To Your Good Health and Longevity

November 9, 2003

11/9/2003 Update:
    This article on the Life Extension Foundation website presents two additional possible approaches to slowing the aging rate. One of these, involving Ames and Snell dwarf mice points to an effect that, although modest, might afford  an independent means of slowing the rate of aging.
    Most aging research has been focused on short-lived organisms whose lifespans would fall within a graduate student's tenure in graduate school. Only recently have long-lived animals been investigated in detail, primarily because of the efforts of John C. Guerin. We're now learning that many animals have longer lifespans than humans, and among these are rockfish (Pacific perch). As Mr. Guerin's linked table shows, different species of rockfish have lifespans ranging from about 12 years for the Calico rockfish to at least 205 years for the Rougheye rockfish. The fact that different species of the same genus have such dramatically different lifespans hints to me that not very many genes are involved in setting the lifespans of these rockfish.
    One question that comes to mind is that of the metabolic rates and rates of energy expenditures of these rockfish. I picture a rockfish hiding in a hole or crevice in a pile of rocks where it is relatively safe from predators. If it doesn't have to move around for its food, it might be relatively exempt from the tooth-and-claw struggle of other sea creatures. Under these circumstances, it might more or less hibernate, burning calories at a very slow rate. There are indications that there is negligible senescence, with no rise in mortality rate or other tangible changes between young rockfish and centenarian rockfish. However, initial studies of hepatocytes have indicated an increase in lipofuscins with age.
    Most organisms consume the same number of calories per kilogram over the course of a lifetime, but birds, bats, humans, and other species are exceptions. Birds and bats burn through about four times as many calories as mice, dogs, and horses. Humans weigh the same as chimpanzees and yet, live about twice as long as chimps. One of the key questions about rockfish and other especially long-lived species will be: how many calories do they metabolize per unit body weight in the course of a lifetime?

This article, Red Sea Urchins Found To Live Up To 200 Years - Science Daily, appeared on Friday.

A Word from Your Canary
     Over the years, I've tried a few touted remedies for aging. None of them have ever worked... until now. Even now, the possible benefits are, so far, entirely subjective. I'm almost afraid to mention them for fear of raising your hopes and then dashing them into the dirt again, so please regard what I'm about to say as highly tentative and unconfirmed. 
    I seem to be wonderfully energetic and upbeat. (Picture a jolly Irishman on Prozac!) I might suppose this to be something akin to a "caffeine high", but it doesn't fall away after a few hours like caffeine, nor is there a rebound from it. If I haven't had enough sleep, I'm sleepy and tired, but I still have energy left over This is consistent with Dr. Treadwell's remarks yesterday:
    "I can tell you that I have followed over 50 people very closely for almost 4 years and in general the positive effects continue.  The most common remark is most people feel happier, more positive attitude, and a general feeling of well-being.  Other comments are increased energy and strength."
    I also found and reviewed Dr. Ames' presentation at the 10th Congress of the International Association of Biomedical Gerontology, and they make it clear that this enhanced energy is a concomitant of a "mitochondrial tune-up" at an intracellular level. That makes the feelings rather remarkable in that it seems to me to be unusual to have systematic be evident so quickly. Of course, it takes a while to turn green and grow a tail, so we'll have to wait and see.
    I feel sufficiently comfortable with this conclusion that I'm bringing Tommie in on it.
    The talks and slides given at the 10th Congress of the International Association of Biomedical Gerontology, convened at Cambridge, England 19-23, September, are available over the Internet.   Ames  Slides   
    Incidentally, Tommie is feeling dizzy lately after taking our supplements. Her dizziness disappears when she abandons the supplements for a couple of days. She isn't taking Huperzine-A so that can't be it. We're going to back off to a multivitamin tablet and a few dietary manipulations like fish twice a week and then add supplements back one by one until we identify the culprit.
    We'll see after I've been on the full dose of ALC and ALA a little longer (you know...  to turn green and grow a tail), but so far, the results are upbeat.

The Meaning of an Effective, Practical Age-Slowing Technique
    I've said it before and I'll say it again, the implications of a certified means of slowing the rate of aging would, I believe, be profound. 
    In a sense, we might say, "Either it works or it doesn't." There could be degrees of success, but if resveratrol slows our rates of aging to 70% or 75% of what they are now, then it will have worked. And even if it doesn't, this is history in the making. Other palliations will follow in brisk succession.
    Dr. Roy Walford, in his latest book, "Beyond the The 120-Year Diet" lists a set of tests that can be used to arrive at someone's physiological age, and to determine whether a caloric-restricted diet is actually slowing your rate of aging. Presumably, these markers can be used to tell whether resveratrol is achieving the same goal.
    To me, the most important part of the retardation, and ultimately, the conquest of aging is be the matter of holding at bay cancer, cardiovascular disease, cognitive impairment, Parkinson's Disease, and other diseases that dog the footsteps of "mature citizens. You won't find many people, young or old, who want to die of one of these maladies.
    If we can buy time, improvements should be coming faster and faster.
    The conquest of aging is in a league with space flight and computer technology. The researchers who are involved in it and those of us who read about it are probably looking at the here and now with our eyes upon the path just before us, but what they're  doing will reverberate down through ages to come  They 'e making history, and, viewed from the future, they will be seen in history's rear-view mirror as glamorous figures who lit up crannies of darkness. 

