Progressing Wisdom Requires Lifespan Extension

Leonard Hayflick, one of the world’s preeminent experts on aging, was a founder of the Council of the National Institute on Aging… He discovered the Hayflick limit: human cells reproduce only so many times (around 64 times). After a while, their telomeres, the end of their chromosomes, shorten too much  (others found that and got a Nobel for it). As telomeres shorten, the cell divide/reproduce less and less. Incapable of freshening themselves up through division, those cells become senescent: those decaying cells live much longer than healthy cells, while dysfunctioning, causing inflammation…[1]

One would think that a top aging researcher would be all for life extension. But just the opposite! Hayflick and his associates have vehemently condemned “anti-aging medicine” and criticized organizations such as the American Academy of Anti-Aging Medicine, about the desirability of life expansion [2]. Hayflick believes that, as he and associates put it in an anti anti-aging manifesto in 2002:

“To slow, or even arrest, the aging process in humans is fraught with serious problems in the relationships of humans to each other and to all of our institutions.”

That is of course true. But that doesn’t mean it’s a bad thing, just the opposite. Hayflick, like most people from the elite profiting from the establishment, implicitly assumes the context that our “institutions” are the best, and that so are “relationships of humans with each other”. However, tribalism, racism, sexism, and ageism, among other characteristics of “relations of humans with each other” are rampant nowadays, if not outright massive (just ask LGBT people or Christians in Pakistan, or the losing middle class in the West, reduced to vote to trump or his ilk…)

Moreover, the biosphere is in the greatest crisis since the dinosaurs, thanks to “our institutions”. So the evidence is that “our institutions” may have to be annihilated, before they annihilate us.

But Hayflick turns into a Nazi-like fundamentalist, and, that’s the beauty of his extremist psychology, without realizing it. He rages on: “By allowing antisocial people—tyrants, dictators, mass murderers, and people who cause wars—to have their longevity increased should be undesirable…I would rather experience the aging process as it occurs, and death when it occurs, in order to avoid allowing the people who I just described to live longer.”

Kill them all! We don’t want a few bad apples to live any longer, so let’s kill all the apples! All those who are familiar with the logic of the Inquisition are familiar with that exact reasoning: kill them all, so a few miscreants can die.

This was the famous: “Massacrez-les tous, car le Seigneur connait les siens!” (Massacre them all, as the Lord knows his own) uttered by Arnaud Amaury, légat pontifical (representant of the Pope) et abbot of Cîteaux, according to the Cistercian Césaire de Heisterbach. During the siege of Beziers (20,000 killed the Pope was officially told). That was during the crusade against the Cathars. Cathars were annihilated, from south France to Constantinople, killing five millions, more than the populations of the British Isles at the time.

Anyway, Hayflick exhibits exactly same mentality, absolute righteous infamy, throwing the baby with the bath, in the name of the Good Lord… And he doesn’t suspect that at all. Like all the infamous ones, and Hitler was a famous case, he poses as the giver of moral lessons… fighting infamy (which Hitler identified with the Jews).

I prefer Brigitte Bardot young in body. I would also prefer to be her, young in body. But I prefer BB older in mind: she has become much wiser, embraced the seals…. BB In j-L Godard Le Mepris 

In other words, Hayflick would rather kill them all, than seeing a handful of people live longer. This is, ironically enough, exactly the argument that the people he hates so much, tend to use. Infamous individuals (say Hitler, Stalin, Mao) were depicted to their subjects as loving and so incredibly concerned, that justice as fairness and happiness in a much better society, was only a few miscreants away… who had just to be put out of order.

It’s interesting to ponder why Hayflick would embrace the same psychological strategy of the mass murdering power hungry psychopaths he professes to condemn? Simple: The force of hatred is strong in human beings. Simply uttering grotesquely offensive hateful talk against humanity is very satisfying. Hatred evolved as deep psychobiology to cull people. Its addictive character goes a long way to explain systematic mass subjugation & murdering!

Besides, here is a little selfish angle, progress on fighting aging would be too late coming for Hayflick personally. Thus, just to make sure after embracing the fundamental principle of the mass murderers (I kill them all, because some have displeased me, as La Fontaine pointed out:”Si ce n’est toi, c’est donc ton frere!), Hayflick embraces aging itself as a superior value. One may as well embrace what one can’t escape: animals being devoured are full of endorphins. As aging devours Hayflick, Hayflick pontificates that aging is a good thing.

Aging is a horrible thing, the ultimate disease. Recently an Australian scientist, 104 years old, decided he would travel to Switzerland… to commit euthanasia. His argument? He is bored. It’s true that, as mindful people age, and their bodies betray them, with hearing, sight, locomotion shutting down, they are less motivated to live.

So is there hope for anti-ageists? Well, no before some spending. It’s the same problem as with power producing thermonuclear fusion: not enough spending, that is, not enough activity.

There is only one optimal way to be a human being: young and strong, Being ravaged by disease doesn’t improve us as humans, just the opposite. Better being a bimbo (BB is NOT a brainless bimbo) than proffering Nazi moods, as Hayflick did… Under the pretext that, because he did some excellent lab manipulations, he is expert at wisdom too…

Hayflick himself pointed out that only 3% of the National Institute of Aging budget is spent on research on aging. More than 50% of the money (hence activity) is spent on Alzheimer’s disease. In contempt, Hayflick proposed to call that Institute, the Alzheimer Institute. Alzheimer doesn’t have much to do with aging (they are somewhat correlated; many older people don’t get it… but middle age people can get it…)

So why should a massive effort be made on aging? First young people, flush with hormones, including rage, and colossal naivety, are the ones going to war (or the ones who can be persuaded to go to war). Look at the Nazis: a few leaders were in their forties, most of them were much younger. They knew nothing, if they had known enough, they would have realized Nazism made no sense, and would prove self-destructive…

Second, and related to the first point, we need more aging to gather more wisdom. Wisdom is proportional to the significant knowledge one has gathered, and that’s proportional to lifespan. This is perhaps why some whales live so long, several centuries: one needs a long time to become an expert mammal living in the sea, capable of teaching others.

