Monday, July 4, 2011

Can Aging Be Reversed?

Jeanne Calment (1875-1997) lived 122 years in Arles, France, and died as the oldest documented person. Reporters would often ask her to what she attributed her surprising health and longevity, and her answers varied. She smoked (probably lightly) until she was over 100.

Can aging be slowed, arrested or reversed? This was the fascinating topic addressed by Dr. Thomas Rando of Stanford University at the Aspen Ideas Festival on Sunday. In a highly entertaining talk, he gave us reason to believe that there could be affirmative answers to each of these questions.

Aging versus Longevity

First, some distinctions. Aging is a process, which is not really measurable. Right now, we do not have a biomarker that tells us how old or aged a cell is. Consequently, we cannot measure how fast or slow someone is aging by looking at their cells or tissues.

Longevity, on the other hand, is eminently measurable, since it is simply elapsed time. Human life expectancy at any one time is defined at the age at which 50% of people die. The 1970 curve for life expectancy in the US tells us that 50% of people born in 1900 die at age 70. This curve is convex, unlike the curve for animals in the wild, which would be concave. In other words, most animals in the wild die earlier, with a long tail of survivors, while most humans survive with a more gradual falling off.

Life expectancy improved dramatically in the 20th Century. The 1900 curve exhibits a life expectancy of about 45 years, in large part due to a drop in infant mortality. The 2010 curve shows 80 years, as health gains continue into the 21st Century.

The Genetics of Lifespan

It is remarkable that there is a 100,000-fold difference in longevity between the shortest- and the longest-lived species. Mayflies live for less than a day, while a giant tortoise can live 200 years. There is also a slightly odd relationship between size and longevity. Larger species tend to live longer, yet within a species, smaller subspecies tend to live longer, e.g., consider different breeds of dog.

Furthermore, studies of model organisms (such as flies, worms, and mice) in laboratories have shown that mutation in a single gene can extend life. So one might ask: why do sexually mature individuals begin to age almost immediately? Why don’t they simply maintain themselves at a prime level of health? And what evolutionary processes are involved with aging?

Slowing or arresting aging

With regard to slowing down the aging process, we know that lab animals live longer if they are given fewer calories, but get adequate nutrition. The Caloric Restriction Society advocates this for humans, although there is as yet no scientific proof that such a regime is effective. Caloric reduction at levels that make a difference will increase feelings of hunger and cold.

The arresting of aging has been observed in certain animals that assume a state of suspended animation when conditions are unfavorable. E.g., worms go into what is called a Dauer state, like hibernation, when the environment is challenging, emerging later without have expended lifespan in the process. 2000-year-old seeds have been found at excavations and subsequently been coaxed into supporting plant growth.

As with caloric reduction, hibernation is not a very attractive option for humans in the normal run of things. (Space flight and sitting out a few centuries of radioactive contamination suggest themselves as appropriate circumstances for doing this.) Meanwhile, pharmaceutical research is looking to understand the effective mechanisms behind caloric reduction and find a way to deliver the benefits in a pill.

Reversing aging

Skeletal muscle is apparently a good place to start when looking at the effects of aging. Young muscle makes new tissue in response to injury, but with age there is atrophy of individual fibers and a general loss of condition. Consequently there is impaired regenerative myogenesis, i.e., less striation and increased tissue fibrosis (scarring) in healing.

The question is: why don’t older people heal? They haven’t run out of stem cells. It’s as if their stem cells are ‘asleep’ and don’t ‘wake up’ when needed. Experiments have shown that stem cells can be activated if the signaling pathway is enhanced by additional molecules.

In a key experiment, known as parabiosis, mice are paired surgically, literally joined together so that they form a shared circulatory system. If you have both young and old mice, you can join like mice together (i.e., young+young and old+old) which is called isochronic parabiosis, or you can join unlike mice (i.e., young+old) which is heterochronic. You leave them together for months and look at re-striation in response to injury in paired mice.

