In the last year or so, we have seen remarkable progress with a number of interventions that target the aging processes to prevent and treat age-related diseases, however, we should always remain grounded when it comes to scientific progress. We should avoid the dangers of being both too optimistic but also too pessimistic about the potential of rejuvenation biotechnology.

Senescent cell clearance has enjoyed lots of media attention and is entering human clinical trials later this year with Unity Biotechnology. We have LysoCLEAR from Ichor Therapeutics moving towards the clinic with a therapy based on the LysoSENS approach, which is advocated for by the SENS Research Foundation and seeks to treat age-related blindness caused by the accumulation of waste products in the retina cells of patients. Dr. David Sinclair is moving into human trials this year with a therapy aimed at repairing DNA damage, one of the main reasons we are thought to age.

We have had amazing progress in immunotherapy, in which the immune system is taught to detect cancer and other diseases far more efficiently. For instance, immunotherapy has been used to allow the immune system to spot cancer that uses the same “Do not eat me” signals that healthy cells use to avoid destruction.

We even had a startling result in another immunotherapy trial in which the hair of patients turned from grey back to its original colour[1]. It is thought to be the result of the immune system reducing the pro-inflammatory signals that block stem cell activity and tissue maintenance. This may also potentially happen if we clear out senescent cells – mouse experiments hint that this may be the case.

Source: Rivera, N., Boada, A., Bielsa, M. I., Fernández-Figueras, M. T., Carcereny, E., Moran, M. T., & Ferrándiz, C. (2017). Hair Repigmentation During Immunotherapy Treatment With an Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Agent for Lung Cancer. JAMA dermatology.







This is one of the most promising areas of research, as it could potentially see us eradicate serious diseases, including cancer and HIV/AIDS.

There is plenty to be excited about, and with all this recent good news, it is tempting to become overly optimistic. We have seen a significant number of people suggest that everything will be fine now, because the first technologies are starting to arrive in the repair-based approach to aging, but this is a dangerous mindset to fall into. Restoring hair pigmentation is great, but looking at this picture, we should not think we are close to bringing the aging processes under medical control.

Sidestepping the complexity

The metabolism of the human body is a highly complex interconnected machine, and anyone with an understanding of biology understands that controlling this complexity is likely the work of decades, if not longer. However, there is an approach that seeks to sidestep this complexity: rejuvenation biotechnology.

Rejuvenation biotechnology is a multi-disciplinary field of science whose aim is the prevention and reversal of age-related diseases by targeting the aging processes that cause them.







This is a dramatic deviation from traditional medicine and, in particular, geriatrics, which aims to treat the consequences – often by attempting to tweak metabolism far downstream from the actual root causes – rather than prevent them from happening in the first place by focusing on where the damage begins. This traditional approach of treating the symptoms and not the cause is an approach doomed to fail, and considering people continue to die from age-related diseases, it is time to admit that this approach has been a spectacular failure.

Repairing the underlying damage, while not a trivial task, is considerably less complex than attempting to tweak metabolism or treating the consequences as traditional geriatrics does.

Whether you categorize the damages of aging through the seven-damages model of SENS or the Hallmarks of Aging model, they are much the same, and both advocate for the damage-repair approach to aging, which is becoming a realistic goal in the next couple of decades.

We should be optimistic but not complacent

This is indeed good news and a testament to the hard work and dedication of the pioneers of damage repair, such as Dr. Aubrey de Grey, who have spent many years working to advance the progress of rejuvenation biotechnology.







Some parts of the damage repair approach are now far advanced and enjoying a great deal of attention and hype in the media, but there are a number of approaches to damage that are yet to reach this level of attention.

Because aging is comprised of a number of interlinked but distinct processes, addressing only one or two of them is unlikely to yield significant increases in healthy lifespan. This is confirmed in rodent experiments in which a single damage has been addressed. In these experiments, we often see some increase in lifespan, for instance when reversing epigenetic alterations in mice late last year [2] and in the senescent cell removal experiments in recent years [3-4].

We see increased lifespans as a result of addressing these hallmarks of aging and a delay of age-related diseases, which is the aim of rejuvenation biotechnology. Yet, these animals ultimately still die of the age-related damages that are not being addressed.

This is because the repair-based approach relies on comprehensive intervention against all the damage types, not just one. Believing that addressing one will make a dramatic difference puts us in serious danger of becoming overly optimistic and thus complacent. Quite simply, there are no magic bullets.

So what is the solution?







At the risk of stating the completely obvious, we should be focusing the greatest efforts now on the areas where progress is the least advanced. We need to help the approaches that are lagging behind catch up with the rest that are more advanced.

Crosslink breaking, mitochondrial gene transfer, and the destruction of misfolded proteins are all areas that are in need of support. We recently looked at the current state of progress here to give you a good idea of the problem areas.

So, why are they lagging behind in the first place? Well, this is because they are, generally speaking, more technically difficult, and they require greater efforts to research and develop. They are lagging behind because these are pioneering studies, which are not something business and investors are generally interested in funding – until there is a product on the horizon, of course. We talk about this and the other bottlenecks to research progress in another article.

As it stands, a significant number of critical research areas that are needed to realize full medical control of the aging processes to address age-related diseases are yet to reach a proof-of-concept stage. That leaves the basic science and early-stage development of these technologies entirely in the hands of philanthropy.

Conclusion







Look at the guy who got his hair pigmentation back. Isn’t it fascinating? It truly is. Perhaps it is not just his hair that improved, but also skin and some other tissues. However, why did he and other people whose hair look better now have to undergo the treatment in the first place? Because their DNA was damaged by the mechanisms of aging, and there was no way to prevent this, because the rejuvenation therapies to protect us from this damage are not here yet.

If you want them be developed sooner, consider this.

Governments are not funding aging studies sufficiently, because they believe the rejuvenation approach is too radical (this is a simplification, but still it is the main reason). Business is not supporting these studies enough, because they are basic-science, early-stage endeavors, with no final product that can be sold to make revenue. Who is left? What other source is out there? Only the general public, and if the general public is not well-informed and supportive, then what source is left? Only the community promoting rejuvenation technologies. Yes, including you.

We at LEAF/Lifespan.io are not believers anymore. We are not waiting for a miracle to save us all from the diseases of old age. Instead, we are creating this miracle with our own hands. And, if more people take this step from ungrounded beliefs to a critical assessment of the situation, and stand by us, we will be able to achieve more.

Literature







[1] Rivera, N., Boada, A., Bielsa, M. I., Fernández-Figueras, M. T., Carcereny, E., Moran, M. T., & Ferrándiz, C. (2017). Hair Repigmentation During Immunotherapy Treatment With an Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Agent for Lung Cancer. JAMA dermatology.

[2] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.

[3] Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B., … & Van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232.

[4] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.