Finding the Fountain of Eternal Youth has been a dream of mankind for thousands of years. It’s still science fiction, but anti-aging companies hope to tackle age-related diseases by targeting the underlying biology of aging.
We have been chasing immortality for thousands of years without much success. But a new field of research is fighting aging and helping us and our pets stay healthy as we age.
Age is a major risk factor for common diseases such as dementia, cardiovascular disease, and cancer. Even this year’s coronavirus disease (Covid-19) pandemic proved more dangerous for older people than young people. Anti-aging research is based on the idea that by slowing the aging process, multiple age-related diseases can be prevented at once. The goal is to recreate what happens to supercentenarians, those lucky people. They experience few health problems until they are very old.
The biology of aging is incredibly complex, but researchers have narrowed it down to a list of key factors. Characteristics of agingThis includes destruction of cells, lack of stem cells in tissues, instability of DNA, etc.
Targeting “zombie” cells
Most cells in our bodies are programmed to die after a certain period of time. All the cells that make up our skin are replaced within a month, but the cells in our liver are renewed after a year.
As we age, this regeneration slows down because our cells are no longer able to proliferate. These cells become zombies. The cells are not dead yet, but they are no longer able to perform their functions. This process is known as aging and is thought of as: It underlies the aging process in many of our tissues.
Barcelona-based company Senolytx aims to slow down the aging process by: remove these senescent cells From our organization. “When we are young, we constantly acquire senescent cells.” says Timothy Cash, CSO of Senolytx. “When a wound occurs, senescent cells are formed, but when their role is completed, the cells are removed. When we get older, for some reason senescent cells appear all over the body, but they are not removed.”
The company is developing small molecule drugs called senolytics that remove senescent cells from tissues affected by age-related diseases such as idiopathic pulmonary fibrosis. Currently in the preclinical stage, Senolytx is also developing these drugs for combination therapy in cancer, with the aim of eliminating senescent cells left behind by chemotherapy.
Senolytx is not the only company working on senolytics. In fact, one such drug, developed by the well-known US company Unity Biotechnology, failed to treat osteoarthritis in Phase II this year, a major setback for the field.
Nevertheless, Senolytx also offers other approaches. For example, we are developing drugs such as: Rather than killing senescent cells, they stop them from harming surrounding tissues. Another strategy, licensed to the Swiss company Rejuversen, is to prevent senescent cells from hiding from the immune system. Senescent cells occur more frequently in older people than in young people.
“This can happen because your immune system isn’t good enough to train your immune cells.” Cash told me. “But I think it’s even more likely that the senescent cells have become sneaky and cunning, preventing the immune system from removing them.”
replace old tissue
Aging is thought to occur due to the inability of senescent cells to proliferate. US company AgeX Therapeutics is trying to tackle this problem using pluripotent stem cells. Theoretically, they can split forever.. “We are all descendants of cell lineages that have lasted billions of years.” said Mike West, CEO of US company AgeX Therapeutics.
AgeX develops stem cell therapies for age-related diseases such as cardiovascular disease and type 2 diabetes. According to West, treating these diseases with regenerative cell therapy is similar to treating the aging process itself, like replacing old parts with new ones. “An effective way to keep your car on the road is to replace one of its components.” he told me.
The company converts stem cells into specific types of cells that can replace lost tissue. For example, one of its experimental treatments aims to treat his type 2 diabetes by: Replenish lost brown fat cells.
AgeX is also developing innovative drugs to treat the aging process. These drugs are designed to partially revert adult cells to the stem cell stage, allowing them to proliferate and regenerate damaged tissue. axolotl.
These treatments are also viewed with skepticism by experts in the field. Among the major counterarguments that have been raised is that the aging process is incredibly complex and that aging is an inevitable outcome for all of our cells.
But West is enthusiastic about the possibilities. “Partially returning human cells to regenerative mode has been attempted in several papers.” West told me. “This is certainly a new idea, and skepticism is welcome. It’s fun to do things alone.”
Telomere lengthening
Each time an adult cell divides, the protective ends of chromosomes called telomeres shorten. Once telomeres reach a certain length, cells can no longer replicate and senescence occurs. With the discovery in the 1980s of telomeres and their role in cellular aging, researchers Winner of the Nobel Prize in 2009.
There are now companies developing products that lengthen telomeres to combat aging. Controversial gene therapy It is claimed to have lengthened the telomeres of US CEOs. But Joachim Lingner, a researcher at the Ecole Polytechnique Federal Institute of Technology in Lausanne, says this approach is fraught with risks.
“I think a lot of companies claim that they can manipulate telomere length.” Ringner explained. “However, these drugs have not really been thoroughly tested and it is highly questionable whether they actually have any effect.”
