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Summary: Aubrey de Grey’s SENS foundation is both controversial and inspirational. Watch a 3-minute video of Aubrey, followed by a discussion of Dr. Aubrey de Grey’s revolutionary plans to reverse aging. [This article first appeared on LongevityFacts.com. Author: Brady Hartman. Follow us on Reddit | Google+ | Facebook. ]

Aubrey de Grey is on a mission to reverse aging and has a large group of followers who think he might do it.

In a video interview with the Swiss Innovation Forum a few days ago, Aubrey explains the mission of his SENS Research Foundation in simple language. Later on, you’ll read about the details of his revolutionary plans for rejuvenation science.

With his long beard and eccentric appearance, Aubrey de Grey, Ph.D., is one of the most recognizable people in the geroscience movement. Dr. de Grey is a favorite of transhumanists and has become famous for making statements such as

“the first person to live to 1,000 years old is alive today.”

There’s something of the Old Testament prophet about Aubrey de Grey, who cultivates an eccentric look that is calculated to reassure people that he’s not in the longevity field to get rich. To the contrary, Dr. de Grey has handed most of his wealth over to his charitable organization, the SENS Research Foundation, based in Mountain View, California. SENS stands for ‘Strategies For Engineered Negligible Senescence.’

How to Slow Down Aging

In a video interview with Swiss Innovation Forum (SIF), Aubrey gives us a bird’s eye view of the goal of SENS. When asked about what people can do to prevent aging and keep from getting sick as they get older, Aubrey de Grey explains the SENS strategy in simple terms, saying

“What we can do is just the same as we already do successfully with cars or airplanes. We can periodically eliminate damage from the body every so often so that the overall amount of damage that the body contains is within the manageable quantity – the amount that the body is set up to tolerate without being sick.”

Here is the 3-minute video with Aubrey de Grey. While the video gives a brief introduction to SENS and does not detail all of the revolutionary lifespan extension suggestions espoused by Aubrey de Grey and SENS. A more in-depth explanation of the SENS strategies follows the video. If you have problems viewing, here is the direct link.

Aubrey de Grey’s Revolutionary Plans

Aubrey riles against the widely held view that aging is miserable and unavoidable, and our bodies are merely disposable vessels designed to carry our genes into the next generation.

Dr. de Grey thinks people deliberately block out any serious discussion on aging, putting its horrors out of their minds. He thinks this is because most of us associate aging with ill health. We have a vision of rotting away with Alzheimer’s disease in a vile smelling nursing home. In Aubrey de Grey’s view, suffering in poor health in old age is not necessary and instead, growing to an extreme old age in good health is close to being achieved. As Aubrey de Grey says in the recent SIF interview,

“Aging is certainly something bad because if it’s the reason why we get sick when we get old without aging we wouldn’t get Alzheimer’s disease and I’m fairly sure that you won’t want to get Alzheimer’s disease.”

Aubrey de Grey’s SENS Research Foundation

To put his ideas into practice, Aubrey de Grey started the SENS Research Foundation as a public charity to transform the way the world views and treats age-related diseases. The concept of negligible senescence comes from the book “Longevity, Senescence, and the Genome” written by Caleb Finch. In his manuscript, Finch pointed out that some animals – most notably jellyfish and lobsters – don’t seem to visibly age at all.

SENS is both an outreach and research organization that believes in the promise of the damage-repair approach to treating age-related disease. SENS funds research at university labs around the world and its research center near its headquarters. Both Aubrey de Grey and SENS believe that a world free of age-related disease is possible.

Aubrey de Grey and SENS both believe that the focus of longevity research and practice should be a strategy of whole-body tissue rejuvenation and repair. SENS is a strategy of repairing damage and degradation and thereby pre-empting the diseases that accompany aging.

Dr. de Grey has written multiple papers and books, which have influenced many. Partly as a result of his efforts, geroscience is ‘going mainstream, ’ and researchers in the field, called geroscientists are gaining respect and fame, including such notables as David Sinclair and Nir Barzilai (famous for the TAME trial).