Beware of Rexall Sundown?
    A few years ago, a pharmacist friend of ours warned against buying vitamins and nutritional supplements sold by Sundown. He said that their products didn't live up to their claimed lists of ingredients. I took him at his word and switched to Spring Valley, available at Walmart. Tonight, exploring Spring Valley on the Internet, I discovered that Spring Valley is a subsidiary of Sundown, that Sundown has renamed itself Rexall Sundown, that there are divers Federal Trade Commission, class action, and Food and Drug Administration actions that have been taken or are still pending, that Rexall Sundown, et al, was bought out by the same Dutch company that bought out General Nutrition, and so forth.
    Below are some of the articles that I found regarding Rexall Sundown/Spring Valley/Unicity/Showcase International/....  You may recall that Enron had a number of shadow corporations that helped mask what was going on in the company.
    It sounds tome as though if a graft gets big enough, it's above the law. 

Rexall Sundown to Pay up to $12 Million to Settle Charges ...
Rexall Hit for Deceptive Marketing of Calcium Supplements
Courts preliminarily approves Rexall lawsuit - 2003-06-17 - The ...
Rexall's rotten eCommerce example
Recall Update- Rexall Sundown Fish Oil Recall is Complete
Rexall distributors! Network Marketing Made Easy For You!
Business Professionals wanted:- REXALL SHOWCASE INTERNATIONAL
Improve Your Life With

 ..To summarize, I have become very wary concerning where I buy my supplements. It isn't easy to rein in aggressive, fast-dancing companies like this.

Where to Find Resveratrol
    Today, I consulted my pharmacist friend and got the name of a company that he recommends, called "Pure Encapsulations". The best price I found so far  for 60 resveratrol capsules is $13.60, and for 120 capsules, $23.76 (plus shipping).
    I bought 60 tablets from my friend, and have started taking them.
    Another source is "Source Naturals". I found a source of these that charges $12.00 for 60 capsules, plus $4.99 shipping. 
    You are warned against taking resveratrol if you're on blood-thinning medications, or if you're regularly taking aspirin.

Will This Force a Caloric-Restricted Diet Upon You?
    If this works the way I think it will (slowing your metabolism, and lowering your core body temperature by a degree or two), then you'll be forced to go on a Weight-Watcher's diet simply in order to hold down your weight. The only break that resveratrol might give you (if my speculation is correct) is that you wouldn't have to cut you body fat to the bone. You could retain some fat and still operate at this lower metabolic (slower aging) rate. The real difference would be that resveratrol would be signaling to the cells that times were lean, and that your cells should shift into "slow mode"., rather than semi-starvation triggering this same response. What would be happening would be that your mitochondria would be processing less food and generating fewer free radicals, generating fewer cross-linkages, etc.  It would be a  bit like hibernation or aestivation. 

What's Happening With Me: A Report from Your Canary
    So what's happening with me? Have I turned green or grown a tail yet, taking all this stuff?
    First, the Huperxine-A that seemed to have made me dizzy twice before when I took it hasn't had any such effect this time after a month of daily ingestion. (In the past, when I had my "dizzy spells, Tommie was taking it too, and it didn't seem to make her dizzy. I don't know what it was but it's gone  now.) I've also been taking "Lemon Calm". Have they made a difference? I think the answer is  "yes", based upon my ability to solve tough IQ test problems, but this is totally subjective.
    I doubt that I'm eating more than 1,500 calories a day, and I'm climbing about 500 feet up the side of a mountain each day. Even so, I virtually can't lose weight. (I'm not fat, but I wouldn't mind losing three or four pounds.) I couldn't eat normally or I'd be a human balloon. 
    In August, I took my temperature a few times and was a little concerned because it was in the 95-96 (F.) range. I realized that it might signal a slower metabolism, but still, it was a bit disconcerting.
    I have plenty of energy, and I'm not particularly cold-natured.
    I feel fine, and, others than vague hints, haven't noticed any changes.
    I have an amusing story to tell you.
    One of the more reliable age markers is the length of time you can balance on one foot. To test this, you stand on a hard surface with your feet together. Then you lift one foot to about a 45-degree angle and stand there as long as you can without moving your other foot. (It didn't say anything about whether you could wave your arms and you free leg around like a windmill.)  Someone who's 20 can balance like that for 30 seconds or more. By 40, you're down to around 15 seconds. By 50, it's about 9 seconds, and by 60, it's down to 5. Beyond 70... don't ask! Anyway, standing on a hard surface, I can remain upright on one leg for 30 seconds or more, but my arms tend to move in a way that makes it dangerous to stand near me. So on Saturday, I issued this challenge to Tommie. Tommie said "You mean like this?", and proceeded to stand on one leg like a flamingo or a ballet dancer for 30 or 40 seconds. Then she said, "Or do you mean like this?", whereupon she balanced on the other leg like a statue, with the original folded up against it. 
    You can imagine what that did to my male superiority!
    I thought you'd want to know.

