Strategies for Engineered Negligible Senescence

The Strategies for Engineered Negligible Senescence, or SENS, is the name given to a research and advocacy program that aims to develop a cure for aging. This will take the form of a package of therapies and biotechnologies capable of repairing the known forms of cellular and molecular damage that accumulate in our bodies with age, and are thus most likely the root causes of aging. This may sound ambitious indeed, but read on: you'll find that the research community is closer to being able to realize this goal than you might imagine.

An Introduction to SENS

At present the Strategies for Engineered Negligible Senescence (SENS) are a synthesis of the following items: a scientific research program carried out under the auspices of the SENS Research Foundation and involving a number of laboratories and researchers around the world; a wide range of existing life science knowledge produced over the past decades; a call to action for the public and the scientific community; and the SENS proposals first put forward by biomedical gerontologist Aubrey de Grey.

SENS is of great importance for those of us who are interested in living much longer, healthier lives. The crucial, central point of the SENS vision is that scientists already know more than enough to be working on the development of therapies that can reverse the root causes of age-related degeneration. There is no reason or need to delay this work. SENS provides a roadmap for the near future of rejuvenation research, as well as ethical and utilitarian arguments for moving to defeat age-related degeneration as rapidly as possible. The SENS initiative has been growing over the past decade and now has the support of prominent philanthropists and life scientists.

If you'd like a complete description of SENS from top to bottom, Aubrey de Grey and Michael Rae have written Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. In that book they explain, as best we know based on the biotechnology and scientific knowledge of today, how we can band together, build a mighty research infrastructure, and greatly extend our healthy life spans soon enough to matter. Ending Aging is perhaps the best introduction to the science and rationale of SENS, and is highly recommended.

The Science of SENS

It is proposed that there are most likely only seven categories of biological process that lead to degenerative aging and age-related disease, all of which have been known for at least twenty years. That no new categories have been discovered since the late 1980s - over a time of great progress in all fields of biology and medicine - strongly suggests that there are no other significant causes of age-related degeneration and disease. Scientists can already describe potential therapies that could address each of these processes. The basic tools required for these therapies have in many cases already been demonstrated in the laboratory or in trials for more limited uses. A list follows:

1) Some tissues lose cells with advancing age, like the heart and areas of the brain. Stem cell research and regenerative medicine are already providing very promising answers to degeneration through cell loss.

2) We must eliminate the telomere-related mechanisms that lead to cancer. One possibility is to selectively modifying our telomere elongation genes by using targeted gene therapies.

3) Mitochondrial DNA is outside the cellular nucleus and accumulates damage with age that impairs its critical functions. The SENS approach is to use gene therapy to copy mitochondrial DNA into the cellular nucleus. There are other strategies for manipulating and repairing damaged mitochondrial DNA in situ some first demonstrated as early as 2005.

4) Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions that degrade their effectiveness. Scientists can search for suitable enzymes or compounds to break down problem proteins that the body cannot handle.

5) Certain classes of senescent cell accumulate where they are not wanted, such as in the joints. We could in principle use immune therapies to tailor our immune systems to destroy cells as they become senescent and thus prevent any related problems.

6) As we age, junk material known as amyloid accumulates outside cells. Immune therapies (vaccines) are currently under development for Alzheimer's, a condition featuring prominent amyloid plaques, and similar efforts could be applied to other classes of extracellular junk material.

7) Junk material builds up within non-dividing, long-life span cells, impairing functions and causing damage. The biochemistry of this junk is fairly well understood; the problem lies in developing a therapy to break down the unwanted material. The SENS approach here is to search for suitable non-toxic microbial enzymes in soil bacteria that could be safely introduced into human cells.

If you have an interest in the science of SENS, you will find explanations and references at the SENS Research Foundation website and a detailed guide to SENS in the book Ending Aging.

The State of Progress in SENS

Modest philanthropic funding for SENS research commenced in 2005 under the administration of the Methuselah Foundation, and the total funds raised grew to more than $7 million by 2009 - and kept going. By 2010, the SENS Research Foundation's yearly expenditures topped $1 million, in 2012 more than $3 million, and as of 2015 the annual budget of the SENS Research Foundation is about $5 million, a tenth of that of comparable research institutions in the mainstream of aging science such as the Buck Institute. The pace of progress on work that is funded only within the SENS research community is consequently slow in comparison, and one of the principle aims of the SENS Research Foundation staff is to ensure that they are not the only group coordinating and funding this research. There is far too much to accomplish for any one organization.