Moreover, if his life extension plans don’t work out, Aubrey de Grey has a backup plan. Along with such notables as Ray Kurzweil, Dr. de Grey and has signed up for cryonics with the industry-leading firm Alcor. Aubrey has arranged for the cryopreservation of his body shortly after death, with the hopes of being revived when medical science has found a cure for whatever felled him. While the transhumanist practice of cryonics is a decidedly unproven technology, Dr. Grey proposes other technologies to keep us alive so we won’t need to be cryopreserved.

Technologies that Reverse Aging in Some Tissues

Aubrey de Grey and SENS has attracted a massive following of lifespan extension enthusiasts who believe that technologies such as tissue rejuvenation, organ replacement, molecular repair, stem cell therapy, and geroprotective pharmaceuticals, such as rapamycin therapy and metformin can alter our fundamental biology in a way that reverses aging in many tissues and significantly increases our healthy lifespan.

In the recent SIF interview, Aubrey de Grey gives us an update on the progress made thus far in bringing the SENS rejuvenation strategies to the clinic, saying,

“Pretty much all of the therapies that we need – the damage repair therapies – don’t yet exist. Some of them do exist in a preliminary form, anyway. So, for example, stem cell therapies are around and being trialed in the clinic to actually repair some of the damage of aging like in Parkinson’s disease for example. But the reason why the organization – SENS Research Foundation (that I’m the chief science officer of) the reason we exist is because plenty more basic research is still needed to do the early stage parts of developing the other damage repair medicines that we need.”

The SENS foundation believes that regenerative medicine will repair the damage that underlies the diseases of aging, and focuses its research energies on developing these technologies. The goal of SENS is to stimulate the growth of a biotech industry that will cure these conditions. The SENS research approach emphasizes the application of regenerative medicine to age-related disease, with the intent of repairing the underlying damage to the body’s cells and tissues.

Many things go wrong with aging bodies and at the root of all these problems is the decades of unrepaired damage to the cellular and molecular structures that make up our tissues called macromolecular damage. As these structures degrade, our tissue function becomes progressively compromised, leading to the diseases and disabilities of old age.

The SENS strategy proposes the use of regenerative medicine to prevent and reverse aging and the ill health that accompanies it. In the SENS way of thinking, the best course of action is to repair aging damage at the level where it occurs. Both Aubrey de Grey and SENS advocate the development of regenerative therapies that remove, repair, replace, or render harmless the molecular and cellular damage that has accumulates with aging. By restoring order to the living machinery of our tissues, these rejuvenation biotechnologies will restore the normal functioning of the body’s cells and essential biomolecules, reverse aging in some tissues, bringing the body back to a state of youthful vigor.

Seven Undeadly SENS

As part of his SENS strategy, Aubrey de Grey has identified seven forms of cellular and molecular damage that accumulates over time, causing decay and eventual death. Dr. de Grey has an unshakeable vision of how to repair this damage and reverse aging. Aubrey firmly states there are only seven types of molecular and cellular damage, and proposes specific ways to tackle them as follows:

SENS #1. Stem Cell Therapy to Replace Lost Tissue

As we age, we lose cells due to programmed cell death, leading to tissue atrophy. Stem cells are the repairmen of our bodies and replace the lost ones. Unfortunately, our repairmen also go into decline as we age, and stem cell decline leads to a shortage of replacement cells. Researchers have blamed a shortage of cells in neurodegenerative disorders such as Alzheimer’s Disease and Parkinson’s and the degradation of our immune systems.

Aubrey recommends replacing these cells using stem cell therapy which can grow brand new cells. New cells will reverse aging in specific tissues. Dr. de Grey advocates stem cell therapy, saying it will play a significant role in rejuvenating our bodies.

