Unity Biotechnology – The Rational Argumentator

What It Will Be Like to Be an 85-Year-Old in the 2070s – Article by Scott Emptage

June 9, 2018 Scott Emptage Comments 0 Comment

Scott Emptage

I will be 85 sometime in the early 2070s. It seems like a mirage, an impossible thing, but the future eventually arrives regardless of whatever you or I might think about it. We all have a vision of what it is to be 85 today, informed by our interactions with elder family members, if nothing else. People at that age are greatly impacted by aging. They falter, their minds are often slowed. They are physically weak, in need of aid. Perhaps that is why we find it hard to put ourselves into that position; it isn’t a pleasant topic to think about. Four decades out into the future may as well be a science-fiction novel, a faraway land, a tale told to children, for all the influence it has on our present considerations. There is no weight to it.

When I am 85, there will have been next to no senescent cells in my body for going on thirty years. I bear only a small fraction of the inflammatory burden of older people of past generations. I paid for the products of companies descended from Oisin Biotechnologies and Unity Biotechnology, every few years wiping away the accumulation of senescent cells, each new approach more effective than the last. Eventually, I took one of the permanent gene therapy options, made possible by biochemical discrimination between short-term beneficial senescence and long-term harmful senescence, and then there was little need for ongoing treatments. Artificial DNA machinery floats in every cell, a backup for the normal mechanisms of apoptosis, triggered by lingering senescence.

When I am 85, the senolytic DNA machinery will be far from the only addition to my cells. I underwent a half dozen gene therapies over the years. I picked the most useful of the many more that were available, starting once the price fell into the affordable-but-painful range, after the initial frenzy of high-cost treatments subsided into business as usual. My cholesterol transport system is enhanced to attack atherosclerotic lesions, my muscle maintenance and neurogenesis operate at levels far above what was once a normal range for my age, and my mitochondria are both enhanced in operation and well-protected against damage by additional copies of mitochondrial genes backed up elsewhere in the cell. Some of these additions were rendered moot by later advances in medicine, but they get the job done.

When I am 85, my thymus will be as active as that of a 10-year-old child. Gene and cell therapies were applied over the past few decades, and as a result my immune system is well-gardened, in good shape. A combination of replacement hematopoietic stem cells, applied once a decade, the enhanced thymus, and periodic targeted destruction of problem immune cells keeps at bay most of the age-related decline in immune function, most of the growth in inflammation. The downside is that age-related autoimmunity has now become a whole lot more complex when it does occur, but even that can be dealt with by destroying and recreating the immune system. By the 2030s this was a day-long procedure with little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis will be curable, preventable, and reversible, and that will have been the case for a few decades. There are five or six different viable approaches in the marketplace, all of which basically work. I used several of their predecessors back in the day, as well. Most people in the wealthier parts of the world have arteries nearly free from the buildup of fat and calcification. Cardiovascular disease with age now has a very different character, focused more failure of tissue maintenance and muscle strength and the remaining small portions of hypertension that are still problematic for some individuals. But that too can be effectively postponed through a variety of regenerative therapies.

When I am 85, there will be an insignificant level of cross-linking in most of my tissues, as was the case since my early 60s. My skin has the old-young look of someone who went a fair way down the path before being rescued. Not that I care much about that – I’m much more interested in the state of my blood vessels, the degree to which they are stiff and dysfunctional. That is why removal of cross-links is valuable. That is the reason to keep on taking the yearly treatments of cross-link breakers, or undergo one of the permanent gene therapies to have your cells produce protective enzymes as needed.

When I am 85, I will have a three-decade patchwork history of treatments to partially clear this form of amyloid or that component of lipofuscin. I will not suffer Alzheimer’s disease. I will not suffer any of the common forms of amyloidosis. They are controlled. There is such a breadth of molecular waste, however: while the important ones are addressed, plenty more remain. This is one of the continuing serious impacts to the health of older individuals, and a highly active area of research and development.

