"We are on the verge of a revolution in medicine: understanding, treating, and ultimately preventing the causes of degenerative aging. But medical revolutions only happen if we all stand up in support of funding and research. We did it for cancer. We're doing it for Alzheimer's. We can do it for aging - and create an era of longer, healthier lives!"

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On the Causes of Aging
Accumulating AGEs
The Failing Immune System
Junk in the Lysosome
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Senescent Cells
Other Causes of Aging

Objections Answered
Boredom
Inequality and Economics
Overpopulation
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The Tithonus Error
What About Retirement?

Recent Entries

  • On the Psychology of Longevity Advocacy
  • Casting an Eye Upon Alcor's Board
  • The Murky Depths of Parkinson's Disease
  • How To Tell Whether It's Working
  • Gregory Stock at Aging 2008
  • Preparation is Only Helpful When Done Before You Need It
  • Cancer and Immune System Proficiency
  • The Economics of Signing Up for Cryonics
  • Always More Complex Than First Appears
  • Reporting from Last Month's Idea City Conference
  • The Membrane Pacemaker Hypothesis
  • Ask Aubrey de Grey About Longevity Research
  • The Mitochondrial DNA Deletions in Your Brain
  • Update on the Immortality Institute Folding@Home Prize
  • Unofficial Video From Aging 2008
  • Rejuvenation Research, Volume 11, Number 3
  • Revisiting Sirtuins Once More
  • The AnAge Database
  • Podcasts on Longevity Science and Economics
  • Friday Science: Aging, Stem Cells and Stem Cell Niches

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  • Thursday, July 24, 2008

    On the Psychology of Longevity Advocacy

    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.

    Wednesday, July 23, 2008

    Casting an Eye Upon Alcor's Board

    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 been 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.

    Tuesday, July 22, 2008

    The Murky Depths of Parkinson's Disease

    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?

    Monday, July 21, 2008

    How To Tell Whether It's Working

    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 generous 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.

    Friday, July 18, 2008

    Gregory Stock at Aging 2008

    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.