Rapamycin may help extend lifespan but human trials a long way off.
- Research is ongoing about
potential strategies to prolong life.
- A meta-analysis found that the
drug rapamycin prolongs life in several vertebrate species.
- Rapamycin appeared to prolong
life at a level similar to dietary restrictions.
How to
prolong life is a key area of scientific research. Experts are interested in
medications that have the potential to boost longevity.
A recent
meta-analysis published in
The
results confirmed that dietary restriction appears to prolong life and that
rapamycin offers similar benefits.
Researchers
also found that metformin did not seem to prolong life. More research is
required to see how rapamycin might help boost longevity in people.
Rapamycin:
Does it increase lifespan?
In this paper,
researchers note that decreasing food intake without malnourishment appears to
prolong life but that this strategy is difficult for people to stick to. Thus,
looking into possible medications that produce similar effects is an area of
research.
The two
medications that were the focus of this analysis were rapamycin and metformin.
According to the National Cancer Institute,
This
analysis involved a systematic literature search to find relevant data. The
final analysis included data from 167 papers looking at eight total vertebrate
species, seeking to see how both medications affected longevity and how they
compared to dietary restrictions.
Researchers
extracted information on average and median lifespan from the papers.
For this
analysis, the two types of dietary restriction were caloric reduction and
fasting, and researchers also sought to see if the results differed based on the
sex of the animals involved.
The data
came from animals like mice, rats, turquoise killifish, and rhesus macaques.
Overall, there were more males studied than females. There was also the most
data on dietary restriction, and the most common type of dietary restriction
was decreasing the number of calories.
Regarding
dietary restriction, the findings suggested great variation regarding the
effects.
Overall,
researchers found that dietary restriction and rapamycin had a similar impact
and appeared to contribute to prolonged life. Metformin appeared to only have a
minimal impact on life extension.
Aside from
one metformin model, there appeared to be no consistent differences between
male and female animals regarding longevity.
Study
author Zahida Sultanova, PhD, a Leverhulme Early
Career Research Fellow with the University of East Anglia, in the United
Kingdom summarized the key findings of the study to Medical News Today:
“We
checked whether the two best-known ‘diet-mimic’ drugs increase lifespan similar
to eating less in animals. By pooling data from 167 studies, we found that
rapamycin is almost as reliable as eating less for increasing lifespan, whereas
metformin is not. In other words, a compound that was extracted from soil
bacteria 50 years ago seems able to copy many of the biological effects of a
permanent diet, at least in lab animals.”
Do the same
benefits apply to people?
This research
analyzed animal data but did not include data about people. Additionally, most
of these studies involved these animals in a laboratory setting and only looked
at a small number of species.
This
meta-analysis was also the work of only three researchers, sometimes with only
one researcher doing a component of the work, which could have impacted the
results.
Researchers
had the least amount of data on metformin, so more research about this
medication might be helpful.
They also
operated under the assumption that if a paper did not specify male or female
subjects, it was a mixed group, which could have been incorrect.
The
authors further note that the “results were sensitive to how lifespan was
reported.”
Researchers
also acknowledge strong publication bias and a lot of heterogeneity.
Additionally, the type of measure used in study reporting affected results. In
one measurement, the impact on life extension disappeared for rapamycin.
For the
most part, the authors did not find a consistent difference in results based on
the sex of the animals. They explain this could be because of “differences in
taxonomic groups studied […] and the calculated effect size.”
Sultanova
noted the following cautions regarding the findings:
“This
study includes a high number of scientific studies conducted on different
organisms such as mice, fish and monkeys. However, survival results in humans
are not included because these drugs were not tested in humans for lifespan
extension. Even if they are, the studies will take a long time considering the
length of human lifespan. So, we do not recommend people to take rapamycin
before the results of human trials consistently show that there are no side
effects.”
Why is it hard to study rapamycin in humans?
Researchers
suggest the need for research involving other species in natural and laboratory
settings. They also note the need to understand the difference in impact for
“different strains of the same species exposed to the same treatment.”
Future
research can further focus on the differences between rapamycin and metformin
and why they impact lifespan differently. More research into the differences in
rapamycin’s results in males and females could be helpful as well.
More
research can be done to see if rapamycin can promote prolonged life in people,
but there may be some challenges in this area.
Mir Ali, MD, a board-certified general surgeon,
bariatric surgeon, and medical director of MemorialCare Surgical Weight Loss
Center at Orange Coast Medical Center in Fountain Valley, CA, who was not
involved in the study, told MNT that it “shows the contribution of the
immune system to lifespan, as rapamycin is an immunosuppressive medication.“
According
to him: “The most logical next step is to explore the findings in humans;
however, this would be a difficult study to design as rapamycin is a medication
used in specific cancers and organ transplant and has significant side
effects.”
Despite
this, the results show a potential benefit of rapamycin that warrants more
research.
Sultanova
explained that: “Clinically, that puts rapamycin (and the mTOR pathway it
targets) at the front of the queue for future anti-ageing therapies in humans.
The compound had already been used for organ-transplant patients, so medical
professionals understand its potential side effects.“
“The next
step is waiting for the results of ongoing human trials that test lower and
intermittent doses of rapamycin and refining the compound to ‘rapalog’ versions
that keep the benefits while omitting side-effects such as immune suppression,“
she told us.
“Another
important next step would be developing drugs that are similar in structure and
function to rapamycin but without the side-effects. Scientists have already
started refining rapamycin and producing the so-called rapalogs,” Sultanova
noted.
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