Life Span Increased in Aging Mice

Medicine is continuing to make promising inroads in the area of regenerative medicine. With most developed countries facing increasingly aging populations, there’s widespread concern about mounting healthcare and social security costs.

Furthermore, attention is focusing on ensuring that lives are not only long but also fruitful. Perhaps the greatest hardship of growing old isn’t facing death, but enduring a painful and extended process of physical and mental decline, which furthermore puts an emotional and financial burden on loved ones.
Therefore, any practical and ethical means of at least mitigating our inevitable deterioration should be welcomed. The quantity of life means far less without the quality – hence my excitement over a study reported in National Geographic that managed to biologically rejuvenate mice on the verge of death, not only extending their lives but making them function as if they were younger.
The study mice were genetically engineered to have a condition similar to a rare human syndrome called progeria, in which children age quickly and die young. (Learn more about the human body.) The fast-aging mice typically die around 21 days after birth, far short of a normal mouse’s two-year life span.
When scientists looked at the muscle stem cells of the fast-aging mice, they found what Huard called “tired” stem cells, which don’t divide as quickly.
The team then examined mice that had aged normally and found their stem cells were similarly defective.
Curious if these deficient stem cells contribute to aging, Huard and colleagues injected stem cells from young, healthy mice into the fast-aging mice about four days before the older animals were expected to die.
To Huard’s astonishment, the treated mice lived an average of 71 days—50 more than expected, and the equivalent of an 80-year-old human living to be 200, he said.
Not only did the animals live longer, they also seemed healthier, the scientists found.
Despite all the controversy, not to mention the legal and political obstacles (at least here in the US), stem cells continue to yield remarkable results for regenerative medicine, if not medicine as a whole. It is no wonder that many scientists regard stem cell research as one of the most important avenues for improving human health. With more time, money, and societal support, they could have considerable impact on improving the quality of life for millions.
Anyway, the implications of this study become more interesting. Like all good scientists, the team undertook repeated experiments to ensure that the first results weren’t fluke, reaching the same outcome in every instance. This raised the vital question as to how the stem cells were having such dramatic effect.
To find out, the team “tagged” stem cells injected into the fast-aging mice with a genetic marker that tracked where the cells went inside the body. Surprisingly, the team found only a few stem cells in the mouse organs, squashing a theory that the introduced cells were repairing organ tissues.
The scientists went back to the lab to test another idea: that stem cells secrete some kind of mysterious anti-aging substance.
The team put stem cells from the fast-aging mice on one side of a flask and stem cells from normal, young mice on the other side. The two sides were separated by a membrane that prevented the cells from touching.
Within days, the aging stem cells began acting “younger”—in other words, they began dividing more quickly.
“We can conclude that probably normal stem cells secrete something we don’t know that seems to improve the defects in those aging stem cells,” Huard said.
“If we can identify that, we have found an anti-aging protein that is going to be important” for people, said Huard, whose study appeared January 3 in the journal Nature Communications.
There is still a lot to learn about stem cells, and it seems we’ve only begun to scratch the surface of their potential benefits. As always, there are important caveats to keep in mind before we get too excited and begin to expect age-reversing medicine on the market.
But other scientists are cautious about how soon the discovery may help people delay the aging process or treat age-related disease.
“They did a beautiful job of showing that, when they put the muscle stem cells in [the mice], they improved function,” said Justin Lathia, an assistant professor of cell biology at the Cleveland Clinic’s Lerner Research Institute.
But as far as people go, it’s still not clear what exactly stem cells do in the body, as well as what the mysterious stem cell secretion really is, Lathia emphasized.
Jeremy Rich, chair of the department of Stem Cell Biology and Regenerative Medicine at the Cleveland Clinic, also pointed out that the study is limited to muscle stem cells. That means the research can’t be generalized to include all stem cell types, which are often very different from each other.
Paul Frenette, a stem cell and aging expert at the Albert Einstein College of Medicine in New York, called the research “intriguing,” but said one of the messages for “patients is not to get too excited.”
“You see all these clinics that are popping up all over the world—even in New York—where they’re injecting stem cells” into people to treat disease, even though such therapies have not been proven.
“I don’t think people should run to the clinic right now to have injections of stem cells to live longer.”
Indeed, the news media and general public have a tendency to become overly enthusiastic or supportive of research that is still preliminary or incomplete. In our understandable anticipation of what ground-breaking benefits may emerge, we forget that scientific progress is a cautious, methodical, and arduous journey through a gauntlet of peer review, repeated experimentation, and – in the case of medicine – numerous clinical trials.
At the same time, I’ve noticed a pushback against this sentiment from the other direction, in which the response to scientific developments is too cynical or reflexively skeptical. This too is an understandable position, given the sad history of false positives, fraudulence, and exaggerations. It certainly doesn’t help that in age of information overload, we frequently encounter conflicting claims and counter-claims that it can make it difficult for us to make up our minds.
Without getting too off topic, I think the key is to maintain a balance between informed incredulity and hope – look at multiple studies, preferably from scientific journals and reputable institutions, and maintain some restraint until more time and scrutiny have passed. I’m obviously very eager about the latency of this finding, but I’m not looking forward to popping anti-aging pills anytime soon.
Science isn’t perfect, given human nature, but it has as good a track record as any of our endeavors when it comes to fact-checking. There’s a lot of work to be done.
Indeed, study co-author Huard noted that before any human anti-aging trials can begin, scientists need to repeat the experiment in normally aging mice to show whether these mice also live longer.
If that turns out to be true, Huard could imagine a scenario in which some of a person’s stem cells are harvested at about age 20 and then injected back into his or her body at around age 50 or 55.
Stem cell therapies do already exist for conditions such as incontinence and heart problems, so he thinks “we’re not that far [from applying] this approach clinically down the road.”
But Huard warned that such a treatment would not mean a 55-year-old will suddenly look and feel 25 again.
“The goal of doing this research is not to [be like a] movie star with a ton of money [who wants to] look great for the rest of their lives,” he said.
“The goal is, if you delay aging, maybe you can delay Alzheimer’s or cardiovascular problems.”
In other words, he said, such stem cell treatments would help people “age well.”
My thoughts exactly. We’ve made incredible strides in bettering the human condition, doubling or even tripling human life expectancy while – perhaps most crucially – changing the way aging effects people. Older people are becoming unprecedentedly fitter, and it’s no longer unusual to see people running for public office or joining the workforce in their sixties or even early seventies.
With the median age in most societies getting higher, even within developing countries, it’s vital to both individual and collective well-being to ensure that the majority of older people can continue to function well into advanced age. The social, economic, and ethical gains would be tremendous.

