The Mainstream View of Longevity Science: Drug Discovery to Slightly Slow Aging

As the paper linked here illustrates, pharmacology remains the main focus for that part of the research community interested in intervening in the aging process. Those involved understand that this progress is very slow and very expensive while any near-future drug therapies will be marginal and come with potentially hazardous side-effects: this is a matter of trying to safely adjusting the enormously complex and still poorly understood operation of metabolism to limp along a little better when damaged by aging, or slightly slow down the pace of damage accumulation. The future that I predict is that this approach to research will continue to swallow enormous sums of money and generate nothing of any real value in terms of treatments for aging, and that this state of affairs will last until periodic damage repair approaches like SENS consistently demonstrate far better and far cheaper results in animal studies and clinical trials. There is a great deal of cultural and regulatory inertia driving the relentless focus on old-style pharmacology in medicine, regardless of its actual fit for any given situation.

Aging can be defined as the progressive decline in tissue and organismal function and the ability to respond to stress that occurs in association with homeostatic failure and the accumulation of molecular damage. Aging is the biggest risk factor for human disease and results in a wide range of aging pathologies. Although we do not completely understand the underlying molecular basis that drives the aging process, we have gained exceptional insights into the plasticity of life span and healthspan from the use of model organisms such as the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene mutations in key cellular pathways that regulate environmental sensing, and the response to stress, have been identified that prolong life span across evolution from yeast to mammals. These genetic manipulations also correlate with a delay in the onset of tissue and organismal dysfunction.

While the molecular genetics of aging will remain a prosperous and attractive area of research in biogerontology, we are moving towards an era defined by the search for therapeutic drugs that promote healthy aging. Translational biogerontology will require incorporation of both therapeutic and pharmacological concepts. The use of model organisms will remain central to the quest for drug discovery, but as we uncover molecular processes regulated by repurposed drugs and polypharmacy, studies of pharmacodynamics and pharmacokinetics, drug-drug interactions, drug toxicity, and therapeutic index will slowly become more prevalent in aging research. As we move from genetics to pharmacology and therapeutics, studies will not only require demonstration of life span extension and an underlying molecular mechanism, but also the translational relevance for human health and disease prevention.

Link: http://dx.doi.org/10.1016/bs.adgen.2015.06.002

Comments

I think part of it has to do with the repair approach being viewed as "not real science" or fringe science, since a lot of people seem to think that they need to understand entirely how something works before trying to intervene. I don't see this standard approach changing unless it's the big pharma companies themselves leading the change. As you said, the cultural and regulatory view on medicine has been the same for a while now, and a lot of people have a lot invested into the system in its current state. Maybe once true rejuvenation is shown to be possible and repeatable, the approach will begin to change. There is potential to hit a home run as far as profits go if there is a successful aging treatment, so it's somewhat surprising that more companies aren't approaching things from multiple angles.

I don't see how something that only modestly slows down aging would be successfully tested in a clinical trial, unless it was done over the course of 20+ years either. And that's a long enough time that many people can't afford to spend waiting.

Posted by: Ham at September 4th, 2015 7:50 AM

Again, I agree 100%. I don't know if anyone of you is aware of the latest Singularity podcast with Liz Parrish, the CEO of BioViva.

https://www.singularityweblog.com/bioviva-ceo-liz-parrish-on-gene-therapy/

It was great listening to her because she has a clear opinion on what is going wrong. If terminally ill patients are denied access to experimental drugs, unless they or their doctors have great connections, then chances to try anti-aging drugs anytime soon are next to nil. This is why she went abroad and keeps doing what she does. I wish we had more people like her.

Posted by: Waverunner at September 7th, 2015 6:26 AM

Liz is amazing and really sees just how broken the current FDA system is. I know she is working hard to drive down the cost of therapy too which is good news.

Posted by: Steve H at September 7th, 2015 11:48 AM

Yes, she truly is amazing. Gene therapy holds the potential not only to cure many diseases but also to do so at minimal cost. All the best to her.

Posted by: Waverunner at September 8th, 2015 12:52 AM

Thing with Liz is she wants to push into testing in people now, not mice, people. Her approach in some ways is SENS like (some of her targets are anyway) but she is also testing transient telomerase induction. The for and against arguments have raged for ten years or more so I figure she took the Michael Fossel route, we dont know lets get the data.I see Bill Andrews and Aubrey both are quoted as supporting her work on the BV website, good to see ADG is supportive even if the methods are not full SENS.

Gene therapy is very expensive at the moment using AAV but Bioviva has invested in technology that apparently will drive the cost down and is looking at other ways to make it cheaper.

Posted by: Steve H at September 8th, 2015 2:23 AM

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