When I am 85, I will be the experienced veteran of several potentially serious incidences of cancer, all of which were identified early and eradicated by a targeted therapy that produced minimal side-effects. The therapies evolve rapidly over the years: a bewildering range of hyper-efficient immunotherapies, as well as treatments that sabotage telomere lengthening or other commonalities shared by all cancer cells. They were outpatient procedures, simple and quick, with a few follow-up visits, so routine that they obscured the point that I would be dead several times over without them. The individual rejuvenation technologies I availed myself of over the years were narrowly focused, not perfect, and not available as early as I would have liked. Cancer is an inevitable side-effect of decades of a mix of greater tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be in the 2050s? No. It is next to impossible to say how the differences noted above will perform in the real world. They are all on the near horizon, however. The major causes of age-related death today will be largely controlled and cured in the 2050s, at least for those in wealthier regions. If you are in your 40s today, and fortunate enough to live in one of those wealthier region, then it is a given that you will not die from Alzheimer’s disease. You will not suffer from other common age-related amyloidosis conditions. Atherosclerosis will be reliably controlled before it might kill you. Inflammatory conditions of aging will be a shadow of what they once were, because of senolytic therapies presently under development. Your immune system will be restored and bolstered. The stem cells in at least your bone marrow and muscles will be periodically augmented. The cross-links that cause stiffening of tissues will be removed. Scores of other issues in aging process, both large and small, will have useful solutions available in the broader medical marketplace. We will all live longer and in better health as a result, but no-one will be able to say for just how long until this all is tried.

Scott Emptage is an anti-aging activist in the United Kingdom.

UNITY Biotechnology Raises $116M for Senescent Cell Clearance Development – Article by Reason

October 31, 2016 Reason Comments 1 comment

Reason

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The whispers of late have had it that UNITY Biotechnology was out raising a large round of venture funding, and their latest press release shows that this was indeed the case. The company, as you might recall, is arguably the more mainstream of the current batch of startups targeting the clearance of senescent cells as a rejuvenation therapy. The others include Oisin Biotechnologies, SIWA Therapeutics, and Everon Biosciences, all with different technical approaches to the challenge. UNITY Biotechnology is characterized by a set of high profile relationships with noted laboratories, venture groups, and big names in the field, and, based on the deals they are doing, appear to be focused on building a fairly standard drug development pipeline: repurposing of apoptosis-inducing drug candidates from the cancer research community to clear senescent cells, something that is being demonstrated with various drug classes by a range of research groups of late. Senescent cells are primed to apoptosis, so a nudge in that direction provided to all cells in the body will have little to no effect on normal cells, but tip a fair proportion of senescent cells into self-destruction. Thus the UNITY Biotechnology principals might be said to be following the standard playbook to build the profile of a hot new drug company chasing a hot new opportunity, and clearly they are doing it fairly well so far.

UNITY Biotechnology Announces $116 Million Series B Financing

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UNITY Biotechnology, Inc. (“UNITY”), a privately held biotechnology company creating therapeutics that prevent, halt, or reverse numerous diseases of aging, today announced the closing of a $116 million Series B financing. The UNITY Series B financing ranks among the largest private financings in biotech history and features new investments from longtime life science investors ARCH Venture Partners, Baillie Gifford, Fidelity Management and Research Company, Partner Fund Management, and Venrock. Other investors include Bezos Expeditions (the investment vehicle of Jeff Bezos) and existing investors WuXi PharmaTech and Mayo Clinic Ventures. Proceeds from this financing will be used to expand ongoing research programs in cellular senescence and advance the first preclinical programs into human trials.