The sort story is that isochronic pairs show no change in their ability to heal. The young do well and the old do less well. But the heterochronic pairs do well, as if the young half of the pair has somehow reset the old. This result holds good for every kind of tissue that has been looked at so far.

Leaving aside the grisly possibility of yoking young and old humans together, can the aging clock we reset by some other means? Obviously, cells can be reset. For example, fertilization of an egg resets the clock by making old cells young again, and a similar effect is seen in cloning. This kind of cell ‘reprogramming’ is usually accompanied by dedifferentiation, i.e., differentiated sperm and egg cells become undifferentiated again to an earlier stage of development. Yet, in the parabiosis experiment, exposing old cells to a younger environment ‘rejuvenates’ them without dedifferentiation.


This research is aimed primarily at healing older people heal, rather than extending their lives. Nevertheless, the results are suggestive of means by which aging could be reversed. One wonders if some combination of slowing and reversing could indeed extend life, should pharmacological means become available.

There were very many questions after this talk, but the main takeaway for me was the caution that Americans risk losing life expectancy in the current obesity epidemic. Could this generation really be the first to lose ground instead of gain? That would be a strange biological parallel to the current dwindling of the American Dream.

Saturday, July 2, 2011

Aspen Ideas Festival - Highlights

Liaquat Ahamed’s talk on "The Lords of Finance" began with a tour of some colorful characters of the early 20th Century world of banking, but quickly morphed into an insightful comparison of the 1929 stock market crash with more recent woes. The two bubbles show many similarities (e.g., overly easy credit leading to overborrowing) and some differences (an imminent sense of doom in the 1920s, versus financial hubris in the run up to 2008-2009).

But the main contrast is between how the US government handled the banking crisis once the bubble burst. In the aftermath of 1929, banks were allowed to fail, budget deficits were avoided, and interest rates were allowed to rise. Say what you like about Paulson, Geithner and Bernanke, but they did not repeat the mistakes of the 1930s. The stock market may have fallen a comparable 50% or so, but the recent crash was not accompanied by 25% unemployment. Ahamed attributes the avoidance of this outcome to the well-known bank bailouts, stimulus packages and interest rates controls, and it’s hard to disagree.

At the end of question time, Ahamed introduced the sobering idea that we are about to enter a ‘lost decade.’ In other words, growth and stability will have to give way to significant changes in both our economic and social arrangements. If found it easy to believe that this is so, and that the 2010s could join the 1930s and the 1970s in history as a time of more or less painful adjustment.

The full title of this session with Thomas Friedman (and his latest book) is “That Used To Be Us: How America Lost Its Way in the World It Invented and How We Come Back.” The leading phrase is taken from a speech by President Obama concerning economic progress in China (better rail system and the fastest supercomputer). The interview was conducted by Walter Isaacson of president and CEO of The Aspen Institute.

Friedman began by talking about the American Dream, and how “its future is now in play.” Americans can no longer assume that each generation will be better off than the one before, while our deteriorating infrastructure suggests things may actually get worse. He sees the possibility of a slow decline, and worries that Americans are getting used to second best.

According to Friedman, America’s past success was rooted in a public/private partnership with sensible policies around education, immigration, infrastructure, risk/capital management, and scientific research. Each of these five pillars now seems to be crumbling. Further, the US has “declared war on math and physics” by turning a blind eye to financial legerdemain and climate change. Markets and Mother Nature will correct us, if we don’t correct ourselves, and it won’t be pretty.

Robert Rubin, co-chairman of the Council on Foreign Relations and formerly of the Clinton administration, was interviewed by Chrystia Freeland of Thomson Reuters. Rubin stated that the US is at a ‘historic crossroads’ and that the ultimate challenge is political, not technical. Washington needs to address the debt crisis, finance public investment, and reform education and healthcare, but ideology and opinion are getting in the way of facts and analysis, and the media isn’t helping much.

