An interesting post over at In Search of Enlightenment:

Firstly, support for legitimate longevity science is hampered by the vast number of products currently being sold as "anti-aging" therapies without any science to substantiate their claims. See here, for example. And thus one has to be very careful when convincing people that (1) aging is something that ought to be retarded (as it increases our risks of morbidity and mortality); and yet at the same time convince them that (2) we might actually be able to slow human aging and yet (3) none of the current products being sold on the market have been demonstrated to do this (indeed, they might be harmful). The latter point is emphasized, for example, in this excellent piece in the Scientific American by Jay Olshansky, Leonard Hayflick and Bruce A. Carnes.

Now if one is pressing (as indeed I am) (1) and (2), it is of course understandable that people will be want to do something about aging (and thus be tempted to violate (3)). But when asked "So what can I do to slow aging?" my response is "(a) support increasing the amount of public funding we invest in the biology of aging and (b) encourage linkages between different fields of research-- from genetics and evolutionary biology to engineering and statistics". Well, as you can imagine, many people will find that answer rather flat! They want the solution and they want it now (today)! The same is true about climate change. Few people have an interest in being told the best solution is investing in new R&D and might be long-term. Patience never was a human virtue.

There's more in that vein, so take a look. I'm not in the "slow aging by massive government funding of the same community that's strongly resisted progress to date" clade, but the excerpt above is a fair summary of the immediacy problem - that once you've convinced people to think about healthy life extension on the merits, the natural result is a lot of waste and noise in addition to helpful additions to the community. That's the way that humans tend to act; we're given to look for the backsliding easy way out, even when we know it's not going to work. For every person who donates to the Methuselah Foundation's longevity research program, there will be another who decides to look into a new wrinkle cream.

You can lose a lot of sleep over things like this, but I think we advocates are better for accepting that other peoples' choices are not our responsibility. Everyone has free will; our task is to make better information available and persuade those who can be persuaded to help advance the state of longevity science. However well we do, there will continue to be a dubious "anti-aging" snake-oil industry and some number of people making poor choices.

If you're the type who likes to inspect the mechanisms behind the sausage, you should take a look at an article on Alcor's board over at Depressed Metabolism:

In January 2008, Alcor’s self perpetuating Board came under renewed scrutiny after long-time Alcor member and cryonics activist David Pizer tried to raise interest for changing the current system to a member elected Board.

Scrutiny of the board is a fine tradition for stakeholders in for-profit and non-profit initiatives, as is stakeholder activism to produce desired change. The concern voiced in the article is that born of the perceived need for change at Alcor - to better produce growth, increased professionalism, and so forth - and the concern that a self-perpetuating board has little incentive to make the changes that the writer would like to see happen.

Member-voted boards have their own issues, of course, not least that a member (as opposed to stakeholder) has no meaningful ownership right connected to their vote, but the pendulum swings as it chooses.

This is all, I think, I fairly good illustration of the transitionary period from volunteerism to professionalism one sees in any growing industry. The cryonics industry has been going through this phase for a long time, and remaining very small in size, for reasons that are much debated. Is it the fault of the business model, incredulous public perception, heavy regulation, a comparatively undiversified technology base, or the laundry list of other potential factors? Can be solved by changing the way people pay, by changes in regulatory structures, or by increased investment in research and building spin-off technology businesses? And so forth. These are all questions that have debated at length over the years.

What I think is most telling with regard to where the cryonics industry is at present is that you don't see a lot of discussion focused on change through competition. The traditional solution to undesirable characteristics within an industry is for entrepreneurs to set forth and compete, as "undesirable" usually means "customers will pay for something less undesirable." If you want change, then help to found a new company and do things the "right" way. Ongoing for-profit experiments in any number of different "right" ways are how progress is achieved and benefit brought to customers in the long term.

There needs to be more of that in the cryonics industry if the goal is directed change. The best way to make a board change their stripes is to look like you're going to eat their lunch out from under them; by doing that, you will also have gone a long way towards proving that your "right" way is in fact the right way for progress.