The financing announcement follows the publication of research that further demonstrates the central role of senescent cells in disease. The paper, written by UNITY co-founders Judith Campisi and Jan van Deursen and published today, describes the central role of senescent cells in atherosclerotic disease and demonstrates that the selective elimination of senescent cells holds the promise of treating atherosclerosis in humans. In animal models of both early and late disease, the authors show that selective elimination of senescent cells inhibits the growth of atherosclerotic plaque, reduces inflammation, and alters the structural characteristics of plaque such that higher-risk “unstable” lesions take on the structural features of lower-risk “stable” lesions. “This newly published work adds to the growing body of evidence supporting the role of cellular senescence in aging and demonstrates that the selective elimination of senescent cells is a promising therapeutic paradigm to treat diseases of aging and extend healthspan. We believe that we have line of sight to slow, halt, or even reverse numerous diseases of aging, and we look forward to starting clinical trials with our first drug candidates in the near future.”

So this, I think, bodes very well for the next few years of rejuvenation research. It indicates that at least some of the biotechnology venture community understands the likely true size of the market for rejuvenation therapies, meaning every human being much over the age of 30. It also demonstrates that there is a lot of for-profit money out there for people with credible paths to therapies to treat the causes of aging. It remains frustrating, of course, that it is very challenging to raise sufficient non-profit funds to push existing research in progress to the point at which companies can launch. This is a problem throughout the medical research and development community, but it is especially pronrounced when it comes to aging. The SENS view of damage repair, which has long incorporated senescent cell clearance, is an even tinier and harder sell within the aging research portfolio – but one has to hope that funding events like this will go some way to turn that around.

From the perspective of being an investor in Oisin Biotechnologies, I have to say that this large and very visible flag planted out there by the UNITY team is very welcome. The Oisin team should be able to write their own ticket for their next round of fundraising, given that the gene therapy technology they are working on has every appearance of being a superior option in comparison to the use of apoptosis-inducing drugs: more powerful, more configurable, and more adaptable. When you are competing in a new marketplace, there is no such thing as too much validation. The existence of well-regarded, well-funded competitors is just about the best sort of validation possible. Well-funded competitors who put out peer-reviewed studies on a regular basis to show that the high-level approach you and they are both taking works really well is just icing on the cake. Everyone should have it so easy. So let the games commence! Competition always drives faster progress. Whether or not I had skin in this game, it would still be exciting news. The development of rejuvenation therapies is a game in which we all win together, when new treatments come to the clinic, or we all lose together, because that doesn’t happen fast enough. We can and should all of us be cheering on all of the competitors in this race. The quality and availability of the outcome is all that really matters in the long term. Money comes and goes, but life and health is something to be taken much more seriously.

Now with all of that said, one interesting item to ponder in connection to this round of funding for UNITY is the degree to which it reflects the prospects for cancer therapies rather than the prospects for rejuvenation in the eyes of the funding organizations. In other words, am I being overly optimistic in reading this as a greater understanding of the potential for rejuvenation research in the eyes of the venture community? It might be the case that the portions of the venture community involved here understand the market for working cancer drugs pretty well, and consider that worth investing in, with the possibility of human rejuvenation as an added bonus, but not one that is valued appropriately in their minds. Consider that UNITY Biotechnology has partnered with a noted cancer therapeutics company, and that the use of drugs to inducing apoptosis is a fairly well established approach to building cancer treatments. That is in fact why there even exists a range of apoptosis-inducing drugs and drug candidates for those interested in building senescent cell clearance therapies to pick through. Further, the presence of large numbers of senescent cells does in fact drive cancer, and modulating their effects (or removing them) to temper cancer progress is a topic under exploration in the cancer research community. So a wager on a new vision, or a wager on the present market? It is something to think about.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.

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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

25% Median Life Extension in Mice via Senescent Cell Clearance, Unity Biotechnology Founded to Develop Therapies – Article by Reason

February 3, 2016 Reason Comments 0 Comment

Reason

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With today’s news, it certainly seems that senescent cell clearance has come of age as an approach to treating aging and age-related conditions. Some of the leading folk in the cellular senescence research community today published the results from a very encouraging life span study, extending life in mice via a method of removing senescent cells. This is much the same approach employed in one of the first tests of senescent cell clearance, carried out in accelerated aging mice a few years ago, but in this case normal mice were used, leaving no room to doubt the relevance of the results. The researchers have founded a new company, Unity Biotechnology, to develop therapies for the clinic based on this technology. Clearance of senescent cells has been advocated as a part of the SENS vision for the medical control of aging for more than a decade now, and it is very encouraging to see the research and development community at last coming round to this view and making tangible progress.

