Sí se puede

Just to follow up on that last post asking you to help the SENS Foundation win $5000 — it worked! SENS came in first, and won the grand prize. The margins were pretty narrow — well below the number of people who visited the contest page from Ouroboros alone — so it can truly be said that every vote counted.

Thanks to the readers of Ouroboros and everyone else who helped SENS over the top.

The amount of money raised is, in the grand scheme, rather small, but it’s possible that the victory for SENS in what amounts to a popularity contest will help increase awareness of the life extension cause.

“I’m immensely grateful to 3banana for involving us in this great opportunity, and to all the SENSF supporters who took the time to leave comments at the site,” said SENS Foundation CSO, Dr Aubrey de Grey. “These supporters have recognised that a public and eloquent expression of broad-based support for our mission has the potential to raise the profile and perceived legitimacy of our work and thereby greatly amplify the impact of the competition itself.”

 

The wonderful hyperbole of Oz: Popular media overstate the benefits of CR

Over at Fight Aging!, Reason spanks Oprah and sensationalist popular-medicine author Dr. Oz for promulgating unrealistic expectations about the lifespan extension benefits of CR:

Hence for a discussion of longevity, wild and unsupported claims are fair game. At the present time, the scientific consensus is that human practice of calorie restriction will not greatly enhance maximum longevity, but does greatly improve health and greatly reduce risk of age-related disease. That isn’t as exciting, however, as earlier speculation on attaining 120 year or more life spans, so the more exciting “fact” is what gets aired:

Dr. Oz says calorie restriction is the number one way doctors say we can extend longevity. “The data that we have in rodents and some larger animals now indicate you can probably extend your life expectancy by up to 50 percent potentially from doing this,” he says.

Don’t get us wrong: As Reason takes care to point out, CR is almost certainly good for you. Biogerontologists have shown that CR yields benefits at the molecular, mitochondrial, and cellular level, and it’s likely to improve human health. It is not clear, however, whether CR will extend the human lifespan to the extent seen in short-lived animal models; indeed, there are reasons to believe that it won’t.

(Qualification: the definitive studies are ongoing and haven’t been completed yet — by their very nature, they take a long time. The issue is still controversial, in the way that issues often are when the data’s not in yet. The scientific consensus hasn’t really been established; to the extent that there is one, it’s based on extrapolation from preliminary data, and the jury is still out.)

On the show appeared members of the Calorie Restriction Society, who are plugging the broadcast on their website. (I want to preface the following by saying that I generally respect CRS; I’m pretty picky about what goes into the blogroll). In light of Reason’s commentary, I realize that their website is rhetorically slanted in favor of the claim that CR confers life extension: from their motto (“Fewer calories. More life.”), to the big graph of rodent lifespan curves on the front page, to the conclusion that CR is a “proven life-extension method” (eliding the lack of definitive human data), the site is rich with implication that CR will extend longevity — a claim that hasn’t been proven.

CRS could be doing a lot better job of portraying the subject in a scientifically accurate way — toning down the implications about certain lifespan extension, focusing on the more clearly established health benefits, and giving voice to countervailing studies. Openness about the weaknesses of a theory, after all, are part of the rigorous logical testing that produces better theories. And just as with book reviews, acknowledging the negative might go a long way toward increasing the credibility of positive claims about CR.

 

“When Cells Grow Old”

There’s a good non-technical overview of cellular senescence, with interviews from some of the field’s luminaries, in the most recent HHMI Bulletin:

Adding just four genes can turn adult cells back into embryonic-like cells, able to develop into any cell type in the body, according to Daley’s studies. In culture dishes, cells from a younger postdoctoral fellow in Daley’s group were “youthful and vigorous,” he says; many of them morphed into stem cells. But Daley’s cells were stubborn, refusing to reverse their clocks. It seems as a person ages, cells get increasingly stuck in their ways.

Daley isn’t taking it too personally. “I’m deficient in a lot of things, and reprogramming seems to be one of them,” he says. He plans to use the observation to understand how to reprogram cells most efficiently.

