Rejuvenation

What Are Telomerase Activating Drugs, And Should You Take Them?

Posted on 24 October 2022

Many people have heard of telomeres, the protective caps on the ends of our chromosomes. They are best known for their apparent role in the ageing process – as we grow older, our chromosomes become shorter, eventually rendering our cells unable to divide. Telomere shortening is long hypothesised to be one of the driving forces behind the ageing process. Today, it’s possible to buy dietary supplements that can extend telomere length with the aim of delaying the ageing process. What is the evidence that such products work as claimed, and are there any risks to taking them?

What Are Telomeres And What Role Do They Play In Ageing?

Capping the ends of each chromosome are the telomeres, long strands of repetitive ‘nonsense’ DNA (they don’t contain any meaningful genetic information). Telomeres have several functions. They protect the ends of the chromosomes against damage and entanglement – you can think of them like the caps on the ends of shoelaces. Telomeres also serve the essential role of protecting the genetic code during cell division. When a cell divides, each chromosome must be replicated in its entirety, but the cell’s replication machinery is unable to copy the entire length of the DNA strand – a small section is lost from the end of the strand each time it is copied. Were it not for the telomeres, this would cause important genetic information to be lost each time a cell divided.

How does the DNA sequence change with distance from the telomere? | Socratic
Structure of a chromosome and its telomeres.
Source

Once its telomeres become too short, a chromosome can no longer be replicated safely, and so the cell will become unable to divide. This might sound like a bad thing, but this actually acts as an effective safeguard against cancer. Since cancer cells divide very rapidly, they will quickly exhaust their telomeres and lose the ability to divide unless they can acquire a mutation that rebuilds their telomeres.

Unfortunately, all this comes at a heavy cost. As we grow older, an increasing number of our cells lose the ability to divide as their telomeres shorten. These cells, known as senescent cells, appear to play an important role in most age-related disease and deterioration, from muscle wasting to heart disease. Studies have also observed that species in which telomere shortening proceeds faster generally live shorter average lifespans. This leads to the idea that human ageing could be slowed by slowing telomere shortening, which is where an enzyme called telomerase enters the picture.

DNA testing companies offer telomere testing – but what does it tell you  about aging and disease risk?
Telomere shortening during cell division.
Source

What Is Telomerase And What Are Telomerase-Activating Drugs?

If our cells didn’t have a way of restoring the length of their telomeres, we would all be born with shortened telomeres inherited from our patents. Telomerase is an enzyme that adds new ‘genetic letters’ to the ends of existing telomeres in order to extend them, slowing or completely reversing their degradation. Cells that divide a lot such as stem cells, sperm cells and some immune cells produce high levels of telomerase, but the vast majority of cells in the body do not.

Some compounds have the ability to increase the activity of genes that code for components of the telomerase enzyme, thereby extending the length of the telomeres. Many are hopeful that these telomerase activators will be able to slow ageing and delay the onset of age-related diseases in humans. Cycloastragenol is one such compound, isolated from various legumes of the Astragalus genus. Another is resveratrol, which is produced by various plants. Both compounds are commercially available in various forms – if you so desired, you could start taking a telomere-lengthening drug today, and potentially age more slowly as a result. But is there any evidence that these compounds actually slow ageing? What about the risks?

Have Any Scientific Studies Shown That These Drugs Can Slow Down The Ageing Process?

Before we proceed, it’s important to take note that the relationship between telomere length and the ageing process isn’t as straightforward as you might think. One might logically assume that having longer telomeres would be associated with reduced risk of age-related diseases and increased lifespan, but this isn’t always the case. Mice have longer telomeres than humans, but obviously don’t live nearly as long. Humans that have hereditary long telomeres have reduced frequency of some diseases, but increased frequency of others, particularly cancer (though they still seem to live longer on average). All this is probably an indication that the rate at which our telomeres shorten is more important than their actual length. It shows that we can’t make assumptions about the effects of telomerase activators based on what we think we know about telomeres and ageing – we need clinical evidence.

figure5

This table shows the risk of various diseases associated with hereditary increased telomere length, in comparison to someone with average telomere length. Marks to the right of the central line indicate higher risk.
Source

So, what does the evidence say? Animal studies of treatments to increase telomerase activity have generally had promising results. When scientists used gene therapy to increase telomerase expression in mice, they found remarkable health benefits including improved blood sugar control, bone health, and muscle function. The mice lived 24% longer on average when the therapy was given at 1 year of age, and 13% longer at 2 years of age. Moreover, these mice didn’t suffer an increased risk of cancer.

