Overview of Dr. Andrew Steele’s top five most promising anti-aging compounds:
1. Rapamycin extends mouse lifespan by approximately 10%, while a similar drug — RTB101 — is linked to enhanced immunity in older adults according to clinical data.
2. Senolytics, which target and reduce aged, dysfunctional cells, can extend a mouse’s lifespan by several months, equating to a few years in humans.
3. Metformin, widely used for diabetes management, is associated with a lifespan extension of a few months in diabetic patients compared to untreated adults without diabetes, somewhat countering the usual life-shortening impact of diabetes.
4. Taurine, a sulfur-containing protein building block (amino acid) that supports nerve growth, declines in our bodies with age, and supplementation can extend mouse lifespan by 10%.
5. Statins, cholesterol-lowering drugs, are linked to decreased risks of heart disease and overall reduced mortality in humans.
Dr. Andrew Steele has an interesting occupational background, beginning with a physics PhD from Oxford University and progressing to computational biology and aging research. With his current aging research, Steele has compiled a list of what he believes are the top five most promising anti-aging drugs to date, all reviewed in a YouTube segment.
“Did you know that there are drugs that can slow down the aging process?” asks Steele.
Rapamycin Extends Mouse Lifespan and May Improve Immunity in Aged Adults
Originally discovered on the island of Rapa Nui (Easter Island), rapamycin has steadily gained medicinal popularity. In the clinic, rapamycin is used to help transplant patients avoid tissue rejection; as a coating for tiny metal or fabric tube-like devices used to open blocked or narrowed blood vessels (stents); and as a cancer treatment. However, further excitement began to build in 2009 when scientists found that it extends mouse lifespan by about 10%.
Furthermore, human data from 652 participants showed that usage of a similar drug, RTB101, is associated with improved immunity in older adults. What’s more, the same study found that serious side effects from this treatment were rare. Along those lines, the evidence we have from studies of rapamycin are mostly positive, showing safety and potential anti-aging benefits.
However, according to Steele, we do not yet have the evidence to conclude rapamycin is an effective anti-aging drug. He says we need a larger human trial comparing those who take rapamycin to those who do not to tell whether rapamycin improves general health in older people. Steele suggests that we wait for more conclusive human trial results from an ideal rapamycin study before making a decision about potential health benefits.
Senolytics Remove Aged, Dysfunctional Cells that Emit Toxic Molecules to Extend Mouse Lifespan
As we age, senescent cells accumulate in tissues throughout our bodies. Senescent cells are aged, dysfunctional cells that emit a toxic cocktail of inflammatory molecules, and their buildup can accelerate the aging process. Interestingly, senolytic compounds like dasatinib, a chemotherapy drug, and quercetin, a flavonol molecule found in fruits and vegetables, can be used to eliminate them. This positions senolytics as one of the hottest potential anti-aging drugs, according to Steele.
In a 2018 study, scientists explored the effects of combining dasatinib and quercetin, on mice approximately equivalent to 69 human years old. Interestingly, the mice lived a few months longer, the equivalent of a few years in humans. Most importantly, the mice given senolytics stayed healthier with delayed onset of diseases like cancer. Furthermore, the mice could run further and faster, a mouse version of delayed frailty. What’s more, the mice that received senolytics looked much healthier than mice not treated with senolytics. These results provide preliminary evidence for the anti-aging benefits of the senolytics dasatinib and quercetin. Because of these preliminary studies, Steele says that this class of anti-aging drugs may be worth getting a little excited about.
Metformin May Make People with Diabetes Live Longer
Steel’s third most promising anti-aging drug is the diabetes medication and possible longevity pill metformin. According to a few data sources, though, metformin may do more than keep people’s blood sugar in check.
A study examining UK medical records showed that metformin usage was associated with extending diabetic patients’ lifespan by a few months. This is important since those with diabetes have many other health problems leading to reduced expected survival.
Because of these lifespan records from the UK, the question became whether metformin helps with other age-related problems like cancer. To address this question, researchers designed a randomized human trial called TAME (Targeting Aging with Metformin) with hopes of enlisting 3,000 healthy older adults. Researchers conducting the study planned to randomly give metformin to half of the study’s participants with the goal of finding whether those who take metformin live longer. Frustratingly, the TAME trial has been ready to go for a few years, but researchers cannot acquire the funding necessary to carry it out. Hopefully, the TAME study will eventually acquire the funding to execute it for the first ever trial of a drug against aging itself.
