Comments on: Interventive Gerontology 101.01: The Basics A revolution in time. Thu, 11 Apr 2013 01:11:28 +0000 hourly 1 By: Geoff Geoff Thu, 03 Nov 2011 02:57:51 +0000 This has been written here:

“To believe in the mitochondrial theory of aging as the motor of aging is akin to believing that automobiles wear out and fail because of the effects of friction. If only we could find an additive to reduce or eliminate friction, cars wouldn’t age. ”

Friction also keeps the car alive or in a functional state. Bolts, nuts and screws are used as fasteners within cars. And to keep these items fastened friction is necessary. (I won’t complicate matters here by mentioning that a nut can be welded to a bolt etc)

If a lubricant is added to the thread of a bolt and a nut, the following results: The coefficient of friction is reduced significantly. For the fastener (nut bolt combination) to maintain the same torque value, it is necessary to increase the tightening, which may damage the threads or stretch the fastener beyond its elastic limit, thereby reducing its ability to clamp.

By way of example and as you obviously know, within a car/car engine, the cylinder head conventionally is bolted to the cylinder block, the crankshaft main bearings assembly is bolted to the crankcase etc.

There was a Mechanical Engineering Professor, who I once knew, whose main focus was on friction. He use to say that the whole world is kept together by friction.

Therefore, friction in many ways is good, but yes in some cases it can be bad.

By: admin admin Mon, 31 Oct 2011 03:17:35 +0000 I don’t want to let this statement stand un-rebutted – or more accurately, uncorrected. I’m rarely as absolutist as I’m going to be here, nevertheless I will say that there is virtually no chance that mitochondrial dysfunction is THE cause of aging; and I’m surprised that, at this late date, anyone would assert such a “simple” mono-causal theory as the primary cause of aging.

To believe in the mitochondrial theory of aging as the motor of aging is akin to believing that automobiles wear out and fail because of the effects of friction. If only we could find an additive to reduce or eliminate friction, cars wouldn’t age. Friction induced wear is indeed a major cause of failure in the drive train of otherwise well maintained “working” automobiles, and arguably the majority of cars that wear out do so because of friction-related damage. However, if it were possible to eliminate friction, or to replace all the elements of the drive train as they experienced wear and failure, automobiles would still not be immortal – nor would they be spectacularly long lived. Anyone who has kept an old car running well beyond its mean lifespan will immediately understand what I’m getting at here.

The fact is, lots of things can and will go wrong, even in a comparatively simple device like a car and over relatively short periods of time. Hoses and belts will decompose and fail, the windshield and headlamp covers will become pitted and cracked, the upholstery, dashboard and other fittings will oxidize, work harden and fail, the radiator will corrode, the wiring will work harden and break… To put it simply, automobiles were not engineered to run forever. And hardly anyone would seriously suggest that any device or instrumentality would just “continue to run forever” without enormous and very costly effort and engineering. Evolution is not immune from these constraints, and in fact is arguably more driven by them than are human engineering efforts. Life didn’t arise as a perfectly working system of immortal organisms. Such immortality as exists in the biological world exists only in the form of reproduction. Reproduction is exactly the elaborately complex and cunningly engineered system we’d expect to find in any system attempting infinite survival.

Individuals are tools used by reproduction to preserve a reasonable facsimile of the genome over very long periods of time. For some organisms, such as ants, termites and many plants, the fidelity and stability of genome preservation is staggering; it is likely that some such organisms from the Permian or the Jurassic could successfully mate with their contemporary counterparts. But mostly, the pressures of the environment transmute the genome, and the organisms that carry it, in remarkable ways. If there has been effective selection pressure for the immortality of complex, multicellular individual organisms, there is no evidence of it.

