Slowing the aging process—only with antibiotics

Johan Auwerx, Nestlé Chair in metabolism at EPFL, head of the Laboratory of Integrative Systems Physiology (LISP), identified a group of genes whose expression have an essential impact on longevity. Credit: EPFL / Alain Herzog

Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.

Why is it that within a homogeneous population of the same species, some individuals live three times as long as others? This question has stumped scientists for centuries.

Now, EPFL researchers led by Johan Auwerx report in the journal Nature how a mechanism in mice plays a determining role in longevity. And they go a step further: by disrupting this mechanism using simple antibiotics in a population of nematodes, or roundworms, they can multiply by a factor of 1.6.

Mitochondia: biological timekeepers

The process identified by EPFL scientists takes place within organelles called mitochondria, known as the cellular powerhouses because they transform into proteins including adenosine triphosphate (ATP), used by muscles as energy.

But that's not all they do. Several studies have shown that mitochondria are also involved in aging. The new EPFL research, done in collaboration with partners in the Netherlands and the US, pinpoints the exact involved and measures the consequences to longevity when the amount of protein they encode for is varied: less protein, longer life.

Natural variations in mice

in the BXD reference population typically live from 365 to 900 days. This population, which reflects genetic variations that occur naturally within a species, is used by many researchers in an approach known as "real-world genetics." The benefit of working with this population in particular is that their is almost completely decoded.

The team led by professor Auwerx, head of EPFL's Laboratory of Integrative and Systemic Physiology, analyzed mice genomes as a function of longevity and found a group of three genes situated on chromosome number two that, up to this point, had not been suspected of playing any role in aging. But the numbers didn't lie: a 50 percent reduction in the expression of these genes—and therefore a reduction in the proteins they code for—increased mouse by about 250 days.

This video is not supported by your browser at this time.
EPFL scientists have revealed the mechanism, hidden deep within cell mitochondria, that is responsible for making organisms age. Nematodes treated with antibiotics designed to disrupt this mechanism lived longer and healthier lives. Credit: EPFLnews

Extending life in worms

Next, the team reproduced the protein variations in a species of , Caenorhabidtis elegans. "By reducing the production of these proteins during the worms' growth phase, we significantly increased their longevity," says Auwerx.

The average life span of a worm manipulated in this way went from 19 to more than 30 days, an increase of 60 percent. The scientists then conducted tests to isolate the common property and determined that the presence of mitochondrial ribosomal proteins (MRPs) is inversely proportional to longevity.

Life-prolonging stress

The researchers concluded that a lack of MRP at certain key moments in development created a specific stress reaction known as an "unfolded protein response" within the mitochondria. "The strength of this response was found to be directly proportional to the life span," says Auwerx. "However, we noted that it was more pronounced if the protein imbalance—the reduction in MRP— occurred at a young age. A similar stimulation in an adult did not affect the worms' longevity."

What's more, the effect can be induced without genetically manipulating the worms. "Exposure to certain readily available drugs inhibits ribosomal function and thus causes the desired reaction," says Auwerx. In other words, mitochondria are sensitive to certain antibiotics, and the drugs can be used to prolong life.

Weary youngsters, vigorous old folks

Worms given antibiotics don't just live to ripe old age. At maturity, which is 13 days, they also moved twice as much as the others, according to Laurent Mouchiroud, co-author of the study. "Around 20 days of age, the difference was even more pronounced because the 'control' individuals were often already in bad shape," he adds.

Using a software program modified by colleagues in EPFL's School of Computer and Communications Sciences, Mouchiroud was able to follow, measure and qualify the movements of many worms during their entire life, and he observed that those who had undergone drug treatment had superior endurance and energy. "In addition, their muscles were in better shape," he reports.

However, individuals who were given the antibiotics early in life—for example in the larval stage—also presented several less favorable characteristics. Their development was slightly slower, they laid fewer eggs and they had less energy at about three days old, the outset of adult development. "This reminded us of the vaguely flu-like state one gets right after the administration of a vaccine," says Monchiroud. "But the stress reaction in the , and thus the potential for increased longevity, remained after the treatment phase."

All indications are that the observed and proven mechanisms in worms should be similar to those in mice, and therefore possibly in other mammals. Further studies are necessary, of course, to confirm that aging and its deleterious effects could be slowed down in mammals using antibiotics at precise moments in development.

"This research gives us hope not only for increasing , but also for lengthening the period of adult vitality, and doing this with simple drugs such as ," concludes Auwerx.

More information: Paper: dx.doi.org/10.1038/nature12188

Related Stories

Worm research may help humans live longer

Mar 29, 2013

(Phys.org) —Look what might help us live longer—worms! Researchers at the Boyce Thompson Institute for Plant Research (BTI) and Cornell have shown that roundworms can live up to 20 percent longer when ...

Tweaking a gene makes muscles twice as strong

Nov 10, 2011

A team of researchers at EPFL, the University of Lausanne and the Salk Institute created super strong, marathon mice and nematodes by reducing the function of a natural inhibitor, suggesting treatments for ...

The Secrets of Longevity

Jul 15, 2010

(PhysOrg.com) -- A complex network of genes, in combination with a low-calorie diet and exercise, appears to be a key factor in a long life expectancy. Professor Johan Auwerx’s team has published an article ...

Recommended for you

Researchers try to make sure herpes does not find a home

15 minutes ago

The immune system is great at making sure infections such as the herpes virus do not repeatedly infect a person, a condition known as a superinfection. Yet how the immune system combats superinfection is ...

A new way to diagnose malaria, using magnetic fields

18 hours ago

Over the past several decades, malaria diagnosis has changed very little. After taking a blood sample from a patient, a technician smears the blood across a glass slide, stains it with a special dye, and ...

How Alzheimer's peptides shut down cellular powerhouses

Aug 29, 2014

The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

gmurphy
5 / 5 (1) May 23, 2013
Wow, science is slowly but surely getting a grip on ageing.
heatherscoggins
5 / 5 (1) May 23, 2013
Sounds like something the younger generations could benefit from. Especially since it sounds like they would only be helpful during certain stages of life.