You might recall that the chemical alpha-synuclein is an aggregate that appears to be a proximate cause of Parkinson's disease (and like many biochemical aggregates, its buildup is slowed by the practice of calorie restriction). Researchers are delving deeper into the chain of mechanisms:

Patients with Parkinson's disease (PD) have elevated levels of the protein called alpha-synuclein in their brains. As the protein clumps, or aggregates, the resulting toxicity causes the death of neurons that produce the brain chemical dopamine. Consequently, nerves and muscles that control movement and coordination are destroyed.

The researchers discovered that the activity of three genes that control the synthesis of heme, the major component of hemoglobin that allows red blood cells to carry oxygen, precisely matched the activity of the alpha-synuclein gene, suggesting a common switch controlling both.

The scientists then found that a protein called GATA-1, which turns on the blood-related genes, was also a major switch for alpha-synuclein expression, and that it induced a significant increase in alpha-synuclein protein. Finally, they demonstrated that a related protein -- GATA-2 -- was expressed in PD-vulnerable brain cells and directly controlled alpha-synuclein production.

Researchers are taking a similar tack to that of mainstream Alzheimer's research now that a greater understanding of alpha-synuclein exists. Get rid of the aggregate, in other words:

"Simply lowering alpha-synuclein levels by 40 percent may be enough to treat some forms of Parkinson's disease," says Dr. Clemens Scherzer of Harvard. "So far, researchers have focused on ways to get rid of too much 'bad' alpha-synuclein in Parkinson patients' brains. Now we will be able to tackle the problem from the production site, and search for new therapies that lower alpha-synuclein production up front."

...

The studies showed that GATA-1 and GATA-2 proteins find the alpha-synuclein gene, stick to it and then directly control it.

"This is not an indirect pathway; it is direct regulation of the gene," says Bresnick. "This directness provides the simplest scenario for creating a therapeutic strategy."

The problem with influencing the production side is, of course, that everything in our biochemistry has many different roles. It's next to impossible to alter any gene or mechanism without causing unwanted side-effects. This is a strong incentive to focus primarily on cleaning up aggregates rather than re-engineering our metabolism, if those are the only two options on the table. Further options will hopefully emerge as researchers progress towards an understanding of why these mechanisms change with age. What form of known age-related biochemical damage is causing changes in GATA regulation - and thus alpha-synuclein levels - and how is it doing that?

How does one determine whether or not an advocacy website is actually working? A firm conviction that benefits are created is all well and good, but that won't get you very far in circles where resources are allocated on performance. The objectives of Fight Aging! are laid out in one of my annual signs of incredulity that I've been doing this for yet another year:

I have sought to bring those who stop by, or who otherwise stumble upon my writings, around to a more productive way of looking at aging, longevity, science and human action.

...

Sometimes our conversation is hard to find, however. People who might have learned and contributed do not do so; opportunities to broaden the healthy life extension community are lost. ... someone has to be talking on topic to keep the conversation growing, to avoid lapses in which newcomers might miss the party.

A nicely nebulous set of goals upon which to pin metrics. We can look at web statistics (one step beyond damned lies), participation in the healthy life extension community, funds raised for specific goals ... but it's a real challenge to determine what contribution my efforts made to a dynamic community or process of many contributers. Never mind how it could have all be accomplished more effectively or efficiently.

Those of you with longer memories will recall that sometimes people turn up out of the blue, lay down a seven-figure check, and say "yup, it was because of this advocacy initiative that I chose to donate." But it's rare - you can't base an analysis of success on huge checks from the blue. If you have enough of those to start counting, you've already won.

That particular seven-figure check justifies Fight Aging! for a good few more years yet, but vindication isn't really the purpose of metrics. Good advocates are one step removed from fanatics - they'll keep at it until the rest of the world gives in and admits the advocate was right all along. Metrics are about improvement: how can you do better with the resources to hand.

