Still Searching for the Holy Grail in the Land of Rattus, Mus and Pan -
or – still wineing [sic] about the aging process

Men dig tons of earth
To find an ounce of gold –
Heraclitus (Fragments)
Sure thing, man. I used to be a laboratory myself once.
Keith Richards (when asked to autograph a fan’s school chemistry book)
There are many people among us who see aging as one of the (last?) great barriers to achieving a greater (higher?) level of human existence; it is seen as “the enemy” that has to be eradicated so that Homo sapiens can finally emerge from its chrysalis and then transform into something magnificent – into a fully-potentialed butterfly that lives forever. Aging is weakness, disability, decline, pain, and suffering. And of course many still equate “it” with the portal – the gateway – to death (which is the ultimate barrier). The linear flow of thought runs like this: aging = morbidity = mortality. Thus, to find a “cure” for aging would break the chain of cause and effect – and perhaps – no maybe, most certainly we would have achieved immortality. And there it is – the Holy Grail of it all. From ancient Chinese Taoism, to medieval alchemy, to the labs of modern science, we are still searching; we are still on the quest to find the elusive and mysterious answer to the riddle that even the Sphinx would ponder and find enigmatic and the core of existence.
And what would be the cure? What elixir would become the magic bullet? What potion would break the chain of mortality? What pill would offset the “mortal coil”? Who can deliver the “fountain of youth” to our doorstep and into our mailbox so that we could experience life unlimited? It could be in the form of some herbal remedy, some mineral compound, perhaps it’s the sweat of virgins, or the testicles of the ox, or perhaps it could be caffeine, or wait, it’s gotta be this synthetic hormone, no wait, it’s this! – Red Wine. Holy sour grapes Batman, wine, of course- and not just the crappy Merlot, get me some of that Pinot Noir. And in our quest for the magic bullet, we test, we alter, we experiment, we measure, we observe the outcomes in our DNA brethren who are manipulated and endure injections, and surgery to solve the riddle.
My purpose in this blog posting is not to debate or contest the use of animals in laboratory research (generally) or in research on aging (specifically). Readers who wish to further pursue this topic may go to (as examples): http://www.apa.org/science/animal2.html or http://www.onlineethics.org/CMS/research/modindex/animalres.aspx or
http://ethics.iit.edu/resources/scientific.html#animal
Rather, my goal in this blog is highlight the way in research on aging “news” is released to the public (and packaged as a “news release”) with sensational headlines but often times very important issues are lost or overlooked or simply denied in all of the publicity and marketing tactics. The science is often perfectly sound and the results credible and the conclusions are typically modest and then balanced with a healthy dose of “limitations.”
Yet, something happens between the presentation at the conference, or the published proceedings, or the publication in the flagship journal – and the delivery of the “news” at various media outlets. I have covered this transformation process before in a previous blog posting, “Lost In Translation: From Neurology to “Party on, Wayne.”
{see http://uofugeron.wordpress.com/2009/01/21/lost-in-translation-from-neurology-to-party-on-wayne/}.
But in this posting I want to reexamine the issue within the context of latest elixir to be promoted as the Holy Grail for an anti-aging “magic bullet” – RESVERATROL
Resveratrol has become volcanic on the “hit parade” in web searches, especially after the 60 Minutes segment that aired on Jan. 26th, 2009 where researchers told Morley Safer that a RED WINE substance (Resveratrol) could one day lengthen lives {see http://www.cbsnews.com/stories/2009/01/25/60minutes/main4752082.shtml?source=mostpop_story}. Not only can you see the video segment there, but I have discovered that almost every company “selling” some variation of Resveratrol had the same video embedded in their internet page(s) where they were advertising their products with disclaimers —- usually posted at the very bottom of the pages like this
“Note: Science is still determining the most effective dosage of resveratrol for humans.”
Or
“Cancers Inhibited by Resveratrol According to Published Research†”
and what does the symbol “†” represent ?
† = In rodents and/or cell culture
And of course there are the convenient “buttons” that will bring you right to the online shopping cart where you can purchase the “magic bullets.”
The actual video segment is interesting not so much for the stunning acknowledgment that a human would have to consume about 1,000 bottles of red wine per day to get the optimal benefits of resveratrol (which certainly sounds like a French Paradox to me – and I would enjoy a good Pinot Noir as well as the next person, but all that massive wine consumption would even make Dionysus think twice)-

But what was interesting to me was the “rat race” – with two mice running on a treadmill and the one with resveratrol getting ready for the Rodent Olympics, while the other one looked like it had run out of gas.
