Articulating the Case for the Longevity Dividend

To go along with the recent announcement of the Longevity Dividend book, an extended argument for more government funding for the present mainstream approach to aging research, here is a position paper from one the researchers involved in this initiative:

The survival of large segments of human populations to advanced ages is a crowning achievement of improvements in public health and medicine. But, in the 21st century, our continued desire to extend life brings forth a unique dilemma. The risk of death from cardiovascular diseases and many forms of cancer have declined, but even if they continue to do so in the future, the resulting health benefits and enhanced longevities are likely to diminish. It is even possible that healthy life expectancy could decline in the future as major fatal diseases wane. The reason is that the longer we live, the greater is the influence of biological aging on the expression of fatal and disabling diseases. As long as the rates of aging of our bodies continues without amelioration, the progress we make on all major disease fronts must eventually face a point of diminishing returns.

Research in the scientific study of aging has already showed that the aging of our bodies is inherently modifiable, and that a therapeutic intervention that slows aging in people is a plausible target for science and public health. Given the speed with which population aging is progressing and chronic fatal and disabling conditions are challenging health care costs across the globe, the case is now being made in the scientific literature that delayed aging could be one of the most efficient and promising ways to combat disease, extend healthy life, compress morbidity, and reduce health care costs. A consortium of scientists and nonprofit organizations has devised a plan to initiate an accelerated program of scientific research to develop, test for safety and efficacy, and then disseminate a therapeutic intervention to delay aging if proven to be safe and effective; this is referred to as the Longevity Dividend Initiative Consortium (LDIC).

Link: http://dx.doi.org/10.1101/cshperspect.a025940

Comments

Hey there!

''...it is even possible that healthy life expectancy could decline in the future as major fatal diseases wane. The reason is that the longer we live, the greater is the influence of biological aging on the expression of fatal and disabling diseases. As long as the rates of aging of our bodies continues without amelioration, the progress we make on all major disease fronts must eventually face a point of diminishing returns.''

While true, in my opinion, therapies that are in the making are about to change that. They are very much health optimization through rejuvenation (albeit, it's not really Real biorejuvenation), more like 'Maintenance and Repair' (of current phenotype), rather than Reversal to Young Biological Stage Phenotype. Aging is a mixture of senescence and apoptosis. What creates these diseases (mostly) is inflammation (chronic and over long-term; acute too, but it's the chronic kind that is main culprit, for many diseases span a long time and were 'in the making' over a while (with or without apparent 'pain' symptoms (silent or not)). These diseases have a basis in inducibility, slow or quick (they can be triggered by genetic mutations, nucleotide bp errors) and they have a strong catalyst in inflammation. Inflammation promotes senescent cell formation (inducible senescence kind), the mostly oxidative stress (some rarer complications are due to 'Reduced Stress', when the redox is in a extremely 'reduced' state, the cells can die because ROS productions at complex I/III of ETC of mitochondria are completely quenched as the electrophile milieu becomes more and more reduced. When ROS are abrogated, the cell signals are abrogated too (ROS act as signals - while damaging) and that is just as bad). That is why the cell maintains a careful redox ratio balance of about 10:1,100:1 (GSG:GSSG), there needs to be a tiny amount of ROS in order for them to make the signals; this is evident in mito'hormemis' where mitochondria increase ROS production which triggers a survival signal : Nrf2 (Nuclear response factor-2) translocation in cell nucleus through ARE/EpRE, increase in membrane potential and activation of hundreds of Phase II ROS detoxicification enzymes; including the most important ones in the redox such as γ-Glutamyl-Cysteine Ligase and glutathione synthetase (which if, abrogated through siRNA/shRNA KO cancels all the effects of Nrf2); showing Redox is nearly responsable in entirety for hormesis effect)). In diseases, inflammation, acute or chronic, makes for senescent cell creation. This triggers an inducible senescence pathway that makes for the appearance of some of these diseases (most of them, since they are inflammation based; not all of them though as was stated before; but the major ones are strongly inflammation driven). It can be happen at any time in life, young or old; it is just that with age, there are less resources to work with, as such certain inflammation can take over; creating inducibility of senescence. Senescent cell clearance (such senolytics) will greatly reduce this inducible senescence and thus, these inflammation-triggered diseases (because senescent cell secrete inflammatory substances and cytokines such as TNF and INF-γ; which trigger a tumor/immune oncogenic activation of p53/p16/ras mediators of 'inducible' senescence). And so, it will compress morbidity period and allow people to live healther lives longer. What it will not do, though, is increase the 'theoretical' maximum lifespan of the human specie - that is the domain of replicative senescence (the intrinsic aging part which is constantly happening just like we breate air that contributes to this ROS formation and oxidative-telomere-dependent loss and late-activation of a special replicative senescence pathway); that is offset by stem cell renewal/differentiation (but that non-sexual stem cells themselves die too of this same pathway). But, for the future, we are definitely going to be able to live longer healthier lives as we remove the causes of this inducible senescence, which forms much of the inflammation for the diseases. The next thing will be how to crack the DNA replication problem when telomerase has been tried (Mrs.Parrish from BioViva who got 'telomerazed' herself as patient zero of her own company to show what will happen in terms of age reversal and cancer susceptibility formation) and could not stop things (because telomerase is shunted away from the nucleus (and it chromosomal telomeres) when oxidative damage happens, as such telomerase works only during 'low' ROS oxidative state to increase telomeres).

Hydrogen Peroxide Triggers Nuclear Export of Telomerase Reverse Transcriptase via Src Kinase Family-Dependent Phosphorylation of Tyrosine 707
1.http://mcb.asm.org/content/23/13/4598.long

Posted by: CANanonymity at January 11th, 2016 11:07 AM

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