Today, we want to highlight the Longevity Dialogues, a new series from Seeking Delphi, which is hosted by futurist Mark Sackler and features various notable figures in the aging research and futurist community. Its first episode, which was recently broadcast, featured Sergey Young, David Wood, and Jose Cordeiro.
This episode focuses on a possible scenario in which therapies that address the human aging processes have been developed in the mid to late 2030s, making us capable of adding decades to healthy lifespan.
Clearly, this is currently a purely hypothetical situation, but it can nonetheless be a fun and thought-provoking use of time. It is also a valuable exercise to consider likely future scenarios now along with the potential challenges and opportunities that such futures may offer.
The panelists mention some of the therapies that they think will be available then, and we will join the discussion by speculating a little about what types of therapies might be available to people in the 2030s based on our own knowledge of the field.
What kinds of therapies might we have by then?
A lot can change in just 15 years, especially given the accelerating pace that aging research is currently enjoyingy. These are the top therapies that we think will arrive by the mid 2030s and that directly address the aging processes and repair their associated damage. Before this, it is likely that there will be a number of other therapies that address smaller parts of the aging processes, such as drugs that optimize metabolism, and while they may increase healthspan or even modestly increase lifespan, they are not, in our opinion, the true game-changers.
Senolytics are drugs that purge the body of harmful senescent cells, which are non-dividing damaged cells that secrete inflammatory signals, in order to encourage youthful tissue regeneration. Senescent cell accumulation is one of the reasons we age.
There are currently a number of ongoing human trials of senolytics, and, sooner or later, it seems likely that the results seen in animal studies will be translated to people.
While the recent failure of Unity Biotechnology to translate UBX0101, a senolytic drug targeting p53, into humans is a disappointment, other approaches may yet succeed. Given that we are only seeing the first generation of senolytics reaching the clinic and our understanding of the heterogeneity of senescent cells is still growing, it seems likely that the second generation of senolytics will be considerably more refined and more likely to succeed.
With that in mind, it seems plausible that by the 2030s, senolytics will be one of the therapies available for delaying aging and supporting longer, healthier lifespans.
Telomerase gene therapy
Telomere attrition is thought to be a reason we age and is the gradual loss of the protective caps of our chromosomes. Telomere attrition limits the number of times our cells can divide, slowly leading to dwindling populations of cells in vital organs.
Telomerase gene therapy has yet to reach the point of being tested in humans and entering clinical trials, but with over a decade of steady research and progress by pioneers such as Dr. Maria Blasco at the CNIO in Spain, we believe that by the mid 2030s, this also has a good chance of being in regular human use.
Most likely, the therapy will be initially used to address telomere biology diseases, such as dyskeratosis congenita, aplastic anemia, myelodysplasia, acute myeloid leukemia, and idiopathic pulmonary fibrosis. From this point, wider use of the therapy is likely to begin, as support grows for targeting the aging processes directly in order to prevent age-related diseases.
Therapeutic plasma exchange
Pioneering Drs. Irina and Mike Conboy have been researching blood factors and their role in aging for over twenty years. During that time, they have isolated a number of key factors in aged blood that appear to regulate aging.
In young people, these factors are typically present in far lower amounts and often play a beneficial role in metabolism and cellular behavior; however, during aging, their levels rise, and they switch from being useful to becoming pro-aging in nature, preventing stem cells from working and tissue from regenerating.
The Conboys have demonstrated in animal studies that it is possible to filter and calibrate aged blood so that these pro-aging factors are reduced to youthful levels again, and this spurs regeneration of tissues. To take this to human trials, the use of therapeutic plasma exchange has been proposed. The calibration of pro-aging blood factors addresses altered intercellular communication, the breakdown of how cells communicate with each other via the bloodstream, and is thought to be a reason we age.
Therapeutic plasma exchange is a 30-year-old clinical procedure that is currently used to treat a number of rare diseases, primarily autoimmune disorders, but it has more recently found increasing interest in the context of age-related diseases. Given that therapeutic plasma exchange is already an approved therapy and that modifying it to address aging will only require some adaptation of the approach, we think that this has a very good chance of being a common therapy by the mid 2030s.
Partial cellular reprogramming
Perhaps the most distant in likelihood of being in common use by the mid 2030s is partial cellular reprogramming. This approach sees cells transiently exposed to reprogramming factors, commonly known as the Yamanaka factors, that reset the epigenetic age of the cell to reverse cellular aging.
Full reprogramming of cells has been in use for over a decade and is the basis of iPSC stem cell therapy, in which cells from a patient are taken, exposed to reprogramming factors in a dish to revert them to a developmental state. This allows them to become any other type of cell in the body, much as embryonic stem cells can. These cells are then guided into becoming a desired cell type and multiplied in their millions before being returned to the patient. When cells are reprogrammed, it also resets their cellular age.
Partial cellular reprogramming relies on exposing the cells just long enough to reset their age but not causing them to forget their type, which is good because the aim of partial cellular reprogramming is to achieve this while the cells are in a living person. The approach has already been successfully demonstrated to work in living animals, but there will be a lot of work to do before this approach reaches humans.
More episodes are in the works
The next installment of Longevity Dialogues is anticipated for mid-November and will feature Lifespan.io President Keith Comito, Dr. Aubrey de Grey, and Dr. Nir Barzilai, who will be discussing Selling the Science of longevity.
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Mark J Sackler
October 30, 2020
Thanks for sharing this, Steve.
As for the therapies that might be available 15-20 years from now, that aspect of the podcast was simply intended to set the scene for a specific scenario within which we could discuss other issue. That said, implementation was one issue discussed that very much will be dependent on the therapies. I personally felt that the range of therapies required would be much broader than were discussed…more along the lines of what you have written here.
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