The online metric of first resort is web statistics, the damned lies mentioned above. I'm not all that sure that anything of worth can be derived from web statistics with respect to the goals of Fight Aging!. It's not even clear that more links, more traffic, or more aggregation are necessarily better - this is where those folk who are simply interested in monetizing websites have a much easier time of it. At the end of the day they can look at the dollars and rate of conversions to sale. Meanwhile I ponder the nature of my most popular page for this past year and wonder what most of my page views actually represent.

For Fight Aging!, a "conversion to sale" might be someone who sets off to become a molecular biologist or organize a fundraising conference for the Methuselah Foundation. I might be able to claim partial credit for one or two of those. At the less radical end of the scale, you'll find people who donate to fund SENS longevity research, or discuss healthy life extension with a friend where they might otherwise not have done. You get the idea - and I have no idea as to how well I'm doing there. Realistically, I'm never likely to know. Contributing to the new zeitgeist is not an activity for those who need personal validation, nor those who enjoy a nice, clean balance sheet of expenditure versus result.

So: I'm fairly convinced my work produces a continuing net positive influence, but proving that to anyone's satisfaction - beyond the genous million-dollar donor - is quite another story. In terms of improvement for the future, I'm left with the same old unsatisfactory metric of bulk visits and mailing list membership; I must assume that more is merrier until conclusively proven wrong on that front.

Jeriska continues the good work at Future Current, here posting a transcript of Gregory Stock's presentation at Aging 2008 last month:

Dealing with aging and death has always been a challenge. People have different ways of handling it. I see it in four categories: One is to just ignore it. This is pretty easy for awhile - you can just pretend it isn’t happening, particularly when you are young and when the manifestations of aging are not really apparent at all.

Another is, you deny it. "Death is not really real, because our soul will live eternally." Or, we will live eternally through our creations - those sorts of things. A lot of people like to feel that; it makes them feel better about the situation. Another is just to accept it. That is a common practice too, to say it is inevitable, natural, even the best thing. Leon Kass, for example, has said it is life’s finitude that gives it its meaning - as though young people who do not think about their mortality don’t enjoy life.

The final approach is to battle it. This was the strategy of Ponce de Leon, who was wandering around in the jungles of Florida. It could be Aubrey de Grey, too, who is trying to catalyze a serious effort to control the aging process. What is different now, though, is that suddenly, for the first time ever, it is actually quite plausible. As you heard from the comments of earlier speakers, we might actually be able to accomplish that.

What is interesting is that this is not the goal of biogerontology today. Its goal is not to control aging, or extend our natural lifespan, but to somehow compress morbidity, so that we can be healthier for a longer period of time and then fade away quickly. Initially that sounds reasonable, but at its logical conclusion, it really is completely out of sync with our aspirations.

As I've said elsewhere, the most important cultural battle of our time is that which started inside the gerontological community. It is the fight to build a research community whose members eagerly and vocally work to achieve what is possible with the future of biotechnology: the repair of aging and defeat of age-related degeneration.

At present that community is in only its earliest stages. The rest of the field is still mired in the views of yesterday, a place where no-one can talk about healthy life extension for fear of ridicule and loss of funding opportunities. Societies have a way of working themselves into a conservatism that holds back progress. This is slowly changing, but that change must continue and accelerate if we are to see significant progress within our lifetime.

A few points on cryonics and planning for emergencies from Aschwin de Wolf at Depressed Metabolism:

There are a lot of people who believe in the technical feasibility of cryonics and intend to make cryonics arrangements ... when necessary. As cryonics observers know, this is an extremely risky attitude because when people need cryonics the most, they often are unable to communicate their wishes, may meet resistance from relatives who benefit from their not making cryonics arrangements, or lack financial resources because life insurance is no longer an option to fund cryonics.

The best time to make cryonics arrangements is when it seems least likely that you need them soon.

Which is true of all preparation. As de Wolf also points out, cryonics - in the pleasant future in which for-profit cryopreservation concerns are established with solid business models and a sizeable presence - will remain an important critical care option even in the era in which science has conquered aging. Having rapid access to cryosuspension in the event of traumatic accident will be an important item of preparation for ageless individuals.