Any astute observer of human (or mammalian) aging will realize at once that there is simply no engineering and no programming for us to live indefinitely. Many structures, including (importantly) the brain have no provision for indefinite maintenance. Practically from birth on, the brain experiences surprisingly steady and inexorable cell loss. If every neuronal mitochondrion could be kept at peak performance indefinitely (the equivalent of eliminating friction in an automobile), brain cells would continue to fail and die. The damage to neurons as a function of metabolism over time extends to components well beyond the mitochondria. Nuclear DNA damage would eventually prove fatal because there is essentially no nuclear DNA repair in either neurons or glial cells. There are many, many other examples of “absent maintenance” algorithms in complex multicellular organisms.

The good news is that if we look around in the natural world we can find in other organisms (and even in our own genome) many of the maintenance algorithms we’ll need if we are to become practically immortal. But what we will not find is the meta-level organization and implementation of these essential bits and pieces into a coherent, working system that will allow for the indefinite operation of dogs or cats or people. Aging isn’t some “bad mojo” that happened to a previously immortal system, anymore than an automobile wearing out is due to some deficiency in the fuel, the lubricants, or to the mechanic’s carelessness. It is possible not only to to keep an automobile running indefinitely, but to keep it in tip top condition. The British cryonicist Alan Sinclair is a master at this – in fact, he can restore devastated autos to pristine condition. However, in order to do this he has had to apply an enormous body of knowledge and clever techniques (many of which he has invented himself) which were completely outside of the manufacturer’s original design, or of their anticipation of the longevity of their product. Indeed, having watched Alan restore a number of vintage cars it easy to see that a lot of his hard labor, physical and intellectual, is due to the very fact that the manufacturers did not engineer the system for full maintenance.

Engineering biological immortality is going to be a hard, long business. It’s a common human failing that we expect that things we build (and do not understand well) will simply go on forever. This is not the case. To achieve that end requires enormous engineering and effort. — Mike Darwin

By: Abelard Lindsey Abelard Lindsey Mon, 24 Oct 2011 02:52:06 +0000 Quite the contrary, I’m nearly convinced that mitochondria is THE root cause of aging. Nick Lane, among others, has convinced me of this.

By: admin admin Mon, 29 Aug 2011 21:34:07 +0000 James, if you have cites on these studies I’d be very grateful if you could post them here. I’d be even more inclined to believe these studies if they pointed to visceral (abdominal) adiposity as a risk. For instance, in both women and men fat in the buttocks, hips and thighs does not show the correlation with CVD or Type II diabetes that visceral fat does, and in fact it may be protective. Visceral fat secretes a range of pro-inflammatory cytokines which damage everything from the vascular endothelium to the beta islet cells in the pancreas. In fact, by the time a person demonstrates an abnormal blood glucose response after a meal (postprandial blood glucose) they are estimated to have already lost 50% to 75% of their beta islet cells. Beta islet cells are non-dividing. By the the time Type II diabetes is clinically apparent, the loss of beta islet cells is estimated to be in the range 0f 75% to 85%. Loss of visceral fat, coupled with exercise, can “reverse” the clinical signs of Type II diabetes by increasing insulin sensitivity and improving the function of the remaining islet cells. However, it does not reverse the underlying loss of beta islet cells. This is one reason that I take exception to the claims of Kurzweil and others that weight loss, diet and exercise can “cure” Type II diabetes. The sad fact is that as many of these people age and experience islet cell loss from “normal” aging, they will once again become diabetic. Indeed, a sub-population of people who develop Type II diabetes do so in the 60s, 70s, 80s, and 90s, despite the absence of any major risk factors. Loss of visceral fat and increase of muscle mass can reverse symptomatic Type II diabetes. That is great, but it doesn’t equate to a cure and the loss of reserve beta islets is likely to translate into increased morbidity and mortality. — Mike Darwin

By: James Robey James Robey Sun, 28 Aug 2011 17:23:15 +0000 Just wanted to let you know that there is a study (or more) out there that seems to show that merely having low body fat confers the same longevity benefits of a caloric restriction diet.

Also, there is the Intermittent Fasting diet which is based on multiple studies showing hormonal longevity boosting benefits from fasting.