I do not know about you, but I was caught up in the moment (too – like you?), I had just seen the smoking gun! Rat A was kicking the ass of Rat B on the treadmill – now where can I get some of that good stuff. In fact, this new elixir might just help me break my habit of mixing Mountain Dew with Red Bull and Jolt in order to win the “rat race” at work (just kidding – right?)
The other interesting feature within the segment was the portrayals of “skinny” monkeys and “chunky” monkeys in context of caloric restriction diets and that effect on the aging process. Now, I happen to find the caloric restriction strategy to make sense for living life in long lane – the science is there; but excuse me – when the segment then went to a party with the “skinnys”- people who were into hypermode with caloric restriction – I was initially shocked at the appearance of the party-goers. At first, I thought they accidentally slipped in a video clip for adult manifestations of Anorexia nervosa. I was on the verge of walking out to my truck and heading down to KFC and tanking up on some mashed taters with extra gravy – and throw is some more biscuits will ya?
But one thing we might have missed in the video segments: It’s all (still) research results on and from Rattus, Mus, and Pan, and the leap to Homo sapiens is still just that – a leap. The GENERALIZABILITY OF RESULTS is a huge factor here. But too late – the gates have opened up and the media has taken off chasing the rabbit – once again. The “news” that the results were limited to animals – and that it will be years before “empirical evidence” using scientific controls and studies on humans – can once and for all prove that we have the magic bullet in hand. And in any case, we are still back to this:
So, by reducing caloric-intake and popping some capsules of resveratrol, I can live longer? Okay, then what? What do I do with the longer amount of time?
More shopping? More golf?
And therein lies the true riddle of the Sphinx – or better yet the strangeness of Zeno’s paradox: “In a race, the quickest runner can never overtake the slowest, since the pursuer must first reach the point whence the pursued started, so that the slower must always hold a lead.” Here is my question and concern as it relates to the quest for conquering the aging process:
If you were to live ten more years than expected –then what?
If you were live twenty-five years more than expected – then what?
If you were t live another hundred years than expected – then what?
What does change then? – if not for the fact that you have extended time. Well, there is more possibility and potential – and experience – and avoid, if at all possible – oblivion or what Shakespeare (via Hamlet) would refer to as “the undiscovered country” – the great unknown, which has been graphically “known” by others such as Dante via The Divine Comedy. But to think and know and feel that it would all be washed away as an antiquated event of the past – to what was in the “old days” to what is now possible: A new beginning, a fresh new frontier on the horizon where both aging and death are dispatched to the history books. Go science – go! Deliver us from all pain and suffering. Where do I sign up?
But really, truthfully, what changes? If one’s life was simply more of the same – only extended out further –and then forever, with the same “Groundhog Day” effect, for many this would soon resemble some Kafka novel where the blessing would twist into a curse, and the promise of paradise soon would become a living hell. Thus, my concern that the pursuit of the number – the increased age – the longevity addiction – the immortality quest – is what simply fogs up the counterweight of the PRESENT – and the MOMENT – and the experience that is the quintessence of life – which is no matter how long you live, what matter is the life – you give to life – for one minute or for a day or a year in a lifetime. In the eternal pursuit of the philosopher’s stone upon this earth, we have become distracted from quality of the moment – and to what makes the difference whether we live in some specified block of time deemed to be “short” “enough” “exceptional” – whether that is 25 years or 250 years.
In the book, Meditations – from the emperor/philosopher Marcus Aurelius, there is the blunt wisdom that makes one reflect upon the search and the struggle for wanting to overcome aging and mortality –
Our lifetime is so brief. And to live it out in these circumstances, among these people, in this body? Nothing to get excited about. Consider the abyss of time past, the infinite future. Three days of life or three generations, what’s the difference?
But that advice, that wisdom, is all but lost in our modern WAR ON AGING. Yes, a war on aging – and the first shot is directed against the philosophy of Marcus Aurelius because he lived in the Roman era of a short life span and thus, the Meditations are seen as “fossil-like”- interesting aphorisms trapped in amber. But my colleagues in the domain of bio-gerontology missed the point and the crux of his sayings.
On one level I am in agreement with my colleagues in this regard:
Why We Need a War on Aging
Based on presentation given at 2009 World Economic Forum in the Live Long and Prosper session, January 28, 2009 by Professor Julian Savulescu.
{http://www.practicalethicsnews.com/practicalethics/2009/01/why-we-need-a-war-on-aging.html}
“The goal should be to extend the HEALTHY, PRODUCTIVE lifespan, not to just keep people alive longer on respirators or in old people’s homes. This is embodied in the concept not of life span but “health span”. The easiest way to do this is to prolong healthy life not attempt to compress morbidity.”