The SENS research portfolio incorporates some lines of work that are well funded and widely supported, however. In the stem cell research community many groups are making progress on understanding why stem cell activity declines with age and how to safely intervene in this process. Additionally, similarly broadly supported work on the replacement of stem cells and enhancement of regeneration in aged and damaged tissue is taking place. Since the majority of potential regenerative treatments emerging from stem cell research target age-related disease, scientists must solve the problems of stem cell aging in order for therapies to work effectively. The cancer research community is as well funded and energetic as the stem cell field, and here too there are lines of work that will lead to robust treatments for many different types of cancer in time. The Alzheimer's research community is also heavily funded, and in this case the most interesting work from a SENS perspective is the development of immunotherapies to clear amyloid from the brain. This has proven to be a challenging goal, with only failures so far at the clinical trial stage despite the time and money invested, but at the end of the day the outcome will be a general technology platform that can be turned to address other forms of amyloid in the body, and thus remove their contributions to degenerative aging.

Concrete progress is also occurring in some of the poorly funded areas of SENS rejuvenation biotechnologies, albeit at a far slower pace. In 2014 and 2015 researchers produced technology demonstrations for senescent cell clearance treatments, showing benefits to health in normal aged laboratory mice, and received considerable attention from the media as a result. A startup company was funded based on one of these technologies. It may or may not succeed, but the point is that this particular line of work is now expanding beyond the bounds of research groups funded by the SENS Research Foundation, and attracting a growing level of attention. There is increasing interest in the scientific community in this strategy for treating aging. Also in 2015 another startup was founded, Human Rejuvenation Technologies, with the aim of producing a therapy for atherosclerosis based on the results of SENS Research Foundation programs for clearance of intracellular aggregates. Further, methods of repairing mitochondrial DNA damage funded in part by the SENS Research Foundation have moved beyond the laboratory and have been under commercial development since 2013 for narrow uses in the treatment of inherited mitochondrial disorders such as Leber's hereditary optic neuropathy - but the resulting technologies will be applicable to aging.

Unfortunately other lines of SENS research have yet to reach this point of critical mass: for example clearance of cross-links does see some interest and research in the broader scientific community, but has not yet had its breakthrough moment.

The Role of the Rest of the Research Community

It is not unreasonable to expect the broader research community - motivated as it is to seek cures for specific named diseases - to slowly fill in the gaps in SENS as time moves on and as the path ahead is better illuminated. For example, Alzheimer's researchers are working on immune therapies to address both amyloid plaques and other forms of junk material suspected to cause neurodegeneration. Further, some groups with no direct affiliation to the SENS Research Foundation are attempting to develop repair techniques for damaged mitochondrial DNA, build cross-link breaking drugs, or clear less well known forms of amyloid in order to treat certain classes of age-related illness.

It is also the case that regenerative medicine is a large and well funded field largely focused on using existing biological mechanisms to build new, replacement tissue for the body. Other researchers are also investigating the manipulation of telomeres in order to prevent or treat cancer. Yet more groups are working on compounds to break down accumulated biochemical junk outside cells.

Making gains in SENS research by way of unrelated bits and pieces is likely to be a slow path for progress towards meaningful extension of healthy life, however. Curing any one age-related condition is a wonderful thing for sufferers, but it will not increase healthy life span for anyone else - nor will it lead directly to therapies that can extend life without further investment and work. All of SENS must be implemented in order to reliably extend healthy life for all of us, and thus there must be at least some portion of the research community working directly and deliberately towards a complete implementation of the SENS vision.

The Ethics of a Cure for Aging

In many ways the hardest part of the path ahead for supporters of healthy life extension lies in convincing people that SENS and similar scientific projects should be funded in the first place. The science is much more certain than the public support. This is a strange state of affairs when you stop to look at it. As Aubrey de Grey notes: "Aging really is barbaric. It shouldn't be allowed. I don't need an ethical argument. I don't need any argument. It's visceral. To let people die is bad. I work to cure aging, and I think you should too, because I feel that saving lives is the most valuable thing anyone can spend their time doing, and since over 100,000 people die every single day of causes that young people essentially never die of, you'll save more lives by helping to cure aging than in any other way."

Many people demonstrate a certain willful blindness to the death and suffering caused by aging, a blindness that is not present for age-related disease like cancer or Alzheimer's. Yet if you support medical research to cure disease, prevent death, and relieve suffering, then you should also support medical research to prevent and rejuvenate age-related degeneration. How is suffering and death caused by the general deterioration of aging any different from suffering and death caused by a specific age-related condition we understand and have given a name?