Many bridges remain to be crossed to reach that stage, not least in the expansion of the cryonics industry to a form in which greater growth and sustainability are ensured. For the moment, it's important to remember that thinking positively about cryonics isn't enough to ensure your cryosuspension. Some effort in preparation is required to ensure that you have the best possible chance of taking advantage of this alternative to the grave and oblivion.

The ability of immune system cells to identify and kill cells of a particular type of cancer varies enormously from person to person, even with medical interventions designed to point the immune system in the right direction. This is demonstrated in the variability of some forms of cancer vaccine:

When a tumor is surgically removed, proteins are collected, cultured and introduced in a Petri dish to dendritic cells taken from the patient's blood. The new, "educated" dendritic cells are then injected into the patient where they are intended to recognize and destroy lingering tumor cells. Patients receive three vaccinations at two-week intervals. A fourth vaccination is given six weeks after the third.

....

This study centered on the immune responses of 32 patients enrolled in a Phase II clinical trial. Seventeen patients had a significant positive response after three vaccinations; 15 showed no such responsiveness.

...

Forty-one percent of vaccine responders, compared to seven percent of non-responders, survived at least two years.

It is this variability that led to the work of Zheng Cui in transferring cancer fighting immune cells between mice, which you might recall from past SENS conferences:

the simple transfusion of the cancer-fighting immune cells from the resistant mice effectively transfered the same remarkable protection to the normal mice. And even more excitingly, the treatment didn't just prevent cancers from forming, but actually fought off existing cancer: when researchers transfused the anti-cancer white blood cells into normal mice with existing skin tumors, the tumors regressed completely in a matter of weeks. Moreover, a single dose of the cancer-fighting immune cells gave the normal animals a cancer immunity that often lasted for the rest of their lives.

A recent article looks at Cui's work and attitudes towards getting the job done - if you have something that demonstrably works, getting it to the clinic should run in parallel with figuring out how it works. That's a tough sell these days, however, yet another consequence of rabid over-regulation of medical research and development.

14 New Questions for Cancer Research Maverick Zheng Cui

First, we had cancer-resistant mice and asked, 'What can we learn from it?' The reason it’s resistant is because it has very different white cells. So then that immediately prompted the concept of therapy, because you can easily transfer white cells. You can extract them as a therapeutic agent and give them to another mouse. It’s a therapy. It’s much better than to find the gene. If you find the gene, then you have to understand the mechanism, and you have to find a way to put the gene into the cell, into all the cells you want to, and that would not work very easily. The technology as we speak right now is not really mature for that area. You might have to wait another 10, 20 years before that technology catches up with the concept. However, what we found is a cell as a therapeutic agent, so why not go ahead and see how it works. It worked really well in mice, so the next question, very obviously, is can we find a similar cancer resistance for humans as a donor for a therapeutic agent. And the answer is yes, we did find quite a few of them

...

A lot of people don’t like this because they said I have not a single idea of how it works. And I said, "Why should I?" If I can already go into therapy, why should I spend so much time now to find out how it works? That dispute was with the establishment, that’s why this trial has not been funded.

Via Marginal Revolution:

If [cryonics] works, the benefits are high, and the probability of it working is greater than zero. Yet few people sign up for it. I think that we are afraid of looking weird if we sign up for it.

The way to think about how and why people make decisions is to look at costs and benefits - which go far beyond mere money, of course. The discussion in the post revolves around "looking weird" as a cost. That's important for we folk descended from apes, possessed of a deep-seated and hardwired need for peer validation. Other costs exist, such as the need to get up and sort out paperwork - people die and become sick in many ways through similar laziness, especially in health matters stretched across the years. I think the comments to the post demonstrate that the more important costs are the perceived financial ones, however.

I suspect the eccentric childless millionaire demographic is overrepresented. Who else can afford it?

People look at the pay-at-the-door cost of cryonic suspension and decide they can't afford it, that cryonics is only for the rich. That is very much not the case, however. Next to no-one pays for their suspension in a lump sum at the door. Instead it's done via assignment of a life insurance policy for a very small number of dollars per month. There have been very few cryosuspensions of extremely wealthy people.