And my colleagues do address the “objections” to everyone living longer (within our finite ecological system, known as “earth”). I respect their points, but do not necessarily agree with their logic – or examples:
“We have an obligation to die and turn the world over to the next generation.”
“How long each generation should live raises deep questions about intergenerational relations, quality of life and burden of care. However healthy and able older people may be economically productive, self supporting and a source of knowledge, experience and care for younger generations, liberating younger people to work. The answers are not clear, especially when life extension is coupled with life enhancement. At any rate, since few of us believe there is a positive moral obligation to have children, that is to create future people, the obligation to create new generations must be weak.”
Meaning in Life? – “Many people fear that a longer life would result in boredom and a gradual loss of meaning. This would be more likely if one was a solitary Methuselah. But in a world where many of those close to us also lived longer, the greatest source of human well-being – deep human relations – would remain intact and arguably grow richer as that network expanded across generations.
“There is little empirical support that longer good life loses meaning. Research shows that life-satisfaction remains relatively stable into old age. One survey of 60,000 adults from 40 nations discovered a slight upward trend in life-satisfaction from the 20s to the 80s in age. With the advent of human enhancement– enhancement of cognitive powers, physical abilities and control of mood – this is likely to be even less of a problem.
“The challenge is to create longer and better life. But that too is within our grasp. We should aim for drugs to prevent normal memory decline, interventions to keep us physically and mentally active. Viagra is a good example. It deals with one effect normal human aging. 20 million men in the US find it of benefit and it no doubt contributes to meaning in their lives in some way.
And surely it is up to individuals to decide whether their lives come to lack meaning. For our part, we would take the longer life. Our goal should be more, much more, longer and better life. We need a war on aging.”
Where I disagree – or take issue – is this dimension:
While I appreciate their focus on the balance of outcomes = “longer and better” and “healthspan” versus “lifespan” – I remain skeptical about the so-called balanced focus in this quest. I see more about emphasis on “longer”(quantitative) than the “better” (qualitative) – and it is does not increase my confidence level any when the proponents of the war on aging simply shrug their shoulders with the caveat of “it is up to individuals to decide their lives come to lack to meaning.”
This is a classic example of science creating a firewall with its goals (and research) while hoping that other aspect of humanity (culture, religion, art, humanities, philosophy) will rush in to fill the void of “meaning.” Guess what? for many people (and or better or for worse) science is the “religion.” And if Viagra is an example of what science can do to “give meaning” to our lives (or is that only for men?) – then I propose we have allowed Erectile Dysfunction (ED) to trump Existential Dysfunction (ED) into the later years of life.
Terms like “human enhancement” sound too vague and ambiguous to me, especially with the notion of the “control of mood.” This almost sounds like that the answer to the “meaning of it all” is to be found in the daily dosage of SSRIs – or have we not read this in a Hollywood script for a movie once before? I am very much for the medical and psycho-therapeutic treatment of clinical depression and anxiety disorders, but to put all of our stock into drugs (see Keith Richards pun-intended line at the beginning of this blog) as the key toward “fulfillment” with longer years of life sounds remarkably hollow and about as authentic as saccharin in my coffee – hyper-sweetness with a troubling aftertaste – and doubly ironic as saccharin has an interesting history with lab rats in terms of “causing” certain cancers (notice the “non-connection” to humans).
So, while we seek the Holy Grail of the aging process within animal models, I hope that in our quest (and focused determination) of the one thing (living longer) we do not leave it up to chance or accident or individual “choice” to acquire the other thing (living better).
“Living better” is not something to be bought or created in the lab or ingested like Skittles candy –
Living “better” may not even be the other side of the coin. Better than what? Better from what?
I am convinced that if we – as a society – do not address these issue of the morality and ethics and the purpose and the duties and the responsibilities in a more in depth way in the context of living longer, we will inherit The Waste Land –
We will have defeated the CHRONOS – and perhaps will have lost the KAIROS.
Perhaps with our Pyrrhic victory, we will then see and learn from the way that it was – in the past, in the old days, when death instilled meaning by having us LIVE each moment as though it were the last. Living forever – the infinite – is not exactly a soothing thought to contemplate, just thinking about it stretches the mind – like Tom Stoppard’s quip with Infinity a “…a terrible thought…where’s it all going to end?” (Stoppard, Tom, Rosencrantz and Guildenstern Are Dead, Act 2, Faber, London, 1967).
Some have taken the bet – better to live longer and perhaps forever. The logic might be that one has “forever” to figure it all out” – and so what’s the rush? Foreverness is the answer and procrastination is the question.
If I had forever, would I have even written this blog posting contemplating the “it”?