At question time, Rubin said he was ‘really worried’ about the current impasse over the debt ceiling, and thought the situation was ‘horrendously risky.’ Making the debate about debt a debate solely about spending, is completely wrong, in his view. If the deficit is greater than discretionary spending, how can you cut your way to a balanced budget? The issues have not been framed properly, and there is no sensible discussion. I find it hard to disagree.

Like Tom Friedland, Robert Rubin ended by saying that he was optimistic. Both cited the basic strengths of the American people as the source of their optimism, despite having decried a certain level of ignorance in the electorate. One wonders if polarization is going away any time soon, given the ‘echo chamber’ effect of both traditional and social media, whereby people’s selection, sharing, and curation habits tend to reinforce their own deeply held beliefs.

More reviews can be found at the AIF blog and the Thomson Reuters blog.

Monday, February 7, 2011

Strata Conference on Big Data: Talking Points

Two presentation got my attention at this two-day meeting.

Benjamin Black of fast_ip described attempts to build a huge store to collect, index and query trillions of records involving multi-dimensional data. A typical application might be running analytics over huge amounts of sensor network output, where the events of interest have many attributes. The challenge is to manage write performance in the loading of data and the number of key fetches needed to generate query results.

Speedy response to multi-dimensional queries is really an OLAP (Online Analytical Processing) problem, which has been well-studied in the literature. The trick is to precompute many of the results in a hypercube that materializes the most important data relationships. Such an approach finally enabled them to perform most queries quickly within the database, instead of dragging data, kicking and screaming, to the computational engine.

Werner Vogels (CTO, Amazon) defined data as ‘big’ when you have to innovate to collect, store, organize, analyze and share it. Certainly, the Amazons, Googles, Yahoos, and Facebooks of this world were forced to invent their own solutions to the problems posed by their burgeoning businesses. Conventional database vendors, such as Oracle and IBM, were in no position to support the volumes or velocities of true Web scale.

Vogels’ talk focused primarily upon Amazon Web Services and Elastic MapReduce, which affords any business the ability to run big data on Hadoop. Bringing data to the cloud allows for faster and more flexible processing than most businesses could achieve on their own. Apparently Fedexing disks is as good a way as any of delivering the data, and better than sending it down the wires!

Clients such as Best Buy, Yelp and Etsy run between 100 gigabytes and a terabyte or so of behavioral data through AWS every day. As Amazon’s Jinesh Varia pointed out in a later talk, this is way more cost-effective than buying your own servers and SAN storage. In addition to loading raw data, you can index the aggregated records in parallel, so that execs can query the resultant database and geeks can be constantly running experiments.

Tuesday, December 28, 2010

That Synching Feeling

I spent the holidays wrestling with mobile devices, and came to the conclusion that pretty much all the current offerings are unsatisfactory. Budget laptops weigh and cost about the same as a Winchester rifle, but are far less pleasing to own. iPads are fun, but you'll have to work if you want to import content except via the Company Store (a.k.a. iTunes).

The Android tablet I got from some points program is a nice toy and features (gasp) a USB port for easy content ingestion, but the software isn't going to meet anyone's business needs. I'm waiting for Playbook before I buy any more tablet style devices. The netbook is a nice idea, but I think getting the balance right between what's local and what's in the cloud is really hard.

I’m hoping that open platforms will give me greater access to content and functionality I’ve already paid for, but I’m not holding my breath. I remember once standing on a pontoon in Pearl Harbor and gazing down into the waters at the barely discernible shape of a dead battleship. So many hardware and software platforms end up looking like this.

Tuesday, June 1, 2010

Steve Jobs at All Things Digital

I liked the opening music: "Got to Get You into My Life" from the Beatles seemed appropriate as the iPad hit 2M sales worldwide.

