The key to anti-aging drugs could be taking them briefly while young

What if anti-aging drugs are most effective when taken for a short period of time when we are young? A new study speculates brief drug treatments in early adulthood could be the most effective way to extend our overall lifespan.

The new research focused on a drug called rapamycin, which was first discovered in a soil sample from Easter Island half a century ago and subsequently used as an immunosuppressive agent to help prevent organ rejection. Over the past decade a growing body of research has begun to suggest rapamycin could be an anti-aging medicine, extending lifespan in worms, fruit flies and mice.

Of course, the problem with translating these findings to humans is that chronic use of an immunosuppressive drug will cause a whole host of negative side effects, even at very low doses. So the new research, from a team at the Max Planck Institute for Biology of Ageing in Germany, wondered if any life-extending benefits of rapamycin could be gained by shorter periods of dosing at certain points in early life.

“At the doses used clinically, rapamycin can have undesirable side-effects, but for the use of the drug in the prevention of age-related decline, these need to be absent or minimal,” said lead investigator on the study, Paula Juricic. “Therefore, we wanted to find out when and how long we need to give rapamycin in order to achieve the same effects as lifelong treatment.”

The first experiments looked to a species of fruit fly commonly used in anti-aging research because its short lifespan offers good insights into the effects of any specific life-extending intervention. The striking findings revealed that giving the flies rapamycin for a short period of time in the first few days of their lives was just as effective at extending lifespan as chronic lifelong administration.

And just as significantly, the research found beginning rapamycin treatment at any other later stage of life was not as effective at extending lifespan. In particular, beginning rapamycin treatment very late in life was completely ineffective at extending lifespan.

“When the flies were treated with rapamycin in late life, on the other hand, it had no effects at all,” said study co-author Thomas Leech. “So, the rapamycin memory is activated primarily in early adulthood.”

The researchers then looked to mouse models to further explore the idea of “rapamycin memory” in mammals. Here, to measure the effects of rapamycin on aging in mice, the researchers tracked changes over time in lipopolysaccharide-binding protein (LBP) levels. This blood-based biomarker has been found to associate with age-related changes in the animals’ gut.

Over time, as mice age, LBP levels rise signaling a weakening of intestinal integrity. However, when mice are given rapamycin from the age of around three months their levels of LBP tend to stay low, indicating the drug’s potential anti-aging effects.

The big finding here was that giving the animals rapamycin just between the age of three and six months was enough to maintain low LBP levels up to the age of 12 months. In fact, at 12 months LBP levels in the animals were similar regardless of whether they had been taking rapamycin their entire life or for just a period between the age of three and six months.

According to the researchers these findings mean anti-aging drugs such as rapamycin could be more effective when administered for brief periods at younger ages. As most aging phenotypes begin to accumulate in adulthood it may be that pharmaceutically targeting this developmental window could offer the most effective long-term improvements to lifespan.

Proving this kind of speculative idea in humans though is bound to be challenging. No one is lining up for a clinical trial spanning 50 years where some kind of drug intervention in one’s younger years can be followed for decades to understand whether it extends a person’s lifespan.

Partridge said further work will try to better understand the optimal times to administer drugs like rapamycin by looking at different biomarkers related to aging in both mice and humans.

“It will be important to discover whether it is possible to achieve the geroprotective effects of rapamycin in mice and in humans with treatment starting later in life, since ideally the period of treatment should be minimized,” Partridge said. “It may be possible also to use intermittent dosing. This study has opened new doors, but also raised many new questions.”

The new study was published in the journal Nature Aging.

Source: Max Planck Institute for Biology of Ageing

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