Scientific Fact Sheets

Clinical Trials For Healthy Longevity That Are In Progress Or Could Be Started Immediately

One of the main challenges of research for healthy human longevity is to organize reliable studies (double-blind…) and to publish the results (even if they are not positive).

This page gives a list of what the organization Heales considers the most important and promising clinical trials that have already been started or should be started as soon as possible. As the studies are in progress, it is important to keep ourselves updated on the latest news which included criticism from the scientific community.

This list is intended to be a starting point. You are more than welcome to comment or make other suggestions.

An article about trials on animals will be published later.

  1. TRIM study Thymus

The thymus is a primary lymphoid organ essential for the development of T cells. These T cells are majorly responsible for adaptive immunity or the first line of defense against bacteria, viruses, and also tumors in the body. As time passes, the thymus goes under programmed cell atrophy known as involution. All T cells are produced at a young age as the thymus is at its largest size in children. As people grow older, the thymus starts to shrink and involution especially hits the immune system of people between the ages of 65 and 75. Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X) by scientists at Intervene Immune were originally run from 2015 to 2017 on participants from age 50-65 that are healthy men that received a combination of growth hormone DHEA and metformin with an objective of reversing thymic involution. The results were promising they show that the participants showed an increase of more than two years in the predicted human lifespan. This was seen throughout the various epigenetic clocks including the GrimAge clock that analyzes DNA methylation. As of today, they have started another trial with similar objectives and are currently looking for volunteers. FDA has not approved this therapy yet but TRIIM-X Trial was the first of its kind to show regression in multiple age-related biomarkers possible in humans.

2.  Metformin TAME Study 

First introduced in 1922, Metformin is a well-known drug given to patients with type 2 diabetes and is known to act by helping the body to reabsorb less sugar and hence balance the blood sugar levels. It both lowers glucose absorption after a meal, as well as increases the body’s sensitivity to insulin. It is a popular medicine as it is cheap in cost and has minimal side effects. Metformin has already shown signs of delaying aging The main aim of the TAME (Targeting age with Metformin) Trial is to study how metformin delays age-related diseases like CVD, neurological conditions, cancer, etc. Led by Dr. Nir Barzilai, the trial is set to be six years long with more than 3000 participants from the age 65 to 79. Their goal is that if the FDA declares ‘aging’ itself as a disease, then instead of targeting the different age-related conditions, they will target aging itself which will include all the conditions together.Along with the TAME trial, they also want to look for biomarkers of aging in TAME BIO by:

  • Store samples of the blood, urine, DNA, etc from all the participants to study further.
  • Use different approaches to study biomarkers that predict changes in function, multi-morbidity, and subsequent death.
  • Study the influence of Metformin on multiple age-related biomarkers on all participants using and create a report with the core data collected.

They are currently collecting funds to proceed with the trial as the TAME Trail team deeply believes that drug intervention for aging and related diseases will not only extend years of health but will also save trillions of dollars. 

3. Rapamycin

Also known as Sirolimus, Rapamycin is a macrolide compound used for preventing rejection after organ transplant, coating stents, and even as a treatment for lung and other types of cancer. It functions by targeting the mTOR which regulates the growth of our cells by binding to a subset in the catalytic cycle, blocking the function of the mTOR.

Rapamycin is currently the wonder drug with the most promising anti-aging effects.  The latest studies at the Max Planck Institute for Biology of Aging show that in young adult fruit flies, a 2-week administration of rapamycin can protect them against age-related conditions in the intestine and extend life. Then they administered rapamycin for 3 months in mice and saw similar results with beneficial intestine-related results by the time the mice were middle-aged. This short exposure to the drug is seen to be equally beneficial as lifelong administration with lesser to no side effects. Further studies will now try to answer if the geroprotective effect of rapamycin continues in humans if they start taking it later in life and what kind of dosing will be ideal.

4. Senolytics

Senolytics come under a class of drugs that clears out senescence cells (SC). Senescence is a phenomenon where the cells get arrested in the cell cycle if they sense danger stimuli. Accumulation of the SC increases with aging and can cause damage to the tissue and can be a cause of multiple diseases including various neurodegenerative diseases. 

Dasatinib (a tyrosine kinase inhibitor), Quercetin (a naturally occurring flavonoid), Fisetin, and Navitoclax were the first senolytic-drugs introduced in the market following a hypothesis-driven approach. A combination of Dasatinib and Quercetin was given to mice for over two years and the results showed fewer senescence-related biomarkers as well as a lower occurrence of disc degeneration. However, this result was seen in young and middle-aged mice, not the older ones. The challenge currently lies in the lack of biomarkers specific to senescent cells. Currently, SA-β-Gal is the only available biomarker. Poor drug specificity delivery system is another challenge that the researcher needs to work out. More than 20 different clinical trials are being held to improve the efficiency of senolytics and the results from these will form a promising future.