Walt Mossberg and Kara Swisher presiding; the session got off to a slow start. Initial question about Apple's market cap. Steve: "It's surreal", but it's not what gets him out of bed in the morning. Flash? Apple made a call; no-one currently provides flash on smartphones, and anyway HTML5 is the future. Walt tugged at my heartstrings momentarily by pointing out that Picnik (the wonderful photo editing tool) is a Flash app, but Steve maintained that many Flash apps are ads, and that "the hole is getting plugged real fast." (My favorite guitarist's web site is pretty much all Flash.) Moderators initiated more excursions into stories like the stolen iPhone and Foxconn suicides, but finally we get to the good stuff.

(1) Platform wars. Steve: we don't see it that way. Google "decided to compete with us" in the phone market. ("We didn't go into the search business!") iPhone was the first time carriers were told to just manage the network, while we handled the apps. He pointed out that AT&T (despite all the flak they are catching from users) "took a big leap" with Apple when they changed the rules of the game.

(2) The Tablet. Steve: we reimagined the tablet, without handwriting. "If you need a stylus, you've already failed." The multi-touch glass display actually began in-house as a tablet project, then migrated to the phone. Will the tablet save journalism? Steve: we need editorial more than ever right now. His advice to online newspapers: "Price aggressively [ie., cheaply], and go for volume."

(3) Future of the PC. Steve: PCs are a bit like trucks. Not everyone needs one nowadays, because we are no longer an agrarian society. The iPad is a magical device that has just the right blend of features for most people, and we have only just scratched the surface with apps. Software will get more powerful, and the bluetooth keyboard can be used when you want to create or edit content.

(4) Content curation. Walt: what about controversies re control of content on your devices. Steve: We have open and a curated platforms. We support the open standard of HTML5 better than anyone else. But we also provide the App store, where we disallow apps that crash, or don't function as advertized, or use unsupported APIs. We approve 95% of apps submitted within 7 days. We don't allow apps that defame people, but we took a couple of iterations to get that right, e.g., political cartoons.

(5) Kara: What do you do all day? Steve: "what I do all day is meet with teams of people." Kara: Do you win all the arguments? Steve: "No, the best ideas have to win!" Otherwise how could you attract and retain really good people? We have the same values now that we had back then, namely "build the best products for people." Why are you going into the ad business? So that developers can make money on their apps. We need to put this into the OS, not over and over into the apps themselves.

(6) Privacy. Steve: we worry about location in phones. We make apps ask the user if they want their location made available. We turn down apps that want to suck all your data into the cloud. We were "pissed off" at Flurry who used apps to track devices at Apple's Cupertino campus. We changed our TOS so that apps can't sell your data to analytics firms. At the very least, they should ask the user before sharing that information with third parties.

(7) Question time: record companies and television. Steve: record companies thought Tower Records and Best Buy were their customers! The front end of the business had to change, and marketing is now better and cheaper (direct to the customer). The problem with TV is the go-to-market strategy. People are used to getting set top boxes for free, which kills innovation. No-one wants to pay for another box, so the whole thing needs a redesign from scratch. Until then, AppleTV is just a hobby for us.

This was a wonderful opener, whose spirit I can't really capture here. You had the impression of a great mind being unflinchingly honest and not afraid to express deeply felt beliefs. (OK, so I'm a fan, sue me.) Yes, the Flash thing is a nuisance, and Apple's culture probably isn't the paradise that it's portrayed to be (what corp is?), but these guys are among the few who really know how to bring great products to market. Being at the session was worth the price of admission, as far as I was concerned.

Monday, May 31, 2010

Spring Conferences, Part 3

SIIA NetGain was a one-day meeting in San Francisco this year, followed by a one-day field trip to Adobe, Google and Apple campuses. I will only cover the highlights here.

Ann Michaels chaired a good panel on social networking with Johna Burke (BurrellesLuce), Tabrez Syed (Spiceworks) and Serena Wellen (Lexis-Nexis). Most interesting segment was on Lexis-Nexis Communities and Martindale-Hubble Connect. Communities is an open networks that combines free and fee-based content currently aimed at 28 communities, some of which are practice-based (such as bankruptcy and insurance) and some of which are role-based (associates and paralegals). The content mix contains news, blogs, podcasts, video and ads. MH Connect is a closed referral network with multiple subscription levels, including free, built on top of an existing attorney directory. L-N gets content from contributors, who are also their customers, and monitors the spending of members in other parts of the business. The idea is that subject matter experts who generate content drive the visiting and viewing behavior of the larger population, providing revenue opportunities.