Senescent cells have removed themselves from the cycle of replication in reaction to cell and tissue damage, or a local tissue environment that seems likely to result in cancer. Their numbers accumulate with age. Most are destroyed by the immune system or their own programmed cell death mechanisms, but enough linger for the long term for their growing presence to be one of the contributing causes of the aging process. These cells behave badly, secreting harmful signals that degrade tissue function, generate inflammation, and alter the behavior of surrounding cells as well. Near every common age-related condition is accelerated and made worse by the presence of large numbers of senescent cells. We would be better off without them, aging would be slowed by the regular removal of these errant cells, and the therapies to make that possible are on the near horizon.

The mouse lifespan study is the important news here, as it demonstrates meaningful extension of median life span through removal of senescent cells, the first such study carried out in normal mice for this SENS-style rejuvenation technology. This sort of very direct and easily understood result has a way of waking up far more of the public than the other very convincing evidence of past years. So it looks like Oisin Biotechnology, seed funded last year by the Methuselah Foundation and SENS Research Foundation to bring a senescent cell clearance therapy to market, now has earnest competition. Insofar as the competitive urge in business and biotechnology speeds progress and produces better results, let the games begin, I say.

Scientists Can Now Radically Expand the Lifespan of Mice – and Humans May Be Next

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Researchers have made this decade’s biggest breakthrough in understanding the complex world of physical aging. The researchers found that systematically removing a category of living, stagnant cells (ones which can no longer reproduce) extends the lives of otherwise normal mice by 25 percent. Better yet, scouring these cells actually pushed back the process of aging, slowing the onset of various age-related illnesses like cataracts, heart and kidney deterioration, and even tumor formation. “It’s not just that we’re making these mice live longer; they’re actually stay healthier longer too. That’s important, because if you were going to equate this to people, well, you don’t want to just extend the years of life that people are miserable or hospitalized.” By rewriting a tiny portion of the mouse genetic code, the team developed a genetic line of mice with cells that could, under the right circumstances, produce a powerful protein called caspase when they start secreting p16. Caspase acts essentially as a self-destruct button; when it’s manufactured in a cell, that cell rapidly dies. So what exactly are these circumstances where the p16 secreting cells start to create caspase and self-destruct? Well, only in the presence of a specific medicine the scientists could give the mice. With their highly-specific genetic tweak, the scientists had created a drug-initiated killswitch for senescent cells. In today’s paper, the team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells.

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

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Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

Unity Biotechnology Launches with a Focus on Preventing and Reversing Diseases of Aging

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Unity will initially focus on cellular senescence, a biological mechanism theorized to be a key driver of many age-related diseases, including osteoarthritis, glaucoma and atherosclerosis. “Imagine drugs that could prevent, maybe even cure, arthritis or heart disease or loss of eyesight. It’s an incredible aspiration. If we can translate this biology into medicines, our children might grow up in significantly better health as they age. There will be many obstacles to overcome, but our team is committed and inspired to achieve our mission. This has been a long journey, and we’re at the point now where we can start making medicines to achieve in humans what we’ve achieved in mice. I can’t wait to see what happens as we move into the clinic.”

To close this post, and once again, I think it well worth remembering that SENS rejuvenation biotechnology advocates and supporters have been calling for exactly this approach to treating aging for more than a decade. That call was made based on the evidence arising from many fields of medical research, and from a considered perspective of aging as a process of damage accumulation, one that can be most effectively treated by repair of that damage. The presence of senescent cells is a form of damage. SENS was not so long ago derided and considered out on the fringe for putting forward that position, but for several years now it has been very clear that the SENS viewpoint was right all along. I strongly encourage anyone who remains on the fence about the validity of the SENS proposals for the treatment of aging to reexamine his or her position on the science.