SENS #2. Depriving Cancerous Cells of Telomerase

Aubrey de Grey acknowledges that changes to nuclear DNA are a big problem as they lead to cancers which are responsible for about a quarter of all human deaths.

Residing in the nucleus of our cells, nuclear DNA holds the blueprints for building our bodies and regulates the production of proteins and processes that make us who we are. Mutations in nuclear DNA build up as we age, the result of continuous DNA damage paired with declining DNA repair mechanisms.

Other than causing cancer, Aubrey does not believe that nuclear DNA mutations cause aging, a view that is in stark contrast to that of most scientists.

Aubrey’s strategy to protect us against tumors is based on a chink in their armor. Because tumors reproduce at a furious pace, they quickly reach the ends of their telomeres. Cancer cells need to renew their telomeres to keep up the bad work.

Looking very much like the plastic tips on the ends of shoelaces, telomeres are caps that protect the ends of our chromosomes that keep them from unraveling. The telomeres of normal cells wear down with each cellular division, and when a cell runs out of telomeres, it quickly self-destructs. After 50 to 70 divisions, the telomeres of a healthy cell reach their limit, and the cell stops dividing, causing it to commit a form of programmed cell death.

Unlike healthy cells which play by the rules, cancerous cells have found ingenious ways to lengthen their telomeres to keep going. Cancer cells have evolved mutations that exploit one of the cell’s two systems for renewing telomeres: they do this primarily by using telomerase to lengthen their telomeres, and infrequently by using a process called Alternative Lengthening of Telomeres (ALT).

Aubrey de Grey’s SENS strategy targets the need for cancer cells to renew their telomeres. He calls this strategy WILT, which stands for “Whole-body Interdiction of Lengthening of Telomeres”. The idea behind WILT is bold and controversial. Genetic engineers prevent cancer by pre-emptively removing our genes for the telomere-lengthening machinery altogether. The result is that tumors can’t exploit telomerase and ALT to keep themselves alive.

This strategy could run into trouble because our body’s stem cells also use telomerase to stay immortal.

SENS #3. ‘Backing Up’ Mitochondrial DNA

Aubrey believes that mutations in mitochondrial DNA (mtDNA) are a significant cause of aging. Mitochondria do not possess highly tuned repair mechanisms and as a result, are prone to more rapid damage accumulation. Accepting the fact that mitochondrial mutations will occasionally happen, Aubrey de Grey suggests engineering a system that prevents the harm they cause to the cell.

Aubrey de Grey’s strategy is to accomplish this by putting backup copies of the mitochondrial genes into the nucleus – an area that is much better protected – where they cannot be damaged by free radicals generated in the mitochondria. This way, even if the original genes in the mitochondria are deleted, backup copies are available. The genes supply the proteins that keep energy production going, allowing the power plants of our cells to continue business as usual and preventing them from entering into a mutant, toxic state. This approach is called “allotopic expression of proteins.”

The SENS foundation reports some success using this strategy and has shown that two genes essential in mitochondrial functioning – named ATP6 and ATP8 – can be successfully expressed directly in the nucleus. Furthermore, the biotech company Gensight Biologics is currently working on a clinical program to express the essential mitochondrial gene called ND4 in the nucleus of the cell to prevent retinal disease.

SENS #4. Clearing Out Senescent Cells

There is no doubt that senescent cells make us old. These are the walking dead of our tissues – damaged cells that refuse to commit suicide through programmed cell death. Even though there are few senescent cells relative to healthy cells, their effect is devastating. Senescent cells cause all kinds of trouble throughout the body and generate chronic inflammation called inflammaging. Senescent cells have also been implicated in cancers and type 2 diabetes.

Getting rid of senescent cells reverses aging or least some aspects of it. Scientists have found a way to free our bodies of these troubling cells using small-molecule drugs called senolytics. An amalgam of the words senescence (growing old) and lytic (to destroy), senolytics selectively destroy these zombie cells. Reducing the number of senescent cells produces a corresponding reduction in the symptoms of inflammatory diseases. Senescent cells generate inflammation-stimulating messengers via a mechanism known as the senescent-associated secretory phenotype (SASP).