Andy Weissberg of Bowker chaired a panel on "How E-Readers Are Changing the Publishing Game" with Colin Crawford of Media7 and and Miles McNamee of Copyright Clearance Center (CCC). There was some discussion of how music went from paid analog (legal) to free digital (illegal) and to subscription digital (legal). Obviously there are some parallels to the book business, in that getting quickly to a convenient and affordable service model is in everyone's long term interest. But publishers now need to worry about the pirating of customers, even if the content ownership issue is settled. Customers, and the data they provide, are an important (if neglected) asset of publishing companies, and right now neither Apple nor Amazon is sharing customer data with content owners. (Google has no plans to do so either, as we discovered later in the context of Google Editions.)

Ken Doctor chaired a panel on "News Start-Ups" with Robert Rosenthal of the Center for Investogative Reporting and Jonathan Weber of the Bay Citizen. I found the idea of start-ups getting into the turbulent news business a little odd, until I realized that CIR is a non-profit, and the Citizen plans a public radio style business model of sponsorships and grants from foundations. Both plan to experiment with new business models, including ads and subscriptions, in order to sustain real journalism, as opposed to op-ed style blogging. CIR plans to move to video, in search of "more CPMs", though one wonders if they understand the cost structure of shooting and storing large amounts of rich media content, or the fact that even Google's highly efficient CPC model is unable to fully pay for their YouTube portal. (CPM on highly popular Facebook is a mere $1, compared to AdSense's $25.)

I may write about the Adobe and Google visits later; I jumped ship at Google and didn't proceed to the Apple campus.

Spring Conferences, Part 2

The New Directions in Text Analysis conference at Harvard was an eclectic gathering that mixed social scientists and computer scientists interested in tools for mining or otherwise taming large amounts of text. I will only describe a handful of the papers here.

The conference began with a technical paper about statistictical tools for data driven science policy decisions by Hanna Wallach of UMass that focused on Latent Dirichlet Allocation for topic models. A topic is operationalized as a specialized probability distribution over all the words in the vocabulary. Documents can be considered as the product of an underlying generative model that may have hidden structure, and whose parameters must be learned from observables by statistical inference.

Lars Backstrom of Facebook gave an interesting paper about memes: topical text fragments that persist through many articles. He described a graphical model that represents quotes and misquotes as nodes linked by weighted edges, the weights depending upon repetition and edit distance between the corresponding strings. The graph can be partitioned into memes by deleting low-weight edges (NP hard, but can be managed with heuristics). See the MemeTracker web site for more details.

Jure Leskovec of Stanford's paper looked at influence and dynamics in online media, especially the interplay between mainstream media (MSM) and the blogosphere. Different memes seem to have different temporal signatures, depending on where they originate and who adopts them. Most big stories break in MSM and are then taken up by blogs; a lesser number break in the blogosphere and are taken up by MSM. The time/volume graphs of these events look quite different when you control for scale and duration.

Does bad news travel fast, or at any rate faster than good news? Previous research by Berger and Milkman on NYT articles suggested not. The paper by Michael Macy of Cornell presented a data mining study of Twitter that showed that positive affect dominates all forms of tweet. Furthermore, a study of half a billion US tweets showed that certain words have a pronounced diurnal rhythm when you adjust for time zones, including some words you might expect ("coffee") and words you might not expect ("random").

All in all, a worthwhile meeting that also showcased some Harvard research into such topics as data visualization, Chinese history and Japanese politics. I gave a talk on 15 years of R&D at Thomson Reuters that shared some of the things we have learned along the way about text analytics, machine learning, and user data.