    One key question that concerns us us all is that of safety. I asked this of my pharmacist friend when I discussed reliable sources of resveratrol with him yesterday. He said that he was unaware of any contraindications for the three supplements at the recommended dosage levels. Of course, that doesn't mean there aren't any. One gram of acetyl-l-carnitine and 400 mg. of alpha lipoic acid per day seem intuitively a little on the high side. However, more than 50 volunteers have been taking these dosages for nearly four years. I'm sure that no one sponsoring this study wants its results marred by safety issues ,nor would they want its enrollees to be harmed. I presume that these test subjects' liver enzymes and kidney functions must have been checked during this period and found unharmed. 
    It seems to me that resveratrol is on thinner ice than ALA/ALC. The identification of resveratrol as a trigger for a reduced rate of aging is predicated upon (Dr.) David Sinclair's recent experiment with yeast (Saccharomyces cerevisiae) and Dr. Mark Tatar's experiments with fruit flies (Drosophila melanogaster?) It's the SIR2 gene that is activated in yeast to slow aging, whereas in humans, it's the SIRT1 gene that must be activated. However, resveratrol has been on the market for several years now. So far, it hasn't been recalled, so apparently, it's at least not flagrantly dangerous. The amount of resveratrol in a glass of red wine is typically of the order of 0.6 to 0.8 milligrams, whereas the amount of resveratrol in the capsules is about 5 to 10 milligrams, or about 6 to 12 times what might  be found in a glass of Upper-New-York-State Pinot Noir. However, one nagging question that attends these numbers is that of bioavailability. This has been cited in discussions re resveratrol. The resveratrol in a glass of wine may be better absorbed than the resveratrol in a pill.
    If it seems that my safety endorsements for the above supplements are less than wholehearted, it might be worth noting that I can't wholeheartedly endorse the safety of butter, eggs, milk, beef, ham, bacon, sausage, chicken, turkey, bread, potatoes and rice. I've largely abandoned them, along with dressing and gravy, pizza, burgers and fries, milkshakes... in fact, almost any processed foods. If I were physiologically 20 again, I would probably eat them with gusto, but at my age, I think it would be imprudent.

Supposing Resveratrol Doesn't Slow Aging in Humans?
    All of this assumes that resveratrol will work with humans as it does with yeast and fruit flies. There's some indirect suggestion that it does in what's termed the "French Paradox". The French eat, drink, and smoke in a way that should kill them faster than it does. The fact that they live as long and as well as they do has been attributed to the "Mediterranean diet", which includes red wine and olive oil. (Remember that flavones in olive oil can also allegedly trigger this "caloric-restricted" metabolic state.)
    Even if it doesn't keep us from growing old as fast as we would otherwise, resveratrol seems to confer many health benefits in its own right.
    Experiments on dogs and (I believe) on monkeys are scheduled to begin in a few months. 

Try This Now? Or Wait Until Later?
    My unedified guess is that Dr. Ames and his colleagues will wait until this current test with human volunteers is complete (which will probably occur when an integral number of years have passed--viz., four, five, or six. Then the results of this study will be presented in a peer-reviewed journal. Until that time, I would imagine that the principals in this experiment will want to keep the interim results of this experiment under close hold so that their publication won't be an anticlimax. However, I'm impressed that Dr. Ames feels strongly enough about this that he's willing to "fall upon his sword" for it by endorsing it so publicly in Reader's Digest. I'm sure the results he's seeing behind the scenes are good or he wouldn't be so optimistic about it.
    If I were twenty, I think I'd wait a year or two before committing to anything here. Discoveries are coming faster and faster. In the meantime, there will be more news appearing regarding both resveratrol, and the ALC/ALA combination.
    If I were thirty, it would be a judgment call. I might wait a few months or a year to see what developed, or I might try one or the other or both of the two regimens discussed above to see if they made a difference in how I felt. However, I wouldn't wait terribly long. The sooner I started, the more time I could buy in the future. (Someone starting at twenty could add another twenty years of youth and good health to her life.)



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