Researchers have created a database of all the clinical trials in which researchers have targeted ageing with drugs. A researcher says that there are already indications that the pace of ageing can be slowed.
There was a time when everyone considered ageing to be quite natural and inevitable.
Not so today, when researchers all over the world delve into ageing as a biological process and discover that the process is more susceptible to intervention than previously thought.
In recent decades, many experiments on animals have shown that the ageing processes can progress rapidly but can also be slowed down – with animals living considerably longer.
In the past decade, research breakthroughs have enabled biological ageing to be measured very precisely, and researchers have now embarked on the first experiments with humans.
Some results have been disappointing and others promising, and researchers have therefore established a database of all the completed and ongoing human pharmacological trials aiming to influence the ageing process.
The database provides greater insight into what the research actually shows and what is useful if the goal is to live longer.
“You can search for keywords, drugs or specific clinical trials and thereby find out what the research shows and what the research is trying to determine. Summarising the evidence for interventions targeting ageing enables researchers to access information from one reliable source,” explains the researcher leading the database initiative, Morten Scheibye-Knudsen, Associate Professor, Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
The database, which is available at www.ageingdb.com, has been presented in Ageing Research Reviews.
Biological age can now be measured very precisely
Morten Scheibye-Knudsen says that researchers have identified more than 1,000 small molecules that appear to influence ageing in experimental animals.
The major advances in the field have occurred in recent years because measuring biological age very precisely has become possible by measuring DNA methylation, determining very precisely how old a person’s body really is, even though they may be younger or older chronologically.
“Our research is still at an early stage. Because ageing is not yet an approved indication, drugs cannot be approved yet for targeting ageing. But the more we find out about ageing as a process, the closer we get to ageing not just being an immutable process but one we can influence to live a healthier and longer life,” says Morten Scheibye-Knudsen.
Eliminating old and tired cells
In the database, the researchers have divided the clinical trials aiming to slow the rate of ageing into four groups.
The first group comprises trials with senolytics, a group of drugs that appear to be able to eliminate senescent cells: cells that have lost their original biological function and now just remain as old and tired cells and emit harmful molecules.
The older we get, the more of this type of cell we accumulate, and the number of senescent cells is correlated with how rapidly we age.
“If drugs can eliminate these cells, we suspect that this will positively affect the rate of ageing,” explains Morten Scheibye-Knudsen.
Strengthening metabolism can improve longevity
The second group of clinical trials focuses on substances that affect metabolism – including ones to increase the content of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside, on which Morten Scheibye-Knudsen has carried out clinical trials.
The idea behind increasing the concentration of NAD+ is that it is involved in many enzymatic processes, including repairing cells and the entire cellular energy supply. However, the concentration of NAD+ declines in some tissues with ageing.
“Within this category, some experiments have shown promising results, and it will be interesting to see what the ongoing research will reveal,” says Morten Scheibye-Knudsen.
Antidiabetic drugs may extend life
The third group focuses on drugs normally used to treat people with diabetes, including metformin, GLP-1 receptor agonists and SGLT2 inhibitors.
Data from ageing research have shown that keeping blood sugar low influences some very basic processes that affect the biology of ageing.
These processes change with age but may be able to be kept youthful by treatment with drugs that reduce blood sugar.
“The strongest evidence is within this category because the drugs have been tested on millions of people. Very good evidence indicates that the drugs are not only effective for people with diabetes but also influence many health-related factors and seem to be able to protect against not only high blood sugar but also some typically age-related diseases such as Alzheimer’s and cardiovascular disease,” explains Morten Scheibye-Knudsen.
Morten Scheibye-Knudsen has speculated that GLP-1 receptor agonists may be the first bonafide longevity drugs.
“This is because GLP-1 receptor agonists appear to positively affect some very basic biological processes that weaken as we age,” he says.
Rapalogues extend life for almost all animals
The last category focuses on trials with rapalogues, such as rapamycin, a molecule that is the most effective in improving longevity in nearly all animal experiments.
Rapalogues affect the immune system, and human clinical trials are already underway.
“Rapalogues may be the best drug candidates that can improve longevity, and it will be very interesting if we can find something close to the life-extending effect found in animals,” explains Morten Scheibye-Knudsen.
Summaries of 138 clinical trials
The database includes 138 clinical trials so far, but more will be added.
Most of the trials have not yet been completed, but the few that are completed show that drug treatment prolongs the life of some people with specific diseases.
However, clear evidence is lacking that treating healthy people with drugs or other molecules is reflected in DNA methylation.
“This field is still in its infancy, but knowing so much about experimental animals creates the basis for considerable growth, which we now need to translate to humans. I think that in the coming years we will have the necessary evidence to be able to make clear recommendations on pharmacological interventions in human ageing,” concludes Morten Scheibye-Knudsen.
“Pharmacological interventions in human aging” has been published in Ageing Research Review. The research received support from the Novo Nordisk Foundation, the Nordea Foundation, the Neye Foundation, the Lundbeck Foundation, Denmark’s Ministry of Higher Education and Science, VitaDAO and Insilico Medicine.
