, and immortality becomes even more unlikely. The authors write:
“Our results suggest that even if all hallmarks of aging were eliminated except for somatic mutations, median human life span would reach only 146–194 years — roughly twice the current 79 years.”
MNT contacted Egle Pavyde, a pharmacist by training with a PhD in regenerative medicine and stem cell research. “We know that the longest-lived person in our history was a lady who died at the age of 122,” said Pavyde, who was not involved in the study
“This means that somatic mutations are a major driver of aging but can’t account for it all by themselves,” she said
While these results might come as a disappointment to biohackers and optimizers aiming for immortality like Bryan Johnson, the scientists hope their novel approach might offer a starting point for investigating how individual biological processes contribute to aging
Potentially, it could help identify which mechanisms should be prioritized when exploring new ways to slow aging
At-risk organs for aging: Heart and brain
Interestingly, the authors found that some of the tissues in our bodies are more resilient to somatic mutations than others. In particular, liver cells. According to their models, these cells would happily replace old cells and continue to thrive for 100,000 years or more
At the other end of the spectrum, myocardial cells (from the middle layer of the heart wall) and neurons (brain cells) are much more susceptible to somatic mutations. This is because these cells are “terminally differentiated.” In other words, they no longer divide and multiply, so once their function is lost, it cannot be regenerated
Once these cell types fail, the heart and brain fail, and that, of course, will cause death. The authors refer to these cell types as “critical lifespan bottlenecks.”
What does it all mean?
Taken together, the results of this study suggest that, even if we could overturn the other hallmarks of aging, avoid chronic diseases, and live an accident-free life, somatic mutations would eventually ruin our fun
At the same time, they provide potential new targets for future scientists to aim at. If we could design a way to overturn or in some way manage somatic mutations, neurons and heart cells should be the main areas to focus on
However, we should take the results with a pinch of salt
“This study is only mathematical modeling, and not a real-life exercise,” Pavyde told MNT. “It’s a theoretical extrapolation built on simplified assumptions. It models a hypothetical human with every other aging hallmark switched off (which is not biologically achievable).”
“It also relies on estimated mutation rates and cell-death thresholds from a limited set of tissues, and doesn’t capture how the various hallmarks of aging interact and compound one another,” she added
How to fend off aging
While we wait for the key to immortality, we asked Pavyde how people can extend their lives without hi-tech interventions
“Since the paper itself implies most of what limits us today comes from aging processes other than mutations, the practical levers remain the well-evidenced basics.” According to her, this includes:
“Don’t smoke, be physically active, eat a whole-food diet, prioritize sleep, maintain strong social connections, and keep up with disease prevention at all costs. This alone can add up to 10–20 years of additional healthy years.”
“To date,” she concluded, “there are no other interventions that can provide a greater effect.”
“If human life span is constrained by non-regenerative tissues,” Clerc added, “then safeguarding the heart and brain remains our highest-value strategy. The best advice is something you’ve already heard: sleep well, eat well, move around, manage stress, and do them consistently.”
