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Changing the View of Aging: Are We Winning Yet? – Article by Reason

Changing the View of Aging: Are We Winning Yet? – Article by Reason

The New Renaissance Hat
Reason
June 28, 2015
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Peter Thiel, who has invested millions into the SENS rejuvenation research programs over the past decade, has of late been talking much more in public on the topic of treating aging. Having wealth gives you a soapbox, and it is good that he is now using it to help the cause of treating aging as a medical condition. One of Thiel’s recent public appearances was a discussion on death and religion in this context.

In the struggle to produce meaningful progress in rejuvenation research, the tipping point can come from either a very large amount of money, hundreds of millions of dollars at least, dedicated to something very similar to the SENS research programs, or from a widespread shift in the commonplace view of aging. At the large scale and over the long term, medical research priorities reflect the common wisdom, and it is my view that public support is needed to bring in very large contributions to research. The wealthiest philanthropists and largest institutional funding bodies follow the crowd as a rule; they only rarely lead it. They presently give to cancer and stem-cell research precisely because the average fellow in the street thinks that both of these are a good idea.

So it is very important that we reach a point at which research into treating degenerative aging is regarded as a sensible course of action, not something to be ridiculed and rejected. Over the past decade or two a great deal of work has gone into this goal on the part of a small community advocates and researchers. It is paying off; the culture of science and the media’s output on aging research is a far cry from what it was ten years ago. When ever more authorities and talking heads are soberly discussing the prospects of extended healthy life and research into the medical control of aging, it is to be hoped that the public will follow. Inevitably religion is drawn in as a topic in these discussions once you start moving beyond the scientific community:

Quote [Source: “Peter Thiel, N.T. Wright on Technology, Hope, And The End of Death” by Max Anderson – Forbes/Tech – June 24, 2015]:

The Venn diagram showing the overlap of people who are familiar with both Peter Thiel and N.T. Wright is probably quite small. And I think it is indicative of a broader gap between those doing technology and those doing theology. It is a surprise that a large concert hall in San Francisco would be packed with techies eager to hear a priest and an investor talk about death and Christian faith, even if that investor is Peter Thiel.

Thiel has spoken elsewhere about the source of his optimism about stopping and even reversing aging. The idea is to do what we are doing in every other area of life: apply powerful computers and big data to unlock insights to which, before this era, we’ve never had access. Almost everyone I talk with about these ideas has the same reaction. First there is skepticism  – that can’t really happen, right? Second, there is consideration  – well those Silicon Valley guys are weird, but if anyone has the brains and the money to do it, it’s probably them. Finally comes reflection, which often has two parts – 1. I would like to live longer. 2. But I still feel a little uneasy about the whole idea.

The concept of indefinite life extension feels uncomfortable to people, thinks Thiel, because we have become acculturated to the idea that death, like taxes, is inevitable. But, he says, “it’s not like one day you’ll wake up and be offered a pill that makes you immortal.” What will happen instead is a gradual and increasingly fast march of scientific discovery and progress. Scientists will discover a cure for Alzheimer’s and will say, “Do you want that?” Of course our answer will be “Yes!” They will find a cure for cancer and say, “Do you want that?” And again, of course, our answer will be “Yes!” What seems foreign and frightening in the abstract will likely seem obvious and wonderful in the specific. “It seems,” Thiel said, “that in every particular instance the only moral answer is to be in favor of it.”

One of Wright’s objections was to articulate a skepticism about whether the project of life extension really is all that good, either for the individual or for the world. “If [I] say, okay I’ll live to be 150. I’ll still be a sinner. I’ll still be conflicted. I’ll still have wrong emotions. Do I really want to go on having all that stuff that much longer? Will that be helpful to the world if I do?” This roused Thiel. “I really have to disagree with that last formulation…it strikes me as very Epicurean in a way.” For Peter Thiel, Epicureanism is akin to deep pessimism. It means basically giving up. One gets the sense he finds the philosophy not just disagreeable but offensive to his deepest entrepreneurial instincts and life experience. “We are setting our sights low,” he argued, “if we say everyone is condemned to a life of death and suffering.”

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Protein Modification as a Biomarker of Aging – Article by Reason

Protein Modification as a Biomarker of Aging – Article by Reason

The New Renaissance Hat
Reason
April 19, 2015
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The development of fairly consistent, accurate means to measure biological age – as opposed to chronological age – from a tissue sample is an important thread in aging research. Aging is a process of damage accumulation, and rejuvenation would be achieved through damage repair. Research and development aimed at significant extension of healthy life span can only become cost-effective given good ways to measure damage, however. There must be some reliable means to quickly assess the results of a treatment that claims a degree of rejuvenation through the partial repair of a specific form of cellular or molecular damage. In some cases this might seem easy. Take senescent cell clearance, for example: you run the therapy in mice, and compare a range of measures known to scale by senescent cell count in tissue samples before and after the treatment regimen. However, all that really tells you is how well the therapy clears senescent cells. All aspects of biology interact with one another, and age is a global phenomenon. To determine how aged an individual is and how effective a treatment might be when it comes to the practical outcome of additional healthy life span added there is presently little to be done other than wait and see.

The biggest challenge in the development of life-extending therapies is funding and cost. On the one hand there is far too little funding directed towards finding ways to treat aging. On the other hand effectively evaluating an alleged means of treating aging currently requires lifespan studies, and even in mice that takes far too long and costs far too much to be done casually. If there were standardized, quick and easy markers of physiological age that could be assessed before and after a treatment, then this research and development might be able to proceed ten times as rapidly, and evaluation of possible therapies would be open to far more research groups. There are many, many more laboratories with the capacity and funding to carry out a speculative $100,000 study versus a speculative $1,000,000 study.