His finding points out an important concept: cells might not sprout gray hair, get achy joints, or forget where they put their car keys, but they do age. Several HHMI researchers are just beginning to learn what happens to cells as they grow old, and they’re making connections between those changes and cancer, deficiencies in wound healing, and other problems that increase in likelihood as a person ages.

It’s a great piece for a reader who might be interested in cellular aging but not have the technical background required to tackle the primary literature. I’m definitely going to put it in the list of pages I send friends when they ask what I work on.

In other news, the HHMI Bulletin is actually pretty good. In the past I’ve turned up my nose at “pet” magazines published by institutions, but recently I’ve given several of them a chance and been pleasantly surprised.

 

Signtific: “The future of science and technology”

The Institute for the Future has recently launched a future-forecasting forum called Signtific. The basic idea is that users will post short entries about significant upcoming changes (“signals”), combine their own signals with those of others to identify major shifts or disruptions that may arise in the future (“forecasts”), and discuss the ideas that emerge. It’s somewhere between a social networking site and a brainstorming session.

Activity is pretty low at the moment, though the site is still fairly new — so far no one has even initiated a conversation about biogerontology or related technologies, which clearly fall under the umbrella of significant future changes (hence my suspicion that Ouroboros readers would find this interesting) — but hopefully more people will join in as time goes on.

 

Prometheus, snugly bound: The institutional barriers against scientific risk-taking

A nice piece about the systemic challenges facing academic biologists appeared in Olivia Judson’s blog, The Wild Side. The post, entitled Letting Scientists Off the Leash, was written by Stephen Quake, an HHMI investigator currently working at Stanford University. Rather than excerpt the item itself, I’ll reproduce the commentary of our friend and former contributor Lev Osherovich, at his blog William Butler Yeast:

Steve Quake has a totally spot-on op-ed piece in the NY Times Science blog about the medieval economics of academic science. In brief, competition for scarce funding together with the role of university bureaucracies as intellectual slumlords traps researchers in an endless grant-writing cycle that demands conformity and quashes creativity. One of the commentators correctly points out that this state of affairs is a consequence of massive overproduction of Ph.D. scientists.

I’m not in complete agreement with everything Quake says. In particular, I think he massively understates the extent to which private foundations are subject to the same conservatism as government agencies. Granted, the Howard Hughes Medical Institute does allow its investigators a lot of freedom, but one can only get an HHMI grant after succeeding for a decade or more at the plodding drudgery of NIH grant-writing. This generates a sort of Peter Principle effect: a professor is rewarded for long-term success at inside-the-box thinking by finally being let outside of the box and told that they can do whatever they want. Sadly, a dog that has been chained in the same spot for a long time will tend to stay in that spot long after they’re let “off the leash.”

Also, he has a weird understanding of what a “market” is, which makes for some strange reading in the middle of the piece.

I’m willing to give him a lot of latitude, however, since he’s so compelling on his main theme of institutional barriers to creativity in extramurally funded research. He even suggests a fairly straightfoward solution: rather than forcing scientists to support their own wages and their lab funding from the same grant-derived pot, simply guarantee their salary and let them apply for grants for resources beyond that minimum amount. That way, scientists won’t be gambling their ability to pay the mortgage on each grant proposal, and they’ll be more likely to take genuine risks.

(It’s worth mentioning that Quake is a recipient of the prestigious HHMI investigator award. If he thinks the situation is bad, then it’s bad.)

 

Methuselah gets rejuvenated

The Methuselah Foundation website has undergone a redesign; the new site is pretty slick. Stop by and check it out.

The old URL for the Methuselah Mouse Prize, mprize.org, now redirects to the main Foundation website. The new Prize page is now here.

For those of you who can’t get enough updates from aging-related blogs, they’ve moved the RSS feed republications off the front to this page.

