Complexities of Human Lifespan Extension

Many of us would like to live longer if the quality of that extended life is high. Recently, there has been a movement among biotechs and wealthy individuals trying to capitalize on the advances of genomics and modern medicine to address this topic. Anyone attempting this should read this posting.

Causing the cells of the body to behave younger is an extremely complicated task. There have been many approaches to this goal. Some individuals have taken to injections/ingestion of various plant extracts or growth hormones. However, the chances that the complex operation of cell regeneration or rejuvenation can be put into one or more small molecules is virtually nil. A small molecule cannot encode enough information to orchestrate a rejuvenation therapy. It’s simple pharmacology, each small molecule has its own profile of tissue penetration and activity which would not be suitable for all targets. A complex task like rejuvenation would require modifying dozens of systems in a coordinated, time sensitive manner all over the body.

Hormones, protein cytokines and growth signals of this nature have been used to some success with in vitro (cell culture) or in vivo (animal) models. I would like to stress here that when you put exogenous (external) sources of hormones or protein cytokines into the body, the cells and tissues are forced into a non-physiologic, unnatural state. In effect, adding extra signals into the body adds extra metabolic stresses. The stresses involved with hormone/protein cytokine use, even if minimized, will eventually unravel into a few possibilities. The first possibility is that nothing with happen, which is much better than the following. The next possibility is cancerous growth and the next is either limited tissue specific regeneration or a molecular illusion of successful regeneration. You could also get a mixture of regeneration of some tissues accompanied by cancerous growth! The status of tissue regeneration would be impossible to demonstrate with today’s technology without resorting to molecular analysis of a biopsy, making validation of this therapy highly problematic.
There are well over one hundred cell types in the body and the tissues of various organs are usually made up of several of these. It may be that a mixture of cytokines and hormones can have a limited effect on some of these cell types but a wider, homeostatic controlled “age reducing” effect would be impossible to create with one or more protein signals. Not to mention the tissue barriers that these hormones and cytokines would have to overcome to reach protected sites in the brain, eye, and reproductive tract to mention a few. Growth hormones are designed to be made in the body with specific interplay between organs and tissues. In effect, the body is constantly talking to itself and adding another voice to the mixture is a terrible idea if one doesn’t understand the context of the bodies’ internal conversation.  The difficulty with managing current hormone replacement therapies demonstrates this perfectly.

Some of the main questions in the anti-aging field are: 1) which cell systems should be modified?, and how long should the treatment last and under what controls should it persist?

Here is a list of things I would want in hand before I attempted a rejuvenation strategy. 1) An advanced understanding of why cellular processes lead to aging. 2) A method of programming genomic DNA and sending synthetic virus delivery vehicles throughout the adult human body. 3) A way of ensuring that the same cell is not treated twice with a single event treatment. 4) A non-invasive way of measuring success of the treatment. 5) Conclusive proof that the strategy works in multiple mammalian animal models.

In the end, I believe that this type of therapeutic will eventually work and Aubrey de Grey is advocating an approach which I feel the most comfortable with.  It starts with addressing specific blood accessible concerns one at a time and moving on from there.  For example, atherosclerosis or cholesterol rich plaques in artery walls are a major source of age related health decline and morbidity.  Aubrey suggests that the indigestible components of artery plaques could be digested with an engineered enzyme which would be handed to the immune cells responsible for cleaning the body.  I think it is at least possible to find such an enzyme but it will take an advanced gene delivery tool like a synthetic virus  to get the new gene(s) in place.   Especially under conditions which are permanent or time sensitive and promote immune tolerance to the foreign enzyme.  I predict that once the tools of synthetic virology have been built up to overcome the current issues of gene delivery, immunity, and cellular homeostasis, we will see great progress on the anti-aging front.

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