All of this is to explain why there is considerable interest in developing a cheap biomarker of aging that can reliably assess physiological age from a tissue sample. No-one wants to run a five-year mouse study if there is a ten-minute alternative that produces an answer of about the same accuracy. That ten-minute alternative doesn’t yet exist, but some lines of research seem promising, such as work on DNA methylation patterns that appear to be fairly consistent among individuals over the course of aging. There is also the suggestion that the approach should be to measure the fundamental forms of damage thought to cause aging – but all of them, not just the one being treated by the therapy under consideration. At the present time that might be more onerous than finding a good set of secondary consequences that are reactions to damage, such as epigenetic changes.

The open-access paper linked below covers a fairly wide range of topics. The structures of our cells and tissues are built of proteins, and these proteins are constantly damaged and replaced. Many varied mechanisms toil constantly to remove proteins and cellular components as soon as they show damage or dysfunction. Nonetheless the difference between young tissue and old tissue is that old tissues have far more damage: misfolded proteins, malfunctioning structures inside cells, metabolic waste products such as advanced glycation endproducts (AGEs) gumming together structures in between cells, and so on and so forth. The damage leaks through, and even damage repair mechanisms are not invulnerable; they falter with age due to much the same set of issues as causes dysfunction elsewhere. In the future repair technologies, such as those outlined in the SENS proposals, will bring about rejuvenation by reversing these forms of damage. Since these issues are a part of full set of causes of aging, they are also potential markers of aging.

Protein modification and maintenance systems as biomarkers of ageing

Changes in the abundance and post-translational modification of proteins and accumulation of some modified proteins have been proposed to represent hallmarks of biological ageing. Non-enzymatic protein glycation is a common post-translational modification of proteins in vivo, resulting from reactions between glucose or its metabolites and amino groups on proteins, this process is termed “Maillard reaction” and leads to the formation of advanced glycation endproducts (AGEs). During normal ageing, there is accumulation of AGEs of long-lived proteins such as collagens and several cartilage proteins. AGEs, either directly or through interactions with their receptors, are involved in the pathophysiology of numerous age-related diseases, such as cardiovascular and renal diseases and neurodegeneration.
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Beside protein glycation, it is also well known that levels of oxidised proteins increase with age, due to increased protein damage induced by reactive oxygen species (ROS), decreased elimination of oxidized protein (i.e. repair and degradation), or a combination of both. Since the proteasome is in charge of both general protein turnover and removal of oxidized protein, its fate during ageing has received considerable attention, and evidence has been provided for impairment of the proteasome function with age in different cellular systems. Thus, these protein maintenance systems may also be viewed as potential biomarkers of ageing.
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It is expected that a combination of several biomarkers will provide a much better tool to measure biological age than any single biomarker in isolation. For the most part, the markers based on proteins and their modifications that have been chosen are directly related with mechanistic aspects of the ageing process. Indeed, they are relevant to such important physiological features such as protein homeostasis and glycoprotein secretion that have been previously documented as being altered with age. Therefore, it is expected that they may be less influenced by other factors not necessarily related with ageing.
Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Tomorrow Will Be Different From Today – Article by Reason

Tomorrow Will Be Different From Today – Article by Reason

The New Renaissance Hat
Reason
April 16, 2015
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We live in an era of very rapid change driven by technological progress. Today’s world is enormously different from that of three or four decades past: consider the pervasive effects of the revolution in communications and computing technologies that has taken place over that time. Yet, human nature being what it is, most of the people who lived through this profound shift in capabilities and culture are nonetheless very skeptical of claims that the future will look radically different from today in any important aspect. It is strange.

In particular the concept of actuarial escape velocity leading to thousand-year life spans is a very hard sell. People look at the large number that is very different from today’s maximum life span and immediately reject it out of hand, no matter the reasonable argument behind it. Any medical technology that produces some rejuvenation in old patients buys extra time to develop better means of rejuvenation. At some point the first pass at rejuvenation treatments will improve such that remaining healthy life expectancy grows at more than a year with each passing year. At that point life spans will become indefinite, limited only by accident or rare medical conditions not yet solved.

It doesn’t help that most of the public has very little knowledge of the present state of medical research in any field, never mind the specific details of how aging might be treated and brought under medical control. The only solution to that issue is to keep on talking: educate, advocate, and spread the word.

Quote:

It is likely the first person who will live to be 1,000 years old is already alive today. This is according to a growing regiment of researchers who believe a biological revolution enabling humans to experience everlasting youthfulness is just around the corner. At the epicentre of the research is Aubrey de Grey, co-founder or the California-based Strategies for Engineered Negligible Senescence (SENS) Research Foundation.

“The first thing I want to do is get rid of the use of this word immortality, because it’s enormously damaging, it is not just wrong, it is damaging. It means zero risk of death from any cause – whereas I just work on one particular cause of death, namely ageing.” de Grey said his research aims to undo the damage done by the wear and tear of life, as opposed to stopping the ageing process altogether. “If we ask the question: ‘Has the person been born who will be able to escape the ill health of old age indefinitely?’ Then I would say the chances of that are very high. Probably about 80 per cent.”

“The therapies that we are working on at the moment are not going to be perfect. These therapies are going to be good enough to take middle age people, say people aged 60, and rejuvenate them thoroughly enough so they won’t be biologically 60 again until they are chronologically 90. That means we have essentially bought 30 years of time to figure out how to re-rejuvenate them when they are chronologically 90 so they won’t be biologically 60 for a third time until they are 120 or 150. I believe that 30 years is going to be very easily enough time to do that.”

Link: http://www.news.com.au/technology/science/researchers-believe-a-biological-revolution-enabling-hu

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.