Signs of Aging Stopped in Mice

Scientists in the Mayo Clinic have managed to reduce or even completely eliminate the pathology of aging, including wrinkles, cataracts, and muscle atrophy. From the BBC article:

Scientists at the Mayo Clinic, in the US, devised a way to kill all senescent cells in genetically engineered mice.

The animals would age far more quickly than normal, and when they were given a drug, the senescent cells would die.

The researchers looked at three symptoms of old age: formation of cataracts in the eye; the wasting away of muscle tissue; and the loss of fat deposits under the skin, which keep it smooth.

Researchers said the onset of these symptoms was “dramatically delayed” when the animals were treated with the drug.

When it was given after the mice had been allowed to age, there was an improvement in muscle function.

One of the researchers, Dr James Kirkland, said: “I’ve never seen anything quite like it.”

His colleague Dr Jan van Deursen told the BBC: “We were very surprised by the very profound effect. I really think this is very significant.”

The treatment had no effect on lifespan, but that may be due to the type of genetically engineered mouse used.

Senescent cells are those which have stopped dividing. While they help prevent tumors from progressing, and often get cleared out by the immune system, they inevitably build up overtime, contributing to the symptoms of aging. Removing these cells doesn’t stop the actual biological process of aging itself – this isn’t the key to immortality – but they do improve the quality of life at old age, and that is arguably just as important.

This study brings us closer to figuring out the other side of the coin when it comes to increasing longevity – living a long life is one thing, but ensuring that life is worth living in the first place is a whole other matter. Suffering from all manner of debilitating effects – senility, muscle weakness, impaired senses – can make the advantages of a longer lifespan on this Earth moot.

Of course, like good scientists, the researchers are cautioning that this shouldn’t be taken as a done deal. The experiment was just a preliminary one, and was done only with mice – we’re not yet able to simply purge these senescent cells from our own bodies.

But it opens up the prospect of doing so, or at least helping the process along. We can try to devise a drug that stops these cells directly for example. One of the scientists involved noted that younger people are already at the point that their immune systems mostly clean these “aging” cells out – so boosting or priming immunity in some way may preempt the effects of growing old, changing forever the way we view aging or how we define “being old” (which is already being shifted through advances in nutrition and medicine).

Very exciting prospects indeed. If anyone else is interested, check out the original published work in Nature.