As Chris Patil notes, things have moved fast in the field of sirtuin research:

The work represents the culmination of a huge amount of progress in a relatively short time: in less than 15 years, the sirtuin story has evolved from basic biology in the simplest model organisms, through exhaustive (though essential) testing in larger animals, into a source of potential therapies for a major human disease.

Furthermore, for the first time we have a clearly defined path toward the regulatory approval and widespread use of a compound that could be used as a frank anti-aging drug.

It's a good model for modern biotechnology research - an example of the speed with which mechanisms can be traced and understood, once a starting point is made. The process is ongoing, for many other proteins and genes related to beneficial metabolic response to calorie restriction. Sirtuins are just the start.

I would not, however, agree that it is a good model for the application of such research. One can applaud the success of researchers in obtaining funding and carving out a viable, competitive, well-funded field from the first studies of genes and calorie restriction. But the path to applied longevity science is not to call triumph at finally pushing something (anything!) past the impossible hoops blocking applied aging research - it should be to destroy the regulatory nonsense rules preventing progress.

Why, despite the great range of potential applicable biotechnology, do we not see hundreds of millions of dollars invested in startups attempting to address the aging process? The answer is buried in this New York Times article on Sirtris: "Dr. Westphal and Mr. Sinclair stress that they are not working to 'cure' aging, a condition that, so far at least, is common to all humanity and that most physicians do not consider a disease. 'Curing aging is not an endpoint the federal drug agency would recognize,' Dr. Westphal says dryly. Instead, both men say, they are working to ameliorate the diseases of aging." For so long as unelected government employees can declare, with no accountability and full force of law, what medicine is permitted and what is not, there will be no direct venture funded efforts to cure aging - or even to take the first steps by aiming to repair specific, identified age-related damage in order to intervene in the aging process. There is no lack of companies, research groups and billions of dollars ready to be directed to that end, as any brief survey of the biotechnology marketplace will show you - but the ignorant few who write policy continue to bury all that potential. The work that could have gone to advance the cause of healthy longevity is instead confined towards the backwaters of patching specific age-related conditions.

The press is running another round of articles on Sirtris Pharmaceuticals at the present time, focusing on the next line of drugs that improve greatly upon the basic model of resveratrol - at least in terms of their effectiveness in stimulating sirtuin activity.

The potent new pills mimic resveratrol in mice by activating the SIRT-1 gene, which appears to trigger a process called caloric restriction. In many organisms, that process acts to slow down aging and ramp up cellular defenses in the face of a reduced diet during times of scarce food supplies. Sirtris's new compounds, however, act without the little critters having to reduce their diet.

As most of you probably know, I'm not convinced that this is all any more than a sideshow. For one, it is in no way an attempt to directly repair the damage of aging, and for two, for so long as the present regulatory structure forbids the development and commercialization of real, working anti-aging medicine, there is no financial incentive to develop real, working anti-aging medicine. Even if you have a promising start, of any sort, every venture-funded, competitive effort to turn science into medical technology will go towards turning that start into a patch, an after-the-fact and comparatively ineffective treatment for some age-related condition, rather than a treatment for aging itself.

Here is a simple rule for life: you won't accomplish task A by working on task B. That task A is cut off by regulatory fiat is the real problem here.

Researcher S. Jay Olshansky will be the guest at the next Sunday chat hosted by the Immortality Institute:

I am happy to announce SJ Olshansky will be joining Imminst for the Sunday Night Chat this Sunday December 2nd at 6:30pm CST U.S. If you are not familiar with Professor Olshanksy...you should be. He was researching methods to slow aging while most Imminst members were still in diapers. He has seen all the hype, the successes, and failures. His latest endeavor is the The Longevity Dividend, which proposes to set aside 3 billion (that's billion with a B) dollars a year of NIH funding for the study of aging.

Chat Room: http://www.imminst.org/chat

Sun December 2nd
- 4:30 Pacific
- 5:30 Mountain
- 6:30 Central
- 7:30 Eastern

You can look back in the archives here for much more on the Longevity Dividend:

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

As far as I can see, Olshansky is in the camp of "metabolic re-engineering and slow but solid progress in slowing aging is the way ahead, but it'd be wonderful if things that worked far better were demonstrated to be plausible." Which is hopefully a transitionary stage on the way to "I always thought that the Strategies for Engineered Negligible Senescence was a great idea." We'll see.

One of the constants of our present age of change and progress is that biology is always more complex than first thought. It's a given. Evolution is under no constraint to produce designs that fall within the bounds of complexity we feel comfortable taking in at one sitting.