 

Hourglass VI: A carnival of biogerontology

For its sixth edition, Hourglass returns home to Ouroboros. I think the holidays have resulted in a bit of contraction of effort all around the blogosphere, so this installment is a little…”cozy”. Still, I think we have quite a range of excellent articles featured in this issue:

The Predicated Life is a blog by Matt Farrell, who is engaging in alternate day fasting (ADF) in part for general health reasons and in part to help alleviate joint inflammation. (This idea is theoretically well-motivated if not yet widely tested: ADF increases levels of the longevity assurance factor SIRT1, and SIRT1 activity decreases inflammation.) Matt shares two pieces about his experience: On Knees and Inflammation, which isn’t especially about either topic but rather about strategies for controlling appetite when one is engaging in ADF; and The Nuts and Bolts of How Alternate Day Fasting Actually Works, where Matt delves into the evolutionary explanation of why one might expect ADF to be a good idea.

Mmmm…nuts and bolts.

Reason at Fight Aging! submitted posts describing two different aging-related organizations.

One is the Millard Foundation, a California-based non-profit whose “primary purpose is to promote bringing true regenerative medicine and greater, healthy longevity to humanity.” MF is just starting to stretch its wings in the funding arena, and is focusing its largesse on strategies devoted to repair (rather than delay) of age-related damage.

The second post regards a commercial enterprise, Sierra Sciences, currently working to develop telomerase-related therapeutics; Reason takes the opportunity to talk about the ways in which telomere-centric theories of aging have evolved over the course of the past decades, and emphasizes that the jury is still out on the ultimate role that telomerase will play in regenerative medicine.

While the role of telomerase in aging-related therapeutics remains undecided, biogerontologists remain convinced of the merits of studying telomere biology. Fueling the fire are studies like the recent report (blogged here) that telomerase expression slows aging — at least in a mouse that’s already tricked out to be highly cancer resistant. While it’s unlikely that we’ll be engineering cancer-resistant humans anytime soon, results like this suggest that ways to conditionally activate telomerase (and then shut it off again) might have profound effects on tissue regeneration.

Wrapping up the carnival, Ward Plunet at brainhealthhacks shares a length, thoughtful and wide-ranging post entitled Longevity: Think of yourself now, and yourself in the future. Ward discusses the future of the longevity field, and then describes at length a study that has evaluated the human capacity — or lack thereof — to think rationally about the future.

That’s all for now. If you’d like to host a future installation of Hourglass, please email me.

 

2008 Hillblom meeting: Morning session 1B

(continued from our coverage of the earlier session)

I’m going to cover just one talk from this session, from Charlie Glabe, who gave two of the more exciting talks at the last two LLHF meetings (see my review of the 2006 and 2007 meetings).

Glabe’s group (including several other PIs joined by a LLHF network grant) has been developing anti-amyloid antibodies, some of which are conformation-specific but not necessarily sequence-specific; in other words, antibodies that recognize common features of amyloid aggregates formed by many different types of protein (e.g., Aß but also alpha-synuclein, IAPP, and other peptides involved in aggregation-based diseases). These reagents will be useful in research but also potentially as therapies against multiple age-related illnesses.

Since last year, the group has been attempting to determine the structure of amyloid oligomers. Problem: amyloids don’t crystallize, so the current strategy is to form co-crystals between anti-amyloid antibodies and prefibrillar oligomers — or, failing that, crystallize the antibody alone and make inferences about the amyloid structure (which should be the ‘negative space’ of the antibody Fab fragment — assuming, of course, that the antibody doesn’t have to undergo a dramatic structural rearrangement in order to bind). Another member of the collaboration has been trying to understand the folded and unfolded states of amyloidogenic proteins, using solution-based techniques (EPR, NMR) rather than crystallography.

Another new direction in this project: studying the effect of amyloid oligomers on membrane conductance. Amyloid oligomers, which are toxic to cells, have a significant effect on the electrical properties of lipid bilayers: specifically, they increase the rate of depolarization. Novel, and this will be especially relevant to the emerging idea that AD is a disease of neuronal connectivity (i.e., interfering with membrane conductance) as well as cell toxicity.

Not a whole lot of new stuff on the therapeutic angle this time around, but you can’t win the lottery every year.

 

2008 Hillblom meeting: Morning session 1A

As I said yesterday, today and tomorrow I’ll be attending the annual meeting of the Larry L. Hillblom Foundation.

