Or you could take the Wryss-Corey route and test rejuvenation but using plasma. Harold has a promising HPE therapy proposal which could yield useful results and the safety of regular Plasma exchange is already established. Also if rejuvenation can be demonstrated then funding would rapidly follow allowing a detailed analysis of the blood factors responsible for the rejuvenation effects.
GDF-11, Klotho, WNT, Oxytocin, FOXN1 and NAD+ all show some level of rejuvenating effect but the problem is creating or obtaining compounds capable of emulating/activating them. Plasma contains all these factors and whilst plasma infusion on a regular basis is not practical/possible there may be ways around that problem.
From: Mike Darwin To: Dr. Harold Katcher Cc: Gerontology Research Group ; steve hill Sent: Thursday, 5 March 2015, 18:49Subject: Re: [GRG] Kidney donor ages…
This is good to know. I suspect that aging is considerably more complex than pro- and anti-aging molecules circulating in the plasma, though I agree that these appear to be very powerful factors and should be pursued aggressively. I also believe that their optimum application will likely result both in significant rejuvenation and significant extension of the lifespan. Certainly it is pretty clear that the Hayflick limit and the conventional wear and tear theories of aging are, to a great extent, an artifact of programmed senescence and that understanding the mechanics of this process should be the focus of anti-aging research.
An even higher priority is to do small-scale, very-rapid-turn around research to determine the applicability of these current discoveries to humans quickly – in months to years, rather than decades. The Conboys, and others in academia, will no doubt continue to make progress in unraveling the molecular mechanics of aging and rejuvenation. However, even now, there are three putative rejuvenatory molecules whose structure is known. What should be happening now, as I write this, is that efforts should be underway on the following fronts:
1) Competent and demonstrably rapid results efforts to achieve affordable intermediate level production of these species should be underway. This could be achieved by any of several means which are not mutually exclusive, such as small scale high yield production in a de novo lab(s), contract production with existing protein production firms in the West, or contract production with protein production companies or pharmaceutical concerns in China.
2) The creation of an animal research facility capable of applying these molecules and of investigating their combination with pheresis in both rat and dog models. Dogs are almost essential for this work, because there are large populations of already old, genetically heterogenous animals readily available for experimentation. Uniquely, old dogs can be recruited from the community for clinical trials in much the same way as humans are. Additionally, there are many aged dogs available for experimentation using conventional approaches. The genetic heterogeneity of dogs, their divers environmental history and their variable breed and size “specific” aging rate make them ideal for this work. Another powerful factor favoring their use is that their size and physiology make vascular access, physiological monitoring, veterinary medical imaging and general veterinary management and care compatible with the same equipment used for these applications in humans. Additionally, there is a vast reservoir of veterinary expertise and literature in both the specific pathologies that affect this species, as well as their clinical course in normal, healthy aging. Perhaps of similar importance is that a significant fraction of aging dogs experience an AD-like brain wasting disease with a clinical course that is strikingly similar to that of humans. Dogs also experience a normal cerebral atrophy of aging which closely mirrors that seen in aging humans.
Identification of facilities to synthesize anti-aging proteins, as well as their synthesis and initial vetting for purity and activity, will likely take on the order of 12 to 18 months, under the most optimistic circumstances; with the proviso that funding for the effort is available. Similarly, the creation of purchase of an existing animal research facility with the necessary capabilities and infrastructure will require a similar period of time.
I have considered the possibility of using a contract animal research facility and rejected it for numerous reasons. First, both the general insights and the clinical details of immediate application of the research to humans will literally be lost in translation with contract facilities. These entities will have neither the interest, nor the ability to translate new research findings to humans; and the art of immediate clinical application lies in conducting the animal research with the practicality of human application always in mind and at the forefront of the design and execution of the experimental work. Second, contract work is rigidly defined, inflexible, and always at arms-length from the needs and goals of those who commissioned it. The results of such work are often useless for the ultimate purpose, or require much additional and costly research to refine and adapt for human application. What is needed is an integrated bench to bedside approach.
If these organizational and very practical efforts are not launched soon, then clinical application of these emerging insights will not be 5-7 years ahead, but rather will come decades from now which is unarguably too late for most of us here.