Or did the fact that you took the chance to read my blog posting and made it this far – give you the impression that my writings seem like the “forever?”
(just a little blogging humor to end with….
– or does my desire to blog
never
end?…………………………………………………………………………………………………..
Now, if they figure out that a cold Modelo and some Sauza Tres Generaciones Anejo (tequila) can help you live longer – I’m there –
thanks – Scott D. Wright
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Detailed Postscript (very optional)
First, let me say the biological logic of continuity for using “animal models” for research on aging has its rational merits; yet what I am most skeptical about – are the huge leaps in to the premature generalizations to Homo sapiens from the results/outcomes. I want to give the scientisits that benefit of the doubt that they qualify their results and state the limitations, but that does not stop the “publicity machines” form wanting something more. I can almost hear the writers in the marketing division saying ,”Yeah, yeah, yeah, nice, but what does it all mean? Rats and mice don’t read newspapers or web sites; what about our readers (human)? and potential donors? – and of course, the general public? They want to know we aren’t just screwing around over here. Give me something to work with here. What about this? “Red Wine – Just what the Doctor Ordered” or “Those crazy French were right after all”. We all need to read the fine print with both research and with the “shopping cart” before we hand over our money and our critical thinking.
Other sources and info -
Michela Gallagher, and Peter R. Rapp published an informative piece in the Annual Review of Psychology, Vol. 48: 339-370 (Volume publication date February 1997) – THE USE OF ANIMAL MODELS TO STUDY THE EFFECTS OF AGING ON COGNITION – and they addressed the importance of animal models for understanding the effects of normal aging on the brain and cognitive functions; 1) studies of laboratory animals can help to distinguish between healthy aging and pathological conditions that may contribute to cognitive decline late in life; 2) research on individual differences in aging, a theme of interest in studies of elderly human beings, can be advanced by the experimental control afforded in the use of animal models.
Richard L. Sprott and Israel Ramirez (1997) in the LAR Journal V38(3) – Animal Models of Aging Research: Current Inbred and Hybrid Rat and Mouse Models, have offered these justifications:
Animal models are commonly used in aging research because they allow researchers to obtain data that are difficult or impossible to obtain from humans. Some studies that can, in principle, be done in humans are much easier to do in animals because of their shorter life spans. For example, measurements of changes over entire life spans, which would take many decades to complete in humans, can be accomplished in rodents in 2 to 3 years. Other kinds of experiments cannot, even in principle, be done with humans. Using rodents, researchers can manipulate breeding, extract tissues, administer bioactive agents, control diets, and perform surgical manipulations–procedures that would be unethical or excessively hazardous using humans.
And then this from another web site: http://websites.afar.org/site/PageServer?pagename=IA_expert_Austad
“The question remains, however, whether human aging can ever be fully understood by studying organisms that (1) are not long-lived to begin with and (2) are several hundred generations removed from life in normal wild conditions. It is this question that inspires Steven Austad, a professor at the Barshop Institute for Longevity and Aging Studies and the Department of Cellular and Structural Biology, University of Texas Health Science Center, to include a variety of non-traditional animals in his research into the aging process.
Dr. Austad participated recently in the Why We Age scientist-luncheon series organized by the American Federation for Aging Research. His presentation at the event focused on what the natural world can teach us about improving health and extending life. Here, Dr. Austad talks to Infoaging in more detail about this theme and what the near future of aging research may reveal.
Infoaging: Due to practical, clinical or regulatory issues, non-primate animal models have become one of the most important tools of aging researchers. What animals are traditionally used in aging research? Why are they chosen?
Dr. Austad: “The main animals that are used include Caenorhabditis elegans, a roundworm found in soil, fruit flies, and mice. They account for more than 95 percent of papers on aging research, mainly because we know so much about their genetics and how they develop. They are also very short-lived, even for the group that they’re in. Caenorhabditis elegans, for example, is short-lived by worm standards. And fruit flies are short-lived by fly standards, and mice are short-lived by mammalian standards. This is important because in a certain type of aging research, scientists follow an animal through its whole lifetime to discover clues about the aging process.”
Interestingly, the prevalence of mice in aging research is really a historical accident. In the 1920s, the fancy mice kept by hobbyists were discovered to get lots and lots of cancers, which made them ideal subjects for cancer research. As they got used more and more in biomedical research, they became extremely well characterized. Eventually, they supplanted rats as the mammal of choice in aging research. Rats were useful because they had bigger organs — bigger hearts and bigger brains — that were easier to manipulate in certain laboratory techniques. We’re now so successful at miniaturization that it’s no longer necessary to start with large tissue samples.”