SENS #5. Unlinking Crosslinked Proteins

As we age, our proteins become jumbled up and tangled due to a phenomenon known as crosslinks. This occurs outside the cells when too many connections are formed between the proteins.The primary culprit is due to increasing levels of advanced glycation end-products (AGEs), produced when sugar forms an unhealthy attachment to the proteins that make up the structures in our bodies.This causes tissues to lose elasticity, and has been linked to hardening of the arteries, also called arteriosclerosis and wrinkling of the skin.

Getting rid of these crosslinked proteins reverses aging aspects, and that’s why Dr. Aubrey de Grey’s SENS foundation is developing drugs to break these crosslinks.

SENS #6. Throwing Out Extracellular Junk

Extracellular junk is another form of garbage which resides outside of cells. An example of extracellular junk are the amyloid plaques in Alzheimer’s disease.

Aubrey de Grey and SENS both advocate using antibodies to remove this rubbish.

SENS #7. Put Cellular Junk into the Garbage Disposal

Dr. de Grey calls this garbage ‘intracellular aggregates’ because it is the junk that cells generate but lack the housekeeping mechanisms. Mainstream researchers have documented the problem of cellular junk and its role in aging, calling the phenomenon ‘cellular garb-aging.’ These aggregates not only accelerate aging, but they are also implicated in cardiovascular disease, Alzheimer’s and macular degeneration.

Aubrey de Grey and SENS propose bolstering a tiny organelle called the lysosome, the cell’s garbage disposal unit, by adding new enzymes to better dispose of this cellular debris.

Sailing the Seven SENS

The above list is a small sampling of the research projects that Aubrey de Grey’s SENS Research Foundation is involved in. The foundation is involved in a myriad of other research projects. For example, to restore thymus function in the middle-aged, the SENS foundation funds research that uses stem cells to reseed tissue scaffolds to grow a new thymus.

Aubrey de Grey’s SENS foundation defends the preceding list of seven sources of aging damage, saying,

“Decades of research in aging people and experimental animals has established that there are no more than seven major classes of such cellular and molecular damage,” adding “We can be confident that this list is complete, first and foremost because of the fact that scientists have not discovered any new kinds of aging damage in nearly a generation of research, despite the increasing number of centers and scientists dedicated to studying the matter, and the use of increasingly powerful tools to examine the aging body. In its own way, each of these kinds of damage make our bodies frail, and contribute to the rising frailty and ill-health that appears in our sixth decade of life and accelerates thereafter.”

Critics of Aubrey De Grey and SENS

Aubrey and his foundation have no shortage of critics, most of who refuse to believe that some of the strategies he proposes are remotely possible in the near future, such backing up mitochondrial DNA and Whole-body Interdiction of Lengthening of Telomeres.In fact, a decade ago, a group of prominent scientists penned an open letter describing the SENS strategy as pseudoscience.

Even these critics must admit that some of Aubrey de Grey’s prophecies are slowly making their way to the clinic. One shining example is that of senolytic drugs. The compounds have already cleared out senescent cells in middle-aged mice, keeping them looking like far younger ones. Some of the more promising senolytic compounds are currently in clinical trials.

Say what you will about Aubrey de Grey, but one of his greatest strengths is to challenge conventional thinking. All innovative ideas appear to be lunacy at some point.

While Aubrey’s seven strategies of SENS may not all bear fruit, Dr. de Grey is overcoming the inertia that has long kept longevity science subdued.

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References

“A Reimagined Research Strategy For Aging | Sens Research …” SENS Research Foundation. Web. 19 Nov. 2017. Link.

Swiss Innovation Forum. “SIF 2017: Aubrey De Grey.” Youtube. Nov 16, 2017. Link.

Cover photo and all images are screenshots from “SIF 2017: Aubrey De Grey.”

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