Another big risk of tinkering with telomere length in anti-aging research is that cells can replicate out of control and cause cancer. Paradoxically, this mechanism may keep us alive longer, since telomere shortening limits the number of cells a cell can reproduce.Most cancers Avoid this mechanismThis means this path could be exploited to produce new drugs to treat cancer.
Lingner’s research group compares the telomeres of healthy cells with those of cancer cells and studies the molecular mechanisms behind telomeres. The group had been collaborating with Boehringer Ingelheim to screen potential treatments targeting telomeres, but the big pharmaceutical company ultimately called off the collaboration. “My attempts to get companies interested in this technology were actually quite frustrated – I basically gave up.” said Lingner, who continues his quest to understand the complex biology of telomeres.Despite the limited commercial benefits.
repair mitochondria
Healthy mitochondria are essential for normal cell function. Unlike other structures within cells, mitochondria contain their own DNA, and as we age, mutations can accumulate and become defective.
Daniel Ives, CEO of British company Shift Biosciences, says targeting defective mitochondria may be the most effective way to tackle the aging process.
“imagine that you have a network in which some of the biological hallmarks of aging are better connected than others;” Ives explained. “Mitochondria are a very central feature, the most central of all. If you can influence a central node, you may have undue influence on that network.”
Shift Bioscience is developing small molecule drugs that can repair damage to mitochondrial DNA by utilizing a repair mechanism called the Shift effect.It essentially consists of Force mitochondria to compete They interact with each other for nutrients, ensuring that only healthy mitochondria survive.
“The shift effect evolved to remove mutations in mitochondrial DNA.” Ives explained. Although this phenomenon has been observed for many years, only recently has it been achieved to induce this phenomenon artificially within cells.
The company is targeting MELAS, a rare mitochondrial disease that causes dementia and seizures. This lead drug candidate is currently completing preclinical testing, which, if successful, will lead to Phase I clinical trials in healthy volunteers.
“You probably can’t believe how lucky you were during your first stage exam.” commented Ives. “Not only are you getting paid, you’re also getting paid to take a drug that may have anti-aging effects. This seems like the best deal I’ve ever heard.”
How close are anti-aging treatments?
For anti-aging, recently It began to attract large amounts of investment.For example, google poured money into Amazon’s CEO and Mayo Clinic are backing Unity Biotechnology, while joining US biotech company Calico.
“Investor interest in anti-aging has already peaked.” Cash said. “I don’t see it going any higher. I think it’s at its peak now.”
However, developing anti-aging treatments is currently difficult because aging is not an official disease, according to regulatory authorities such as the EMA and FDA. Therefore, companies need to target specific age-related diseases in each study.The American Federation for Aging Research aims to counter this trend With clinical trial It measures the effects of the approved diabetes drug metformin on not just one but multiple age-related symptoms.
Cash believes the time has come to embrace the aging process as a formal goal of drug development. “Perhaps in the future, if the FDA and EMA motivate us to start considering aging as an indicator, we will be able to use these molecules we discover for age-related diseases for aging in general.,” he added.
Another challenge may be the biotech industry’s approach to finding anti-aging treatments. “Companies are investing in each and every characteristic of aging and saying, “Let’s put a horse in a race that addresses all of these characteristics, and one might do well.” ” Ives said. “This model doesn’t face up to the fact that we don’t know everything there is to know about aging.”
Additionally, there are varying opinions regarding the likelihood of finding anti-aging treatments in the near future. The Phase II failure of Unity Biotechnology’s senolytic drug candidate in osteoarthritis was the latest focus of this discussion. But Cash was enthusiastic about the prospect.
“Some believe that aging is a stochastic process involving so many pathways and processes that we will never find a drug that affects all of them.” He said. “I don’t think the data, the animal genetic data, the pharmacological data, suggests that, doesn’t support that. It actually confirms that we can achieve our individual goals and extend our lives.”
But Ringner wasn’t confident. “I believe that one of the major problems with aging is epigenetic dysregulation, where genetic changes occur and accumulate within cells.” he explained. “This is difficult to undo. I don’t think it’s impossible, but I could be wrong.”
Many of the anti-aging treatments in development have shown promise in animal models such as C. elegans and mice. Although reassuring, these animals age very differently than humans. Organizations and companies developing anti-aging treatments must endure a lengthy clinical trial process to prove that these treatments make a difference in humans.
Until clinical evidence is available, it’s best to keep a critical eye.Scientists seem to agree, at least for now. The best way to stay healthy To last long, you need a healthy diet and regular exercise.
This is an updated version of an article published on April 24, 2019.
Cover illustration by Elena Lesko. Image from Shutterstock.
