Future Current provides a valuable service by transcribing and making available the proceedings of meetings on transhumanist topics, such as healthy life extension and the ultimate defeat of degenerative aging. Two recent posts cover talks by Ronald Bailey and Anders Sandberg, given at the 2007 IEET event entitled Securing the Longevity Dividend. They are well worth your time as a reminder of the way in which the policy-focused world thinks.

Policy Scenarios for the Longevity Dividend

Here we have a very important driving factor, that is the belief that it is possible to extend life, which is not that widespread. People are in general very interested in life extension, but they don’t quite believe in it. I think this is very much the same situation as cloning before Dolly. I remember myself two weeks before the cloning of the sheep Dolly actually saying in a public forum, “Oh, cloning of mammals is years away.” It’s good to know that I’m a conservative guy that is sometimes wrong about the future. Life extension might come unexpectedly, and that’s not necessarily just a good thing, because some people might panic. On the other hand, if people don’t believe it’s possible, they won’t fund it.

It's only unexpected if we advocates haven't done our jobs - and the same goes for any alleged panic ("oh no, we don't have to suffer and die quite so soon..."). It seems to me that healthy life extension is a good deal more challenging than mammalian cloning, to the point at which it will take a very large and well supported research community to make real progress. It's more in line with cancer or regenerative medicine in that respect. No-one is going to be surprised by the advent of working rejuvenation therapies, for all the same reasons that no-one will be surprised by the development of cures for a broad range of cancers, or tissue engineered replacement organs.

The Political Economy of the Longevity Dividend

I would like to conclude that I think it is easily the case that these kinds of treatments are very likely to be affordable. The pro-mortalists fail to understand the effort to extend healthy human lifespan is a perfect flourishing of our uniquely human nature. The future generations will look back at the beginning of the 21st century with astonishment that some very well meaning and intelligent people actually wanted to stop biomedical research just to protect their cramped and limited vision of human nature. Those future generations will look back, I predict, and thank us for making their world of longer, healthier lives possible. To end, let me quote Sirtris Pharmaceuticals co-founder David Sinclair who said, "I would be disappointed if we were all born one generation too early." Me too.

For more information on the ongoing Longevity Dividend initiative that was the focus of this IEET event, you might look back in the Fight Aging! archives:

• Pitching Healthy Life Extension as the "Longevity Dividend"
• Criticizing the Longevity Dividend
• The Longevity Dividend: A Call for Endorsements

Random damage to your mitochondrial DNA is a bad, bad thing in the long term - or so present theory has it. It happens all the time in your cells, however, as a natural consequence of the mitochondria doing their intended job of turning food into ATP, the universal fuel source used by your cells. The standard issue process by which food becomes ATP is called oxidative phosphorylation (OXPHOS); it generates damaging free radicals as a side-effect of its operation. Those free radicals won't get far before running into some other molecule and reacting with it, changing or damaging it in the process.

OXPHOS requires several key portions of your mitochondrial DNA to be intact and undamaged - or rather it requires the proteins that are created from those DNA blueprints. Now, if the needed portion of mitochondrial DNA is altered or destroyed by free radicals churned out by the OXPHOS process - well, no more OXPHOS for that mitochondrion. No more free radicals, either, and that's a more serious problem:

• Sufficient free radical damage to mitochondrial DNA shuts down OXPHOS within that mitochondrion, as the necessary proteins can no longer be produced. The mitochondrion switches over to using a less efficient method of producing power, one that doesn't produce free radicals, but has to run at a much higher rate to produce the same level of ATP.

• Mitochondria, like most cellular components, are recycled on a regular basis. Components called lysosomes are directed around the cell in response to various signals, engulfing and breaking down damaged or worn components. After the herd has been culled, surviving mitochondria within a cell divide and replicate, much like bacteria, to make up the numbers - this is called clonal expansion.

• The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it's old, leaky, inefficient and needs to be replaced with a shiny new power plant.

• BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS, it will no longer be producing free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either.

• One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started.