By: admin admin Sat, 13 Aug 2011 22:27:18 +0000 “I sometimes sort of fantasize that the kind of charismatic spiel used so effectively by Wallach and others could be employed for a positive purpose. But is that even possible, without crossing the line ethically, or into the realm of self delusion?”

It is, and you see it every day. It called good PR and advertising. It’s just taken for granted because its so commonplace and because it usually isn’t used to promote frankly fraudulent products. I have a personal loathing for MLM for many reasons. So, it is not easy for me to acknowledge there are MLM operations that are honest, offer reasonable value for money and adequately and fairly compensate those selling the products. Mary Kay and Avon Cosmetics are two examples. AmWay, not so much, IMHO, but they do sell products that are of quality and the sales people do profit. Every time you see an add with mutilated animals asking for money, or are visited by two fresh faced Mormons, you are looking at the same thing.

By: admin admin Sat, 13 Aug 2011 22:17:32 +0000 I think the jury is still out on telomeres in aging in humans. I’ll be discussing that in due time, so I won’t go into it here. While mitochondrial decay, and thus possibly mitochondrial biogenesis, seem a promising approach to extending lifespan, it simply isn’t credible that the mitochondria are the primary motors of aging. Aging is a multi-system failure of maintenance and regeneration from the subcellular to to the tissue and organ levels. Again, I won’t go there now, because I’m going there later in a more rigorous and detailed way.

As to Vioxx, it is probably a little better or worse than a number of the non-selective COX-I / COX-II inhibitors still on the market. The difference is that the others were old drugs that a lot of people like and need. And they are still in use today and readily available OTC. No one has done the kind of rigorous study of the CVD morality and morbidity from these OTC drugs that was done for Vioxx, because it would be problematic (they are in universal use) and incredibly costly. As to cancer Tx, there are much better angiogenesis inhibitors than Vioxx.

My point was that other NSAID drugs wreak more death and mayhem than Vioxx did every year, and yet thy are sold OTC and no one gives the truly incredibly morbidity and mortality a second thought. Any GP or ED doc will regurgitate countless stories of serious GI bleeding due to NSAIDS (and especially aspirin) on cue. Of course, they don’t mention all the hemorrhagic strokes caused by aspirin’s anti-platelet activity because they have no way to distinguish those from “regular strokes” and with so much of the population on aspirin that wouldn’t be easy.

Aspirin causes a truly gruesome and often fatal condition in children called Reye’s syndrome, and if it were any other drug than aspirin, it WOULD have been pulled from the market, Instead, a massive educational campaign was launched to teach parents not to give sick children aspirin – the rational thing to do! However, meanwhile (until the population was educated), children continued to be neurologically maimed and killed by Reye’s. I’ve dialyzed youngsters with multi-system organ failure from Reye’s and it is a wretched and heartbreaking illness with a poor outcome.

Beyond the COX-inhibiting NSAIDS, there is “Tylenol,” or more properly, acetaminophen (APAP) (paracetamol in the rest of the world). Johnson&Johnson/MacNeil are apparently getting tired of paying for liver transplants and paying out judgments for people who die of liver failure because this hepatotoxic drug has spread into almost every product on the market for pain or discomfort, ranging from nostrums for menstrual cramps to sleep aids. APAP toxicity is the most common cause of hepatic failure requiring liver transplantation in Great Britain. In the United States, APAP toxicity has replaced viral hepatitis as the most common cause of acute liver failure, and it is the second most common cause of liver failure requiring transplantation in the US.The percentage of cases of acute liver failure caused by an overdose of acetaminophen increased considerably from 1998 to 2003, with unintentional overdose accounting for at least half of these case. Acetaminophen (APAP) is now the drug of choice for suicide in the US & UK and the number of deaths and hospitalizations from APAP has risen steadily since its widespread introduction in the 1960s (it was initially introduced inthe1950s). I can’t find the numbers for the US, but in England and Whales there are ~700 successful suicides/yr using APAP. The drug interacts unpredictably with alcohol in many individuals to cause serious liver toxicity and the economic costs of APAP toxicity are estimated to be in the hundred of millions of dollars/yr. I note that few,if any other PRESCRIPTION, let alone OTC drug, with a decades long history of steadily escalating injury and death to the population. By contrast, Vioxx was a dream drug! So it is the hypocrisy and unfairness of the treatment of Vioxx that I find objectionable.