Taurine Levels Fall with Age, and Counteracting This Decline with Supplementation May Enhance Longevity
Another potential anti-aging drug that Steele says he is bullish about is taurine. This sulfur-containing amino acid is found in numerous energy drinks, and a 2023 study showed that its supplementation slows aging in mice and monkeys. In addition to these findings, researchers showed that taurine extended mouse lifespan by about 10%. What’s more, after giving taurine to monkeys, scientists found that the monkeys were healthier. However, it will be a few more years before researchers find whether taurine-supplemented monkeys live longer, similar to mice.
The taurine study represents over a decade of work, and the paper has 56 authors. Due to all of the work that needs to be done to test taurine, Steele is hopeful some group of scientists will “take the bull by the horns” to run a human trial and see whether this amino acid slows human aging.
Statins Reduce Cholesterol and Heart Disease Risk and Are Associated with Lower All-Cause Mortality
Statins are widely prescribed drugs used to reduce blood cholesterol levels and prevent problems like heart attacks and strokes. Steele believes that they could also be used as anti-aging drugs.
The first reason for Steele’s assertion is that the normal cholesterol-lowering function of statins could be described as having anti-aging properties. Along those lines, as we grow older, we all accumulate fatty deposits in our blood vessel walls, a process that Steele says probably starts before we are even born. While many think of plaque-ridden arteries and heart attacks as something that happens in aged people, scientists studying disease processes have found early stages of cardiovascular disease from these fatty deposits in the blood vessels of teenagers. Although most teenagers and even people in their 50s will not have accumulated enough blood vessel plaques to trigger heart complications, eventually, these buildups can get so big that they cause problems leading to death.
As for mortality risk, about a third of deaths in both wealthy countries and globally stem from atherosclerotic plaque accumulation. This makes the accumulation of these fatty deposits a cumulative process that may be a contributor to aging, according to Steele. Thus, statins, by reducing cholesterol levels, may slow down aging itself in this way.
The second reason Steele believes statins may serve as anti-aging drugs is that they may have other anti-aging effects. For example, getting older entails immune cells called neutrophils losing their capabilities to navigate toward particles like bacteria, viruses, and debris (pathogens) that are foreign to the body. Instead of migrating toward pathogens, they travel random paths, causing cellular damage in their wake that may accelerate aging. Intriguingly, Steele says researchers have found that statins can restore neutrophils’ sense of direction.
Furthermore, statins may extend the length of protective caps at the ends of our chromosomes called telomeres, according to Steele. Telomeres shorten with each cell division so that they get progressively shorter with age, leading some researchers to posit telomere shortening as an aging contributor. By extending telomere length, statins may alleviate this possible process of aging.
Steele also highlights a systematic review of 54 statins associating their usage with a reduced risk of death from any cause by about 25%. He goes on to say that the associated lower all-cause mortality from statins could correspond to a few extra healthy years of life. According to Steele, while the associated reduced risk of death from any cause may be linked to a reduction in the risk of heart disease, we need future studies to help determine whether statins have a more general anti-aging effect.
The First Anti-Aging Therapeutics May Be with Us Already
Someone interested in longevity drugs may be wondering whether it is time to start popping anti-aging pills. According to Steele, unless a doctor advises you to take one of these pills for a specific condition, it is probably best to watch and wait. While some of these drugs may work in the laboratory for cells in a dish or in animal models like mice, we still need more human trials to determine their safety and efficacy for human use.
There are literally hundreds of potential anti-aging drugs under investigation, so Steele suggests criteria to identify which ones have the most potential. The first of these criteria entails finding whether it works in extending mouse lifespan. Along these lines, the Interventions Testing Program rigorously tests whether new drugs under investigation increase lifespan in mice. If there is no data pertaining to mouse lifespan, another thing to look for is whether there are positive data for anti-aging effects in other organisms like flies, worms, and yeast. The last criteria is whether there are any indirect human results, such as a reduced risk of mortality, associated with taking a drug. A pitfall to using human data is that most of these studies assess the effects of drugs using participants who already have a condition, like cardiovascular disease, which increases the risk of mortality.
Applying these criteria may help one to pinpoint anti-aging drugs of interest and keep tabs on the drugs’ ongoing research. Future promising results may develop for some of these therapeutics, and if this is the case, perhaps one day, we will all have safe and effective anti-aging drugs for use. However, since human trials can extend over the course of decades, it may be some time before this happens.
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