These cells entirely populated with damaged mitochondria start churning out large quantities of free radicals - through another, more forceful mechanism - into the body at large. That's a path to age-related degeneration and fatal conditions like atherosclerosis. The free radical theory of aging is based upon the harm done to tissues, structures and processes by these damaging biochemicals.

So how does this all get started again? Free radical damage to mitochondrial DNA? Possibly. There has been some debate of late as to how plausible this is as a mechanism, based on mutation rates, examinations of mitochondrial function in mice with many damage-induced point mutations in mitochondrial DNA, and so forth. With that in mind, I noted with interest a recent Nature Genetics paper:

What causes mitochondrial DNA deletions in human cells?

Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central role in the aging of postmitotic tissues. Understanding the mechanism of the formation and subsequent clonal expansion of these mtDNA deletions is an essential first step in trying to prevent their occurrence. We review the previous literature and recent results from our own laboratories, and conclude that mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process.

Deletion mutations are much more damaging than point mutations, and can result in a sequence of many genes being snipped out and lost. Thus a greater likelihood of losing one of the genes vital to OXPHOS. This paper presents an interesting nuance to the source of deletions - serious damage created as a result of errors in the processes that repair minor damage due to OXPHOS free radicals. Irony abounds throughout the mitochondrial free radical theory of aging.

To switch gears a little, I should note that the beauty of the Strategies for Engineered Negligible Senescence (SENS) approach to the mitochondrial free radical theory of aging is that it doesn't require medical engineers to understand why the damage happens. If we can successfully move genes that express the proteins vital to OXPHOS into the cellular nucleus, it then doesn't matter what happens to the mitochondrial DNA, OXPHOS will keep on working.

Similarly for wholesale replacement strategies - we don't need to know how the damage occurred to know that protofecting fresh, undamaged mitochondrial DNA into every cell will fix things for a while. "A while" being at least 30 years, given how long it takes the problem to become damaging to health.

Research is good - there is no such thing as useless knowledge, and every additional level of detail helps those building new therapies. But never feel as though there isn't enough to go on with already when it comes to engineering the repair of aging. Researchers know more than enough to be underway, and it's a tragedy that the field of aging repair - real rejuvenation medicine - is far less funded than present understanding merits.

A good scientist is one who takes the time to write introductory papers for researchers outside his speciality, in related research communities that would would benefit from the latest findings, but are unlikely to make their own way to the water. As knowledge grows and science becomes increasingly specialized, each researcher's field of vision a smaller and smaller fraction of the whole, the process of spreading, assimilating and managing information becomes just as important as generating new knowledge.

We lay people also benefit from clear papers that outline the present state of knowledge. Here, for example, is a concise outline of we know about the practice of calorie restriction and its relevance to health and longevity:

An epidemic of overweight/obesity and type 2 diabetes, caused by overeating nutrient-poor energy-dense foods and a sedentary lifestyle, is spreading rapidly throughout the world. Abdominal obesity represents a serious threat to health because it increases the risk of developing many chronic diseases, including cardiovascular disease and cancer.

Calorie restriction (CR) with adequate nutrition improves cardiometabolic health, prevents tumorigenesis and increases life span in experimental animals. The purpose of this review is to evaluate the metabolic and clinical implications of CR with adequate nutrition in humans, within the context of data obtained in animal models.

It is unlikely that information regarding the effect of CR on maximal life span in humans will become available in the foreseeable future. In young and middle-aged healthy individuals, however, CR causes many of the same cardiometabolic adaptations that occur in long-lived CR rodents, including decreased metabolic, hormonal and inflammatory risk factors for diabetes, hypertension, cardiovascular disease and cancer.

Unraveling the mechanisms that link calorie intake and body composition with metabolism and aging will be a major step in understanding the age-dependency of a wide range of human diseases and will also contribute to improve the general quality of life at old ages.

The evidence to date suggests that, barring medical conditions that prevent it, we should all be giving calorie restriction a good long try. The future is pretty scary place if you believe it to involve the full range of obesity-linked degenerative conditions: Alzheimer's, diabetes, heart disease, cancer. Why gamble on the advance of medical technology to rescue you in time from the consequence of bad diet and little exercise? As I've noted in the past, there is already a great deal you can do today, and in the years ahead, to raise your chances of living healthily into the age of working rejuvenation medicine.