This suggests to me that if cryonics organizations want to grow, they should stop outsourcing organization of payment. Cryonics should be marketed from the very first touch to the potential customer as an insurance service you pay for monthly: people understand that, and do it all the time. What you are buying is cryosuspension should you be unfortunate enough to die, and the cryonics company handles the mechanisms of insurance - or however else the finances are sorted out - behind the scenes.

Monthly income for a company also allows for the sort of growth and professionalization that has been a challenge in the cryonics industry under the present model of funding for research and development. All in all, a potential win-win situation. One might ask why it hasn't been tried yet.

Biology is always more complex than first appears. I noticed a good example a few days ago, and have been mulling over what to say about it. You may have noticed that research into the biochemistry of progerias - accelerated aging conditions - has been picking up in recent years. The same is true of research into the mechanisms of calorie restriction, such as the importance of enhanced autophagy to health benefits conferred by the practice of calorie restriction. Progress has been made on both fronts, with the possibility of beneficial medical advances in longevity science resulting in the future. Much remains to be understood, however.

Here's a complication thrown into the picture built to date:

It is widely-assumed that the autophagic activity of living cells decreases with age and probably contributes to the accumulation of damaged macromolecules and organelles during aging. Over the last few years, the study of segmental progeroid syndromes in which certain aspects of aging are manifested precociously or in exacerbated form, has increased our knowledge of the molecular basis of aging. We have recently reported the unexpected finding that distinct progeroid murine models exhibit an extensive basal activation of autophagy instead of the characteristic decline in this process occurring during normal aging.

Further studies on Zmpste24-null progeroid mice, which are a reliable model of human Hutchinson-Gilford progeria, have revealed that the observed autophagic increase is associated with a series of metabolic alterations resembling those occurring under calorie restriction or in other situations reported to prolong lifespan.

So, what does this mean? That we've reached the point in the capabilities of biotechnology at which there is little more to be learned about "normal" aging from progerias? That progeroid mice eat less? That the stress effects of progeria upon cells trigger the same sort of response as the stress of calorie restriction?

Of such challenging questions is fundamental research made.

A number of folk from the longevity science and radical life extension advocacy communities were at last month's Idea City conference in Canada. A typically "balanced" but otherwise helpful article from the press showed up recently at the National Post:

The idea of youth restoration and life extension has long captivated the human imagination, from Dorian Gray's cursed portrait and Ponce de Leon's fountain of youth to cryogenic freezing and Botox.

Nowadays, the solutions range from the practical, such as Mr. Rae's extreme caloric tightrope, to the theoretical, which include scientific advances in tissue regeneration, biological tinkering to delay reproduction, and advancing the use of nanotechnology to repair the inner workings of the body with tiny cell-sized robots.

These kinds of futuristic solutions were a major focus of a recent conference in Toronto organized by Moses Znaimer, the 66-year-old media mogul who built his career on youth-driven television channels such as CityTV and MuchMusic and is now bent on rebranding 50-plus as the new watershed age for hip and active lifestyles.

"If you are having a good time and you are not in discomfort or disarray, we all want to live forever. Who wouldn't want to extend a happy and productive life?" he said.

But such a mission - life without end - is not without its detractors.

I can only imagine: "I'm writing an article on how good it is to breathe steadily and repeatedly - quick, find me someone to speak for the contrary viewpoint." Along those lines, here is an argument offered later in the article in favor of standing aside and letting billions of people suffer and die, who might otherwise have been saved:

"It's part of the natural cycle of things that life passes through these rhythms, one generation gives way to the next," he said. "We should be very careful about throwing that out.

"The world goes through change ... but we don't necessarily want to be the agents of some of that change."

Which is the same argument then marshalled by those who want to employ government force to make people suffer and die on a centrally-determined schedule - by blocking medical research and deployment of new technologies. Sometimes it's a challenge to live in peace with the asylum of would-be mass-murderers next door.