Five technologies in development – including senolytic drugs, rapamycin, stem cell therapy, NAD supplementation and gene therapy – could dramatically slow down aging in the next few years. This report updates the latest developments in these promising and potentially lifespan-extending treatments. [This article first appeared on the website LongevityFacts. Author: Brady Hartman. ]
The longevity science field has made enormous progress in recent years, and human trials of anti-aging compounds have already started, with more to begin soon. The lifespan-extension research field is gaining the attention of mainstream medicine.
The specialists who populate the field, called geroscientists, are developing several technologies that might benefit people who are alive today and aim to bring them to the clinic. These lifespan-extending technologies include stem cell therapy, rapamycin, gene therapy, senolytic drugs, and NAD supplementation.
Focus on Healthspan
While the debate continues on the existence of an upper limit on human lifespan, no one can deny that we are living longer lives than our ancestors. However, we spend a significant portion of our lives suffering from chronic diseases.
That is why geroscientists are shifting their focus from extending lifespan to extending our healthspan instead. Healthspan is a term that describes the portion of our lives in which we live relatively free from chronic disease.
One Disease at a Time Model
In the past, scientists have focused on developing treatments to combat the specific diseases of aging one by one. The good news that medical advances have reduced the impact of many age-related conditions, such as diabetes, stroke and heart disease.
However, some argue that this approach is inefficient. Rather than fighting one disease at a time, some scientists are targeting the underlying processes of aging that drive these conditions.
The last two decades have witnessed a shift in which lifespan-extension scientists are developing treatments that target the fundamental processes of aging that underlie these chronic diseases. These researchers have identified dozens of anti-aging compounds which extend the healthspan and lifespan of laboratory animals, and are now testing them in clinical trials in humans.
One proposed method to extend our healthspan is to kill off senescent cells. These non-functioning cells clog up the tissues of aging bodies and disrupt normal functioning. The numbers of senescent cells in our bodies increases as we grow older, a common hallmark of aging. Senescent cells create chronic inflammation that harms the surrounding tissue. Researchers have implicated senescent cells as a significant cause of age-related diseases such as kidney failure and type 2 diabetes.
Scientists have invented compounds called senolytics that clear senescent cells from the body. Senolytic drugs have reversed aging in mice, and longevity researchers hope they will do the same for humans. Senolytic drugs have shown remarkable benefits in mice, preventing age-related bone loss, improving cardiovascular function and reducing frailty. Moreover, they seem to rejuvenate the appearance and vitality of the rodents.
In a press release, Dr. James Kirkland of the Mayo Clinic advocated for the development of senolytic therapies, saying
“The emerging repertoire of senolytic drugs shows that they are having an impact on a huge range of diseases,” adding “Our goal is to achieve the same success in humans as we have in preclinical animal models in efforts to prevent or delay the conditions associated with aging.”
Senolytic treatments are promising and are prompting human trials. Our friends at the lifespan-extension organization BetterHumans announced they are conducting a human trial of the senolytic combination of dasatinib and quercetin. In fact, the organization is also sponsoring trials of rapamycin and NAD supplementation, numbers 2 and 4 on our list. Moreover, other organizations are further planning to begin human trials of senolytics soon.
Researchers believe that rapamycin therapy can slow down aging in our bodies. Hailing from the exotic shores of Easter Island, the drug rapamycin is a superstar in the anti-aging community. Rapamycin extends lifespans in many ways, one of which is by promoting autophagy in animal studies. Autophagy is a group of cellular processes with many roles, the most important of which is keeping the cell neat and tidy.
Time and again, research studies link efficient autophagy with longer life and superior health. Cellular housekeeping services such as autophagy are essential, and geroscientists have long known that organisms with efficient autophagy have longer lifespans. Rapamycin rejuvenates aging cells, in part, by stimulating autophagy.
The problem with rapamycin is that when taken daily, it causes severe and potentially life-threatening side effects, such as suppressing the immune system and promoting the onset of diabetes. However, researchers have found that intermittent rapamycin therapy seems to avoid suppressing the immune system.
Researchers don’t know yet if intermittent rapamycin therapy will promote diabetes and are conducting a clinical trial of rapamycin in healthy seniors. Moreover, other organizations such as BetterHumans announced they are doing human trials of rapamycin for anti-aging purposes.
3. Stem Cell Therapy
Stem cells are the repairmen of our bodies and divide without limit to produce fresh young cells when needed. Our cells are continually subject to all kinds of damage and eventually die off. In our youth, our bodies use stem cells to replace tissues lost to injury. However, as we age, the number and capabilities of our stem cells decline, and our bodies decay along with them.
For example, researchers have seen that when the stem cells in the brains of mice begin to disappear, they start to develop diseases. To test the rejuvenating power of stem cells, researchers extracted stem cells from the brains of baby mice and injected them into the brains of middle-aged mice.