The scientific community will still master our biology - reverse-engineer it, replicate it, and ultimately greatly improve on it - but we shouldn't be surprised when hoped-for simplicities in biological mechanisms fail to materialize. That's all the more reason for greater support and funding for efficient, goal-driven medical research.

MIT: Stem-cell therapies for brain more complicated than thought:

MIT scientists report that adult stem cells produced in the brain are pre-programmed to make only certain kinds of connections - making it impossible for a neural stem cell originating in the brain to be transplanted to the spinal cord, for instance, to take over functions for damaged cells.

...

"A stem cell that produces neurons that could be useful to replace neurons in the cerebral cortex (the type of neurons lost in Alzheimer's disease) will be most likely useless to replace neurons lost in the spinal cord. [Moreover], because there are many different types of neurons in the cerebral cortex, it is likely that we will have to figure out how to program stem cells to become many different types of neurons, each of them with a different set of pre-specified connections."

"In the stem cell field, it is generally thought that the main limitation to achieve brain repair is simply for the new neurons to reach a given brain region and to ensure their survival. Once there, it has been assumed that stem cells will ‘know what to do’ and will become the type of neuron that is missing. It seems that is not the case at all. Our experiments indicate that things are much more complicated."

The Immortality Institute volunteers are upgrading; always a painful process with a large forum and a content management system extensively customized over the years. If you haven't stopped by the Institute forum in a while, you should do so. Where else are likely to be able to participate in a discussion on the first recorded practitioner of calorie restriction - and noted author of the Renaissance - with researcher S. Jay Olshansky and other noteworthies?

A noble idea is a noble idea, and we shouldn't be surprised to find people from the past with constructive contributions to make on the topic of healthy longevity - taking into account the state of scientific knowledge in their time:

Sixteenth century Venetian Ambassador and Renaissance Christian Luigi Cornaro was celebrated in his time for his stance on dietary self-restraint, moderate living, and living to the age of 103. For these hundred of years his classic book has survived as a renowned text on longevity and an inspiring treatise on the path of temperance that the author believed could lead anyone out of a state of illness and into a healthy long life. The Art of Living Long contains Cornaros four discourses, respectively concerned with demonstrating his ideas through his own example, exploring the necessity of temperate habits, assuring a happy old age, and exhorting mankind to follow his rule. With introductions by Dr. Gerald Gruman and Joseph Addison, and additional essays by Lord Bacon and Sir William Temple.

To take a contrary point of view, however, is this really any different - important names of centuries past aside - from the standard mainstream media coverage of centenarians today? The form requires the journalist to ask for the centernarian's thoughts on longevity, but living for a long time doesn't make you an expert on how to live for a long time. Everyone has an opinion on how it is they've lived so long, but opinion isn't science.

When you're wandering through the vast libraries of writing on the topics of aging and longevity, remember that the scientific method is how progress is made. Opinions can be good, can be well-thought, can even be right as it later turns out, but opinions alone are not the foundation for a path forward.

This caught my eye while I was meandering my way through PubMed; a nice turn of phrase in this way of looking at the mechanisms of aging and the future of aging in a world shaped by human action.

Senescence Viewed through the Lens of Comparative Biology:

Although mortality and longevity are inherently biological phenomena, their study has historically been the purview of demography and the actuarial sciences. An infusion of biological thinking into these disciplines transforms demography into biodemography and provides expectations and coherency to observations on age-determined mortality that would not be explainable otherwise.

Comparative biology teaches us that reproduction is life's solution to the inevitability of death in the hostile environments of Earth. That solution, however, places a higher priority on investing physiological resources into reproduction that could otherwise have been used to maintain the soma (body) longer. As such, aging is an inescapable but inadvertent byproduct of imperfect maintenance and its attendant surveillance and repair. Biology also reveals that while bodies are not designed to fail, neither are they designed for extended operation. In other words, bodies are subject to biological warranty periods for normal operation. For sexually reproducing species, that warranty period includes the time from conception to sexual maturity, the production and nurturing of offspring, and a period of grand-parenting in some species.

Humans are the only species capable of exploiting the loophole in the biological contract of life (bodies that are not designed to fail). Human ingenuity (science, medicine, public health) has produced interventions that manufacture survival time by delaying death, and in so doing, has created a phenomenon never before seen in the history of life - population aging (and all the societal and health consequences that go with it).

Aging and individual death might well be the inevitable consequence of evolutionary pressure on cellular life, but it's far more noteworthy that we have the capacity to do something about it. Intelligence and technology are a loophole big enough to created physical immortality - given enough resources and time. The big question is whether the first stages on the road to the repair of aging and greatly increased healthy life spans happen rapidly enough to benefit you and I, or whether cryosuspension will be our only opportunity.

The choice is ours; how much do we want healthy longevity and how much are we prepared to work towards that goal?