Having said that, Vioxx was over-prescribed and Merk knew it had a problem long before they acted. Due to biochemical variations in individuals, a given NSAID, like other drugs, may provide great relief to a sub-population of patients, whilst doing nothing, or being no better than existing drugs, for others. It’s use should have been confined to those who really demonstrated substantial benefit, for whom other drugs were ineffective and who were informed of, and accepted the risk. The same is likely true of many other drugs that fare logged relentlessly to a wide populations of patients, such as Crestor and Zyprexa. There are no demon drugs, there are just misused drugs, and some are much easier to misuse than others. Unfortunately, the Pharms have little economic choice but to try to maximize sales for each and every approved drug. At a cost of near a billion per drug approved, it is simply not economical to restrict the use of any approved drug to the population that will benefit most. To recover the enormous capital cost of introducing a new drug it is necessary to sell every milligram of the molecule possible, whether it is the best drug for a given patient, or not.. — Mike Darwin

By: Abelard Lindsey Abelard Lindsey Sat, 13 Aug 2011 06:16:31 +0000 I have no interest in TA-65 because I don’t think telomere shortening is a cause of aging. The differential turn over rates of different cell types in the body make clear that telomere maintenance is a regulated process. Whatever the real cause of aging (I’m convinced its mitochondrial dysfunction), it damages telomere maintenance just as it damages everything else. This is why I think TA-65 is unlikely to work as a life extension agent. Mitochondrial biogenesis is necessary for life extension.

Vioxx inhibits vascular growth, which is why it is associated with heart attacks and strokes. Since cancer cells rely on greater vascularization than regular cells, this suggests that Vioxx was used for the wrong purpose. It seems to me the Vioxx would be useful as part of a regiment to treat cancer.

By: Shannon Vyff Shannon Vyff Sat, 13 Aug 2011 05:49:25 +0000 I remember the colloidal mineral craze Luke ;) I’ve often wished for a charismatic leader in Cryonics–but alas, charismatic leaders often achieve their charm by offering “facts that will extend your life” -some actual ones, but many that are easily falsified. The problem with human life-span is that it takes so many years to prove anything touted as anti-aging or rejuvenating as right or wrong. With Cryonics, we don’t even have a fully functioning mammal that has been preserved for any significant length of time–just evidence of what looks like functional neurons, and other things that show it might work some day. Couple the lack of hard proof with the problems inherent throughout time with human interactions within society and you get what looks like a very poor bet. One that few are willing to take.

Calorie Restriction isn’t even “proven” conclusively, yet more evidence points to it working and there are only a few thousand world wide who actively follow it, hardly more than are signed up for Cryonics.

By: Luke Parrish Luke Parrish Sat, 13 Aug 2011 05:08:55 +0000 Delusion is incredibly prevalent, and easy to fall into. It seems the older I get the more I realize this. (Granted, it is probably not age so much as education that drives this home.) But plenty of things go beyond mere self-delusion and into a realm where deliberate deception of others is (almost!) certainly the aim. Take the claims of Dr. Joel Wallach, which were some of the first life extension claims I ever heard as a kid. They were passed around in audio tape form as part of an MLM scheme, and lots of people (myself included, it shames me to say) took them for gospel. Here’s a good debunking of the claims from an actual nutritionist:

I sometimes sort of fantasize that the kind of charismatic spiel used so effectively by Wallach and others could be employed for a positive purpose. But is that even possible, without crossing the line ethically, or into the realm of self delusion?