The researchers who performed this experiment believe that the fresh stem cells reinvigorated the older mice by secreting microRNAs that regulate metabolism. After four months, the experimenters observed that the muscles and brains of the treated rodents performed better than those of untreated ones. As well, the treated mice lived about 10% longer, on average.
Stem cell technology doesn’t just involve transplants. Researchers at the Salk Institute are developing a novel regenerative reprogramming technology that uses Yamanaka factors to rejuvenate tissues while they are still in the body.
Popularized by Harvard professor Dr. David Sinclair, NAD has remarkable rejuvenating effects on mice. Longevity scientists are hoping that NAD will do the same for humans.
Sometimes referred to as ‘the fountain of youth molecule,’ NAD is naturally found in our bodies but decreases significantly as we grow older. Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells and is essential to sustaining life. While plays a role in a myriad of cellular processes, its most notable effects are on energy levels, sirtuins (Dr. David Sinclair’s specialty), DNA repair, and other maintenance and repair processes.
Elysium markets a supplement called Basis that is promoted as maintaining cellular health. Basis is a combination of nicotinamide riboside (NR) and pterostilbene that increases NAD levels in the body. The principal ingredient in this mix appears to be NR.
However, NR isn’t the only way to boost NAD levels. A natural substance called nicotinamide mononucleotide (NMN) does the same thing, and maybe even better. NMN is a NAD precursor, that works like NR to boost NAD levels in the body. Last year, a team of scientists led by Dr. David Sinclair announced that NMN restored the youthfulness and vitality of mice. Moreover, NMN repaired the DNA damage caused by radiation exposure or old age.
While a recent study showed that the Basis supplement increases NAD levels, it was too short in duration to confirm if the supplement rejuvenated the bodies of the study participants. The authors of the study suggest that a double dose of the daily supplement increased mobility among the senior adults who were taking it. However, this result needs to be confirmed in future studies.
5. Gene Therapy
Genetic engineering has held the imagination of scientists and the public alike. Gene therapy is the practice of modifying the human genetic code to treat or prevent a disease. Gene therapy promises to address some of the most devastating illnesses affecting humans.
The advent of CRISPR gave the gene therapy field an enormous push. Techniques to modify the genetic code have existed for several decades, and CRISPR ushered in an era of cheaper, faster and more efficient editing tools. While the original CRISPR is a powerful tool, scientists continue to improve the technology, and a video on CRISPR 2.0 shows us that researchers have improved on the CRISPR gene editing technology. In one example, researchers at MIT performed CRISPR gene editing with nanoparticles.
Unfortunately, recent research suggests that CRISPR may not work for most of us. However, genetic engineers have a tried and true gene editing tool called viral vectors. In fact, most gene therapy clinical trials rely on viral vectors to deliver the desired genetic payload. For example, a recently approved gene therapy for blindness uses a viral vector. In another example, researchers used a viral vector in a gene therapy clinical trial to treat hemophilia A and say they achieved phenomenal results.
Gene therapy also has a darker side. Body hackers are those who refuse to wait for clinical trials to prove that a particular gene therapy is safe and effective. Instead, these folks have resorted to body hacking with gene therapy, a dangerous practice.
Gene therapy cannot only be used to treat a disease; some envision using genetic engineering to tinker with our genetic code to give us longer and healthier lives.
Researchers have identified several hundred genes that can increase the lifespan in animals when modified. In fact, they have linked variations of some of these genes with the exceptional longevity enjoyed by centenarians, the lucky people who live to 100 years or more. In centenarians, these are called longevity assurance genes – variations of specific genes that may allow some people to live longer and healthier lives.
Identification of the genes that delay or prevent the crippling diseases of old age may help researchers develop novel strategies to improve both our lifespans and healthspans. Scientists haven’t identified all of the longevity assurance genes yet, they have identified a few dozen. They have found human gene variants that seem to have a protective effect against certain chronic diseases of aging and are linked to a long life. For example, inheriting a particular version of the gene for the apolipoprotein E (Apo E) may decrease a person’s risk of developing heart disease and Alzheimer’s disease.
Related: Gene editing advances bring us one step closer to making designer babies.
There is no single magic bullet to cure aging. Extending lifespan requires a complex array of different therapies. For example, if scientists kill off enough of our senescent cells, we will need fresh new tissues provided by stem cells to replace the lost ones. In the meantime, supplements such as NAD could help correct our declining metabolism and improve our declining DNA repair processes.
Most of these compounds have been studied using mice for the most part. While they are proof of concepts, there is no guarantee that these lifespan-extension therapies will work the same way on humans. More often than not, promising compounds have shown remarkable results in mice, only to be a flop in human trials, or even worse, harmful.
To bring these compounds from the lab to the clinic, scientists need to perform human trials. The field of lifespan extension needs more funding and attention. If it gets it, we might enjoy growing older without pain.
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Cover photo credit: Getty Images(iStock).
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