This morning is devoted to presentations from the leaders and directors of the LLHF’s big “network” and “center” grants, and it appears that a good deal of each speaker’s time will be spent enumerating how many students, fellows, papers, and additional grants they’ve trained, written or garnered over the course of the past year. I’m not expecting very much in the way of data. Still, I’ll try to hit the highlights, mostly from a biogerontology-centric perspective:

• Peter Butler (UCLA) opened his talk with a letter from a parent whose daughter was recently diagnosed with type I diabetes; the author of the letter was distraught about the decrease in quality (and quantity) of life that would result. Pete made the provocative comment that in five years, this letter would be considered “a historical document,” and closed with a confident statement that we’re seeing the “light at the end of the tunnel.”
• Dale Bredesen (Buck Institute) described the mission of the LLHF Center for Integrative Studies of Aging, which opened last year: to bring together scientists with disparate specialties to approach geroscience from multiple angles. He gave credit to prion biologist Stan Prusiner, saying that the organization of Stan’s (gargantuan) laboratory inspired the multidisciplinary approach adopted by the Center. He closed with a quote from Fabricius that struck me as an odd choice during a conference about aging research: “Death comes to all/But great achievements raise a monument/Which shall endure until the sun grows old.”
• Gal Bitan (UCLA) discussed recent progress in creating drugs that inhibit amyloid beta (Aß) oligomerization and toxicity, currently believed to play a major role in the onset of Alzheimer’s disease (AD) pathology. He began with a concise description of the challenge (it’s difficult to use small molecules to prevent protein-protein interactions mediated by very large, flat contact areas) and went on to describe his lab’s efforts to use structural data to rationally design peptide inhibitors. Bitan also reported that his group has developed an efficiacious small molecule drug as well, but he couldn’t tell us more about it because of intellectual property concerns.
• Alberto Hayek and colleagues (UCSD) talked about the challenges of using stem cells to rebuild pancreatic beta cells in vivo. They presented quite a bit of data, but I’m afraid that diabetes + developmental biology = my personal scientific kryptonite, so I got a little bit distracted. The work is very good, I’m sure, and it represents the most likely application of stem cell therapy in large populations in the near-term future.
• Bob Hughes, , Pankaj Kapahi, Simon Melov and Gordon Lithgow (Buck Institute) gave a group talk under the umbrella topic “Chemical biology of aging” (we heard a bit about this at last year’s meeting). Bob introduced a screen for small molecules that extend lifespan in simple model system; the goal is to screen 100,000 compounds, identify drugs that increase longevity in both yeast and worms, and then test these molecules in mice. Pankaj focused on a longevity-related pathway for which small-molecule inhibitors are already known: TOR, which we’ve talked about recently here; he continued with a discussion of differential control of translation during dietary restriction. Simon showed some data from a study of a anti-aging compounds and their effects on mitochondrial oxidative stress in the mouse, and Gordon capped off the hour with data demonstrating a role for endocannabinoids in responding to nutritional status.

Random thought: If a corner café can provide free wireless internet to its customers, shouldn’t a luxury hotel that charges in excess of $200 a night and advertises itself as a venue for “critical corporate summits” also be able to provide the same service for a reasonable price? I just paid $12.95 for 24 hours of what appears to be wireless dialup, or possibly telegraph; blogging is frustrating enough that I feel a little bit like crying. Thus far I am not so impressed by the modern electronic comforts provided by the Balboa Bay Club in Newport Beach — conference organizers, take note.

(Coverage of the morning session continues here.)

*

 

Heading to the Hillblom meeting

This afternoon I’l fly down to Newport Beach for the 2008 meeting of the Larry L. Hillblom Foundation, the kind people who have paid my salary for the past three years. To the extent that it’s possible, I’ll be liveblogging the conference, so watch this space for developments. In the meantime, feel free to check out my notes from last year’s meeting (1 2 3).

If you’re attending the meeting, keep a lookout for this disreputable character, and be sure to introduce yourself and say hi. I’ll be giving a talk about our lab group’s work on Wednesday morning…

…which I should write.