5. NAD+ Charles Brenner

Nicotinamide adenine dinucleotide (NAD) is a coenzyme for redox reactions and is responsible for transferring electrons during metabolic processes. According to the study of Dr. Chareles Brenner, Nicotinamide riboside (NR) goes into the cells and nucleoside kinase puts a phosphate on by which NR is turned into NMN (Nicotinamide mononucleotide). NMN then converts to NAD and finally to NADP

6. Plasma dilution 

It is a method where the blood from an individual is extracted and then a plasma fraction of that blood is replaced by saline and albumin and this new mix is reintroduced in the body. Plasma dilution, also known as neutral blood exchange, is said to have properties that can restart the body’s regenerative capacities. 

The latest clinical trial from the University of California shows that Therapeutic plasma exchange (TPE) has the potential to restore the younger system and reduce biological aging. This study had a very small group of participants (Only 8) but has promising results with the de-regulation of 10 novel biomarkers, a youthful shift to various age-related conditions showing apoptotic regulators, and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Further studies with the biggest participant group will confirm these results to be favorable in reducing aging.

7. Telomere

According to the Hayflick limit, we know that human cells will replicate for only a limited time and this was confirmed when scientists discovered that telomers shortens after each replication. Telomere has the function of protecting the ends of the genome from degradation and maintaining its integrity of it. Telomerase is the enzyme that catalyzes the extension of the telomeric region and the shortening of this telomeric region is associated with signaling between somatic cells for senescence. 

Shortening of telomere with age is related to factors like apoptosis, and oncogenic transformation and even affects the life and health span. The TACTIC (Telomerase ACTivator to reverse Immunosenescence in Acute Coronary Syndrome) trial from the UK had the objective to check if TA-65MD, a telomerase activator can decrease reduce the shortening of telomerase and oxidative stress.90 Patients took 1 x capsule twice daily for 1 year which may be either the test drug TA65MD (8mg) or the place. Another Clinical Trial from France Telomeres and Arterial Aging (TELARTA). Their objective is to create a model that makes it possible to examine different elements of telomere length dynamics in different tissues: leukocytes, skeletal muscle, endothelial progenitor cells (EPCs), and skin or subcutaneous fat in patients with or without atherosclerosis. The results from these and many such trials will give us a better view of future treatments. 

8. Follistatin 

Activin binding protein, follistatin, is encoded by the FST gene in humans and it is an autocrine glycoprotein, seen in most tissues. It is an antagonist of myostatin involved in increasing strength and muscle mass. This is one of the reasons why follistatin supplements are popular amongst bodybuilders.  

Follistatin gene therapy is emerging and Bioviva CEO (in 2015) became the patient zero for the therapy of both telomerase (hTERT) and follistatin (FST). A study using Mouse mouse cytomegalovirus (MCMV) carrying exogenous FST has shown an increase of 32.5% in median lifespan. Another study targeting Sarcopenia (loss of muscle mass and strength over age) showed overexpression of follistatin delivered by Adeno-associated virus (AAV) in mice aged 24-27 months caused an increase in muscle weight as well as improvement in age-related degeneration at the neuromuscular junction in mice.

9. Alpha-Ketoglutarate (AKG)

AKG is a ketone derivative of glutaric acid which is known to be used by the growing cells and is involved in the healing of wounds and injury (especially muscle tissues). As AKG is an endogenous intermediary metabolite in the Krebs cycle whose levels naturally decline during aging, many supplements are currently available for the public. Rejuvant, is a  potential life-extending compound formulation with alpha-ketoglutarate and vitamins, which has been shown to have an average of 8-year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. 

10. Khloto

Klotho is a transmembrane protein that is involved in the regulation of oxidative stress, signaling growth factors, organ protection, and control over the sensitivity of organisms to insulin and shows involvement in the aging process. 

Current studies show that higher Klotho levels in an 85-year-old will have the same size of brain and the thinking ability to that as someone who is 10 years younger. Another study shows that a 20%-30% increase in the lifespan of animals was observed after the overexpression of Klotho. With a single injection, Klotho showed improved cognition by 2 years in terms of spatial and working memory. Klotho Therapeutics is one of the leading biotech firms which strongly believes in Klotho having anti-aging properties and developing a patent-pending Klotho protein that has great potential to redefine society’s experience with aging.