We should all do our part to help speed development of therapies for aging. It is the right thing to do.

Last updated: September 28th 2015.


Man, all of this is so interesting and seemingly plausible. I support you all the way and hope you guy's defeat aging. I think we should worry about the "ethics" about curing aging after we've done it. My guess is that many people will find it harder to reject such treatments when they're actually available.
Keep at it!

Posted by: 22yr old guy at December 17th, 2010 9:57 PM

Agreed. The more time we can give ourselves on this earth, the more knowledge and goodness we will be able to spread to our fellow man.

Posted by: Auburn Grad at January 12th, 2012 2:01 PM

As of this year (2012) I have decided to give 10% of my take-home pay to the SENS Foundation, every month. I know these people and they are serious and capable.

Posted by: Tristan Bettencourt at February 11th, 2012 9:46 PM

I think this is a great idea but the world population is already growing because we are reaching ages upto 65 and 90 as opposed to 30 one hundred years ago so more people are living therefore the world population is increasing so wouldnt we fill the world?because there is only about 40% of land and we are covering about 14% already so the world may end up too small.What about the mind as well? if we live for longer than expected then wont we fill up the memory capacity?because people that are aged 90 are already finding it hard to store more information like a when a memory unit is full so wouldnt our brains have to get bigger?If that was to happen then our heads would have to get bigger but what about the rest of our body?if we can live upto 1000 years old then wouldnt our bodies have to adjust to all this becuase if that is the case then we could end up giants

Posted by: unknown at June 28th, 2012 11:56 AM

I believe that we need to look at the world affairs and humanity. Historically, the only way we generate prosperity is through WARS and BOONDOGGLE’S projects of the 30’s and 40’s.

To justify longevity and the impact on the environment and mother EARTH, we need to develop a space station habitation industry that will take us out into SPACE and start mining other planets, asteroids and satisfy the next stage of life.....Universe Exploration.

That said, we need to develop the longevity so that humans can live great lengths of time, aquire great wisdome and create great new realities for human evolution.

We will probably evolve to semi bionic stages with a core biology that holds the “soul” that sits in the center of fantastic robotics. Then eventually evolve out of our bodies altogether
to a fully biologically independent entity of pure psychic energy.

So let’s get going....can we do anything to evolve our scarcity conscientiousness to abundance conscientiousness in the near future? That could make us look after all humans and create bliss and joy for all....

I think I can feel my amyloid plaques untangling and prtoeins unfolding.... :)

Posted by: Charles Le Fevre at July 1st, 2012 12:48 PM

I suggest: biophotons, junk dna, epigenetics, cell phenotypes, gene and protein expression (what is considred ideal and not ideal? normal, and abnormal?), as areas to consider more research.

Posted by: josh at November 14th, 2012 8:27 AM

All of this may extend life but defeat our existence.... In fact we shd lead a healthy life and die ASAP after that say around 60-70 at best .....Successful mutation and progressive gene transmission (obviously to a new (child)and a healthy body)is the only natural way to extend "life" healthily if we define life extension as survival of the "genes" rather than survival of "one individual with their body"



Posted by: dnyanesh at November 17th, 2012 11:15 PM

What is the max limit brain capacity (ex: memory )?

Posted by: Andy at August 2nd, 2014 4:39 AM

I would point out that as societies age, or rather as they have a reduction in the number of young men, they become less warlike. So having more healthy and WORKING older people will probably reduce war.

On different not, where can I read more about this issue?
"4) Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions that degrade their effectiveness. Scientists can search for suitable enzymes or compounds to break down problem proteins that the body cannot handle."

Thanks, Ben

Posted by: Ben at December 19th, 2014 11:23 AM

No religious ethical question in scine. Science has its own path way .No blind belief and dogmatism.Science is to find truth. --- dr prasannakumar K

Posted by: prasanna at August 17th, 2015 10:48 AM

let us all join together and find a cure for this process called aging before we are all it now thank you hasan

Posted by: hasan... at March 14th, 2016 9:43 AM

Longevity as a target has to be a desirable goal for humanity. Society is so challenging that by the time we figure it out, and have done our bit raising families, we're often too frail or worn out to add our gained experience to the general improvement of the human condition. I read something many years ago suggesting that old testament (genesis) reported life spans were probably realistic but that the environment and life style since is probably contributing to the 'Aging damage' you talk about. Is that possible?

Posted by: Paul Bird at January 13th, 2018 4:26 PM
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