Ageing has long been considered an inevitable process; however, scientists may soon have drugs available that may slow or even reverse it.
A team led by Nobel laureate Shinya Yamanaka has discovered that certain factors can help reverse epigenetic markers associated with aging, but some experts warn against premature claims of age reversal.
What Is It?
Researchers are constantly searching for ways to extend and improve human lives, and they’re getting ever closer to discovering a Fountain of Youth than ever. According to a new study published in Aging, scientists are one step closer to reversing effects of aging through chemical approaches used to reprogram cells back to younger states – an incredible milestone in longevity research!
Scientists used temporary “cuts” in mice DNA that simulate damage caused by lifestyle and environmental factors that shorten lifespan, thus reversing genetic activity in these organisms and stopping cellular aging while changing certain biomarkers associated with ageing.
Even with such an exciting discovery, researchers caution that their study is far from being applicable to human patients. For example, it remains unknown if any of the six chemicals studied could actually work without leading to cancerous mutations in human cells.
Unknown is whether or not a cocktail of six chemicals could actually restore youthfulness by undoing damage caused by time to an individual’s epigenetic record, though testing will likely be needed if this treatment proves successful in humans to ensure there are no side effects like cancer or other health complications.
Studies conducted in the past by researchers have demonstrated that caloric restriction, plant-based diets, exercise, high quality sleep and specific molecules can all play a part in slowing or even reversing an individual’s biological age. Thus the six chemicals could potentially have similar results while perhaps being more potent; however many experts remain skeptic of such reverse aging process human trials and whether “rewinding” someone’s clock with pills.
Why Is It Important?
No matter if you follow Bryan Johnson and his $2-million-per-year longevity clinics or simply hope to live longer, recent developments in medicine give hope that we may all age more gracefully – such as research that might reverse rather than simply slow the aging process itself.
This research is founded on the notion that aging results from gradual erosion of epigenetic marks – chemical tags attached to DNA that regulate gene activity and cell type – over time. Damage and mutation can reduce these tags’ effectiveness; some scientists who were not part of this research claim reversing aging is premature since their presence cannot be restored without leading to cancerous cells forming again.
Researchers have developed ways to combat aging in rodents. One such experiment at Cold Spring Harbor Laboratory discovered that metformin can extend mouse lives by decreasing accumulations of damaged/mutated senescent cells which release proinflammatory signals leading to diseases.
Genetic or pharmaceutical interventions known as senolytics (removal of senescent cells) may help protect against diseases associated with aging such as diabetes and cardiovascular disease by eliminating them. Many drugs and natural compounds that reduce accumulations of senescent cells in humans already undergo clinical trials; such as metformin, NAD+ precursors, glucagon-like peptide 1 receptor agonists, TORC1 inhibitors, Spermidine and Rapamycin to name just some examples.
At the core of all these therapies is a drug capable of targeting and inhibiting the mTOR pathway – an essential molecular signaling cascade in cells which regulates protein synthesis as well as many other fundamental functions. Rapamycin was first isolated from an Easter Island bacteria; today it serves antifungal, immunosuppressant, anticancer properties as well as decreasing glucose in blood, thus decreasing insulin and triglyceride levels.
Sinclair and her team analyzed existing medicines to discover compounds that interact with mTOR to rejuvenate fully matured cells, and they discovered six cocktail formulations which could de-age mouse and human cells within four days – as well as lower or reverse transcriptional and genomic markers of cell ageing – suggesting they may have similar effects in humans. Furthermore, these drugs are already widely prescribed to patients so their safety should allow for rapid implementation into larger scale human trials more rapidly.
How Will It Work?
At present, numerous drugs and natural compounds exist that can slow or even reverse some aspects of aging, while also having broad disease-preventing or attenuating properties. Therefore, it’s likely that some will eventually be approved as anti-ageing medicines.
Metformin, commonly prescribed to treat diabetes, has been found to extend life span and decrease cancer risks in mice. It works by blocking accumulations of damaged and non-dividing senescent cells which contribute to chronic diseases like cancer or Alzheimer’s.
Researchers have also recently created a class of drugs known as “senolytics”, designed to eliminate senescent cells. Human trials for this new class of meds are underway and it could potentially become available within 10 years.
Researchers continue their efforts to slow aging and improve health through other avenues, like reprogramming mature T cells to act like stem cells; a team at Cold Spring Harbor Laboratory discovered this approach could help slow aging while also protecting against disease such as diabetes and neurodegenerative disorders.
Other methods to reverse aging are also being explored, including gene therapy, telomere repair, mitochondrial rejuvenation and cellular senescence reduction. These approaches involve manipulating gene expression levels or clearing damaged DNA fragments from cells; as well as decreasing inflammation levels and improving energy metabolism.
However, not all longevity experts are enthusiastic about the recent studies. A few caution that their claims are premature and exaggerated.
Biogerontologist at University of California Berkeley pointed out that these studies only comprised tests of six cocktails of chemical compounds and that authors should have validated them by showing improvements in health metrics or lifespan in animals prior to making such bold claims.
Matt Kaeberlein, professor and director of the Healthy Longevity Institute at the University of Sydney, concurred. He mentioned how taking one pill might not extend lifespan significantly but that targeting issues like inflammation and mitochondrial dysfunction could make an important impactful difference in people’s lifespans.
What Are the Side Effects?
There has been great interest in lengthening life, yet science to reverse the aging process isn’t ready for humans yet. Instead, researchers are working towards treating diseases and injuries which become more prevalent with age in order to stave off death for longer lives.
Some scientists, such as Harvard geneticist David Sinclair, believe that reverse aging might eventually result in pills to keep people healthy for much longer. To do so, one must erase the damage time has done to our epigenetic records, so our genes act younger again.
Reprogramming cells to become stem cells and then into whatever type of cell they need to become is the key to reversed aging in mice, according to scientists in Sinclair’s lab. They genetically engineered a virus with rejuvenating Yamanaka factors and used this strategy on retinal ganglion cells at the back of mouse eyes – successfully rejuvenating damaged cells while growing new axons! Since then, their team has also addressed epigenetic changes related to aging muscle and kidney tissues of other mice while working on reversed aging completely within their whole mouse bodies!
Sinclair notes that human gene therapy won’t become practical any time soon; however, companies such as Tally Health and Rejuvenate Bio are already offering epigenetic approaches to anti-ageing directly to consumers. They provide cheek-swab tests to estimate an individual’s biological age (which relates to how their genes make them look aged), then use those results to recommend lifestyle interventions and medications that could slow or reverse predicted biological aging.
Other biologists have met these claims with caution. Matt Kaeberlein, a gerontologist from University of California Berkeley, advises that any claims of biological aging reversal be validated first in human trials with improvements seen in age-related health metrics or lifespan measures before making grandiose statements of its reversement.
On a related note, he emphasizes the need for rigorous safety tests on drug and supplement combinations used in these studies, particularly regarding potential side effects such as CHIR99021’s ability to inhibit glycogen formation during sleep in order to store energy, tranylcypromine’s potential liver-damaging properties, and valproic acid’s capacity to cause seizures in some individuals as compounds with potential side effects that should be carefully tested for side effects.
