Researchers extend lifespan by as much as 35 percent in mice

February 3, 2016, Mayo Clinic
Credit: martha sexton/public domain

Researchers at Mayo Clinic have shown that senescent cells - cells that no longer divide and accumulate with age - negatively impact health and shorten lifespan by as much as 35 percent in normal mice. The results, which appear today in Nature, demonstrate that clearance of senescent cells delays tumor formation, preserves tissue and organ function, and extends lifespan without observed adverse effects.

"Cellular senescence is a biological mechanism that functions as an 'emergency brake' used by to stop dividing," says Jan van Deursen, Ph.D., Chair of Biochemistry and Molecular biology at Mayo Clinic, and senior author of the paper. "While halting cell division of these cells is important for cancer prevention, it has been theorized that once the 'emergency brake' has been pulled, these cells are no longer necessary."

The immune system sweeps out the on a regular basis, but over time becomes less effective. Senescent cells produce factors that damage adjacent cells and cause chronic inflammation, which is closely associated with frailty and age-related diseases.

Mayo Clinic researchers used a transgene that allowed for the drug-induced elimination of senescent cells from normal mice. Upon administration of a compound called AP20187, removal of senescent cells delayed the formation of tumors and reduced age-related deterioration of several organs. Median lifespan of treated mice was extended by 17 to 35 percent. They also demonstrated a healthier appearance and a reduced amount of inflammation in fat, muscle and kidney tissue.

"Senescent cells that accumulate with aging are largely bad, do bad things to your organs and tissues, and therefore shorten your life but also the healthy phase of your life," says Dr. van Deursen. "And since you can eliminate the cells without negative side effects, it seems like therapies that will mimic our findings - or our genetic model that we used to eliminate the cells - like drugs or other compounds that can eliminate senescent cells would be useful for therapies against age-related disabilities or diseases or conditions."

Darren Baker, Ph.D., a molecular biologist at Mayo Clinic, and first author on the study is also optimistic about the potential implications of the study for humans.

"The advantage of targeting senescent cells is that clearance of just 60-70 percent can have significant therapeutic effects," says Dr. Baker. "If translatable, because senescent cells do not proliferate rapidly, a drug could efficiently and quickly eliminate enough of them to have profound impacts on healthspan and lifespan."

Explore further: Researchers reduce stem cell dysfunction and metabolic disease in aged mice

More information: Nature, DOI: 10.1038/nature16932

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5 comments

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betterexists
3 / 5 (2) Feb 03, 2016
Use on Pet Dogs/Cats first....Gather Data!
Bilroy
4.2 / 5 (5) Feb 03, 2016
Aren't these drugs called "Senolytics" as reported by Mayo and Scripps Research in March of 2015? The combination of Quercetin and Dasatanib (A cancer drug.) were found to increase lifespans of mice and this drug combination was reported to be a "Senolytic" agent, also by clearing dying Senescent Cells. Apparently this new discovery of the AP20187 Drug is also a Senolytic Drug and these discoveries are leading the way in the possible improvement in life and health spans in humans. Bring it on.
dedereu
3.7 / 5 (3) Feb 03, 2016
As humans, in our past from monkeys, we have already increased our lifespan, quite more than dogs or mamals of same weight and thus likely this method will not work for us as much as on mices, with very short lifes !!
What these mices eat as for humans could be as much important ??
Torbjorn_Larsson_OM
5 / 5 (1) Feb 04, 2016
As a comparison, low calorie diet was seen to extend lifespan and most important the healthy lifespan in organisms from nematodes to mice to the same extent. But that failed miserably in apes.

For one thing, despite rodents and primates being sister clades, their cell regulation is widely different (i.e. use of small RNA et cetera).

For another, what dedereu said. If this works to prolong healthy life, we have likely already evolved it. The human immune system is known to be particularly aggressive (re clearing of senescent cells). Of course, we are unlikely to have evolved every trick in the Gilgamesh myth trade, so we have to check it.

[As an aside, I am personally more interested in naked mole rats long healthy lifespan physiology. They suppress cancers better and keep skin healthier than we do.]
Torbjorn_Larsson_OM
5 / 5 (1) Feb 04, 2016
@betterexists: Certainly, I think the low calorie experiments in apes taught senescence scientists that they need to check rodent results, who already are much more related to us than Carnivora. But in apes, since we react differently from other monkeys.

@Bilroy: Yes. They then talked about checking long term effects, so that may be why they have another (likely then modified) molecule (if they have). [ http://www.scripp...ell.html ]

Here is an interesting putative mechanism:

"using transcript analysis, the researchers found that, like cancer cells, senescent cells have increased expression of "pro-survival networks" that help them resist apoptosis or programmed cell death." [Ibid]

The usual risk is be that prolonging life would increase cancer rates. This seems more entangled in that regard. Yikes. Best of luck Scripps, you will need it!

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