Why you shouldn’t get too upset about claims that scientists have reversed aging… until now

Over the past few weeks, there have been some surprising claims about the science of anti-aging. Three weeks ago, a study by Rejuvenate Bio found that it increased the lifespan of mice “by 109 percent.” The following week, a second Harvard study showed that aging can be “switched back and forth at will” with new genetic techniques.

Media reports caused a stir. We’ve heard about “lifetime dose doubling” in mice and how “old mice become young again”. Several outlets spoke of an “ageing cure” on the horizon. Maybe this is finally a step towards a real, scientific Elixir of youth?

To answer this question, we need to take a closer look at what the study actually found. And it turns out that the studies are much more cautious and cause much more controversy among scientists than media reports suggest.

Both new studies used similar methods based on well-established cell biology. All of our cells have the same DNA but somehow know whether to become skin cells, brain cells, blood cells, or some other type of cell. That “somehow” is epigenetics: a set of DNA-bound biochemical mechanisms that tell the cell what its job is to turn different parts of its genome on and off.

Biologist Shinya Yamanaka received a joint Nobel Prize in 2012 for the discovery that a particular set of genes—now called “Yamanaka factors”—when specifically activated, can transform a certain type of mature cell into a stem cell—often a multifunctional one.

In a sense, this is cell aging, because cells begin life as stem cells and then develop according to their epigenetic program. It works very well in the lab, hence the Nobel Prize. But can Yamanaka factors be used to age the cells of adult living creatures – first in laboratory mice, and then, perhaps, in humans – to turn back time in their biology?

Here’s the problem: when you age cells this way, they lose their epigenetic program and identity (that is, they no longer play a specific role as a specific cell type). In the future, when they begin to grow and divide, they may turn into the wrong type of cell, which may mean turning into tumors. The risk of developing cancer as a result of this type of cellular “reprogramming” is one of the major hurdles facing scientists interested in reversing aging.

The first of the new papers, which has not yet been peer-reviewed, attempts to circumvent this hurdle by only partially reprogramming the cells. They injected laboratory mice with only three of the four Yamanaka factors and tried to rewind their cells into the Goldilocks zone, where they are younger, but not completely back to stem cells. And after that, they found that they had successfully increased the lifespan of mice—by as much as 109 percent.

This percentage can be misleading without context. All of the mice in the experiment were already old—in fact, their average mouse lifespan was nearing its end, which is about 120 weeks. So the 109 percent increase was due to their remaining lifespan, which was only a few weeks — the 20 mice treated with Yamanaka factors lived an average of 10 weeks longer than the 20 mice in the control group. Not only that, only three of the Yamanaka mice lived longer than the longest-lived control mouse. This meant that the overall statistical result was rather unreliable, relying only on a few data points, and requiring repetition on a larger sample.

When it comes to the all-important question of whether the aging process also causes cancer, the results are unclear. As physician and YouTuber scientist Brad Stanfield points out, a few weeks of extra lifespan is not enough to tell whether Yamanaka factors would pose a risk of developing cancer at a younger age. Stanfield also criticized the study report, stating that the paper was rather short and did not explain the experiment in sufficient detail to enable other laboratories to conduct these important replication studies.

The results of the second article – on the forward and backward movement of aging – are published in the journal. cell – more complex. The researchers did not directly attempt to increase the lifespan of their lab mice. Instead, they focused on the physical properties of aging and how it can be triggered and reversed with the right biological manipulations.

There are many different theories as to why animals age. The classic theory is “mutation”, which suggests that aging is due to the accumulation of small copies (mutations) and other forms of DNA damage. The other is the so-called “information” theory, which states that it is not the DNA defects themselves that cause aging, but the cellular “repair” processes that eliminate them. These repair processes are normal and important, but they violate the epigenetic instructions we discussed above – “information” cells must function properly. The theory claims that this causes the negative changes we associate with aging.

To test this idea, the researchers took a special group of genetically engineered mice and used the drug to cut their DNA without causing mutations. These DNA repair processes then came into play. Of course, there were changes in mice in their epigenetics — and as information theory predicted, these epigenetic changes were similar to those seen in old mice. They also developed physical traits closer to older mice: whiter fur; less body weight; slower movement.

The scientists then went the opposite way: they injected these prematurely aged mice with Yamanaka factors. After a few weeks, they found that their epigenetic measurements were again more similar to those of younger mice. It was epigenetic aging that they really meant when they talked about “pushing aging back and forth.”

It is important to remember that this is where the study ended. They did not show that Yamanaka-treated mice looked or behaved younger (and did not test their lifespan, unlike the first study). The study made no attempt to measure this, which may come as a surprise and disappointment to readers intrigued by the claim that aging is now completely under the control of scientists.

There is one more problem. A lot depends on whether the DNA cutting technique they used caused absolutely no mutations or other DNA damage – and some other scientists not convinced It was. Charles Brenner, a biochemist at California’s City of Hope Medical Center and a longtime critic of what he sees as exaggerated anti-aging claims, noted: I that a 2021 study by some of the same researchers found that a similar technique actually causes DNA damage and even kills cells. This old study was not mentioned or cited in the new study. At the time of publication, the researchers did not comment on when I asked in their study about possible DNA damage.

If the method inadvertently altered the DNA of cells, rather than simply affecting epigenetic aspects, then the study was not a good test of the “information theory” of aging. It also becomes unclear what the end result of the work actually means – mice returning “younger” epigenetic signals (doubly because, as we saw above, they did not check whether the mice looked or behaved younger). Brenner also notes that the signs of aging caused by DNA damage are not new, according to a 2015 study.

On closer inspection, both studies are still interesting, but much less exciting. The first considered mice of natural age, but he was small, lacking in detail, and did not study his technique long enough to be sure of its safety. The second caused artificial aging, but there are still big questions about exactly how this happened (Brenner and colleague James Timmons of Queen Mary University of London are planning to write a critique of the second edition so we can discuss it in order to continue). . .

Not surprisingly, anti-aging research is prone to hype and wishful thinking: not only does a scientist who has cured aging bring huge benefits in the form of fame and fortune, but the ability to hold back years and live longer healthy lives, which almost everyone wants. every. do. .

These incentives do not sit well with the sheer complexity of the new biochemical studies of aging. With their clutter of graphs, images, and statistics, studies are difficult to read even for experts and reviewers, and anyone who describes them, including scientists, is tempted to obfuscate the details with simpler claims that “it reverses aging.” . “.

But the scientific debate surrounding these two studies reminds us to look beyond simple, exciting headline claims. It’s good to be frank, but the details matter.