Animal studies of the aforementioned telomerase activator cycloastragenol (the most well-studied natural telomerase activator) suggest that this compound can have a variety of health benefits including improved skin health, faster wound healing, reduced unwanted fat deposition, reduced inflammation, and even reduced depression-like symptoms. However, despite demonstrably lengthening telomeres, cycloastragenol doesn’t seem to extend the average lifespan of mice. Resveratrol lengthens telomeres in mice and appears to have a variety of health benefits. Another telomerase activator, AGS-499, was found to have neuroprotective effects in mice.

A. lentiginosus, one of over 3000 species of the Astralgus genus from which cycloastragenol can be extracted.
By Ciar – Own work, Public Domain

As for the human evidence, much more work is needed, but there are reasons to be excited about the potential of telomerase activators. Small clinical trials suggest that cycloastragenol can improve blood pressure, blood glucose, cholesterol level and bone density. It may also restore the immune system to a more youthful state. Resveratrol has also been found to have a variety of benefits in humans, though it’s unclear how many of these are related to telomere elongation.

When it comes to lifespan, we don’t yet have any evidence that any telomerase activator can make humans live longer, and we won’t have this evidence for a while. All we can say for the moment is that cycloastragenol and some other compounds can elongate telomeres in humans, and that longer telomeres are associated with increased lifespan.

Are There Any Safety Concerns Associated With Taking Telomerase-Activating Drugs?

A telomerase-activating drug has yet to approved for the treatment of any human disease, with many compounds being in the early stages of clinical trials. If the role of telomere shortening in protection against cancer puts you off the idea of taking such a drug, then your concern isn’t unreasonable. Indeed, many researchers are more interested in the idea of deactivating telomerase in order to treat existing cancers, since telomerase is overactive in about 90% of cancer cases. While there’s no evidence that telomerase activators encourage cancer in humans, we’re missing a lot of data. The relative risks and rewards of taking a telomerase-activating drug could depend on many factors such as health status and age.

As for the more short-term side effects of these compounds, those have to be considered on and individual basis. Cycloastragenol doesn’t appear to cause serious side effects and is relatively safe within a certain dose range.

Since many telomerase activators are currently classified as dietary supplements, they aren’t subject to the same safety regulations as conventional drugs. That means it’s ultimately up to the individual to decide if the benefits outweigh the risks. As with any dietary supplement, it’s always a good idea to talk things over with a doctor before you start taking a new compound.


References

Therapeutic Targeting of Telomerase: https://doi.org/10.3390%2Fgenes7070039

Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives: https://doi.org/10.3892/mmr.2019.10614

Telomere shortening rate predicts species life span: https://doi.org/10.1073/pnas.1902452116

Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants: https://doi.org/10.1111/acel.13017

Cycloastragenol extends T cell proliferation by increasing telomerase activity (90.30): https://www.jimmunol.org/content/182/1_Supplement/90.30

Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management: https://doi.org/10.1159/000365290

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence: https://doi.org/10.2174%2F13816128113199990407

Cycloastragenol: An exciting novel candidate for age-associated diseases: https://doi.org/10.3892%2Fetm.2018.6501

A natural product telomerase activator as part of a health maintenance program: metabolic and cardiovascular response: https://doi.org/10.1089/rej.2013.1430

A natural product telomerase activator as part of a health maintenance program: https://doi.org/10.1089/rej.2010.1085

A comprehensive review of cycloastragenol: Biological activity, mechanism of action and structural modifications: https://doi.org/10.1016/j.ejmcr.2022.100060

Cycloastragenol prevents age-related bone loss: Evidence in d-galactose-treated and aged rats: https://doi.org/10.1016/j.biopha.2020.110304

Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis: https://doi.org/10.1002/emmm.201200212

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