Think about it; if you can stash money away in your retirement fund for a time decades distant, why don't you apply the same level of thought and resources to investing in your future health?

Aging is a medical condition - a disease, if you will. Like many medical conditions it is the result of damage and changes in your biochemistry that accumulate over the years. As for all medical conditions, we can look for therapies that postpone or reverse its effects. We can - and should - search for a cure.

In that vein, the Methuselah Foundation is playing host to a conference on the scientific path to rejuvenation medicine in Los Angeles this coming June.

The preliminary program already has over two dozen confirmed speakers, all of them world leaders in their field. As for previous conferences I have [co-]organised, the emphasis of this meeting is on "applied biogerontology" - the design and implementation of biomedical interventions that may, jointly, constitute a comprehensive panel of rejuvenation therapies, sufficient to restore middle-aged or older laboratory animals (and, in due course, humans) to a youthful degree of physiological robustness.

Those of you who follow the latest aging research will recognize many of the names already in the program, and note that the Methuselah Foundation continues to draw together work from different fields in the Strategies for Engineered Negligible Senescence (SENS) approach to the repair of aging.

The conference is preceded by a more press-friendly symposium at which noted folk from the healthy life extension advocates and members of the aging research communities will speak:

The free public preconference "Aging: the disease, the cure, the implications" [will] be held in the 1800-seater Royce Hall, UCLA, on the evening of Friday June 27th, and to the dinner and reception following. This preconference will put the postponement of aging more firmly on the political and social map than ever before.

It will consist of presentations by at least six illustrious speakers, including:

• William Haseltine, Haseltine Global Health, founder of Human Genome Sciences
• Bruce Ames, Children's Hospital Oakland Research Institute, National Medal of Science awardee
• Michael West, Biotime Inc., founder of Geron and Advanced Cell Technology
• Daniel Perry, Director of the Alliance for Aging Research
• Gregory Stock, UCLA Program on Medicine, technology and Society and Signum Biosciences

Mark your calendars - this is something of a "SENS California," and promises to be much like the SENS conference series organized by biomedical gerontologist Aubrey de Grey in recent years.

Given the members of the advisory committee for the Grand Challenges for Engineering, there appears to be a large and obvious hole in the list of challenges offered for consideration. Researcher Attila Chordash asks the obvious question:

Why was life extension ruled out of the 14 Grand Engineering Challenges?

...

It is a big challenge to learn how could healthy lifespan extension as a big and realistic challenge have been left out? Why did Kurzweil (author of the book Fantastic Voyage: Live Long Enough to Live Forever) not stand up for it? Why nobody out of the luminaries thought that regenerative medicine and stem cells worth discussing more than a tiny side note? And what about Venter, whom I still like to be interview as there are many points in his activity suggesting a life extension connection. Somebody in the committee was clearly against it?

I was also surprised, given the tenor of press articles on the Grand Challenges, most of which focused on Ray Kurzweil and his views on the future of radical life extension and other transhumanist technologies. Given a committee, it seems, you can water down any set of ambitions to thin gruel indeed.

American inventor and futurologist Ray Kurzweil said mankind is on the brink of radical advances in computer science and medicine that will see tiny robots or "nanobots" embedded in people's bodies, fending off disease and boosting our intelligence. Breakthroughs in technologies such as RNA interference, involving inhibiting the functioning of genes, and gene therapy will allow us to flick genetic switches on and off and add new ones - putting an end to many illnesses and expanding lifespans, he added.

Precious little of that in the Grand Challenges themselves. Chordash offers some opinions collected from his network; it boils down to the conservatism of the any old guard, scientific community or otherwise. But there is no debate on the feasibility of healthy life extension in the gerontological community these days; the arguments are all over how the goal will be accomplished, how much can be done, and how long it will take. When you put together a Grand Challenge for Engineering on medicine and manage to completely leave out extending the healthy human life span, you make yourself irrelevant to what is actually taking place in the laboratories and research communities today.