Hayflick also claimed anti-aging couldn’t work. The theory of that is absurd; individual whales have been found with extremely old harpoon heads in their flesh. So mammals can be made to live centuries. In an extremely fast evolving species such as the genus Homo, the species with the shortest lifespans would evolve the fastest, and that would have to be balanced with decades of lifespan to gather enough wisdom to make for a wise enough species. Now we need much more wisdom, to evolve in other ways, so lifespan extension is an evolutionary advantage.

And can it be done? Well the first anti-aging medication that works is around [3]. At least, it works on rodents, and has been known to work on hearts (indirectly). It’s viewed suspiciously because some suspect it may rejuvenate some cancers too. Nobody has said the world was simple. Actually greater wisdom is a greater ability to manage a more complicated world.

Extremes are teachers.

Patrice Ayme

***

***

[1] Senescent cells cause inflammation, are dysfunctional and gets in the way of still functioning cells. Could eliminating them bring some measure of rejuvenation? It does. Experiences on mice show this unambiguously. It extends the better functioning lifespan. Drugs may be developed to do so in humans

https://www.nia.nih.gov/news/drug-combo-removes-senescent-cells-restores-cell-growth-obese-mouse-model

Senescent cells destroying drugs even bring on neurogenesis, as senescent cells are cleared. It is known that, even in very old people neurogenesis is needed for a fully functioning mind.

Ogrodnik, M. et al., Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis, Cell Metabolism, Published online January 3, 2019. https://doi.org/10.1016/j.cmet.2018.12.008.

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[2] Hayflick is 91.

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[3] Nicotinamide Adenine Dinucleotide (NAD), is a key factor in the cellular production of energy. Often brandished as NAD+, the name of its oxidized (brownish) form, the molecule participates in a host of metabolic pathways and is involved in other important processes, such as DNA repair. NAD+levels naturally decline as people and animals age, and this loss has been proposed as contributing to the underlying physiology of aging.

Studies show that boosting NAD+ levels can extend life span in yeastworms and mice. Animal research also promises that NAD+’s improves several aspects of health (that was known for decades for human heart). Raising levels of the molecule in old mice appears to rejuvenate mitochondria—the cell’s energy factories, which falter as we age (making us sick, inflamed, weak and stupid). Other mouse studies have demonstrated benefits such as improved cardiovascular functionenhanced muscle regeneration and better glucose metabolism with NAD+ supplementation.

As Hayflick is himself close to death, he can observe that at least two anti-aging techniques work, in mice… And for deep and excellent reasons having to do with the nature of cellular machinery…

As the philosopher said, to be human is to be hopeful. Hayflick’s gloom and doom fits well to his general appeal to all mass murderers, starting with aging itself, to rise to the occasion…

 

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8 Responses to “Progressing Wisdom Requires Lifespan Extension”

  1. ronaldscheckelhoff Says:

    “So why should a massive effort be made on aging? First young people, flush with hormones, including rage, and colossal naivety, are the ones going to war (or the ones who can be persuaded to go to war)”

    This reminds me of a recent study done with wolves. They looked at many different packs of wolves (they number 7-10 wolves per pack, so amount to family units). It was discovered that the packs with the oldest elders (or having at least one elder) – had a much higher rate of success against rival packs who lacked the Canis Lupus seniors. Just like humans, the wolves equivalent of a tribe or clan is prone to war with rival clans. Wolves are often compared to humans for a number of reasons, and their structure of living is similar in some ways.

    The reason the success rate was higher? The elder wolves are “consulted” – including by the alpha wolf – for decisions about whether or not to engage. The elder wolves vote a lopsided situation down every time.

    I seriously liked my own canis lupus familiaris. He passed recently, and was an elder. They’re smarter than given credit for.

    Like

    • Patrice Ayme Says:

      Wow. Didn’t hear of that one, very interesting, thanks. That would reflect the importance of wisdom. Well known in elephants with matriarchs… If those get shot remaining elephants go stupid…

      Like

  2. Gmax Says:

    Can NAD be used in younger people to slow down aging?

    Like

  3. beni Says:

    Great graphics! Let’s have more like that!

    Also, investigate C60, a buckyball of carbon that is an antioxidant >400X stronger than vitamin C, that quells inflammation and apparently lengthens telomeres, improves vision, and increases physical strength. Comes in a suspension in olive oil or other veg oil.

    Basically, the problem with your argument, from a purely epistemological point of view, is that the “crystallized intelligence” of elders may work in an environment that has disappeared since their youth, and only youth still flexible enough to be pushed into randomized trial and error will find the new optimum.

    Just sayin’, you’re totally ageist.

    Like

    • benign Says:

      cheers,
      benign

      Like

    • Patrice Ayme Says:

      Somehow your comment went into moderation, unbeknownst to me. I am of course not ageist. “Still flexible” is the key. Human elders as they are presently are all too often “crystallized” as you put it. I am talking about ETERNAL YOUTH.

      Like

    • Patrice Ayme Says:

      C60, really????
      I can’t see how that would work… Not exactly a natural element abundantly found… Whereas NAD+ is natural:

      Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
      Christopher R. Martens, Blair A. Denman, Melissa R. Mazzo, Michael L. Armstrong, Nichole Reisdorph, Matthew B. McQueen, Michel Chonchol & Douglas R. Seals
      Nature Communications 9, Article number: 1286 (2018) | Download Citation

      Abstract
      Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.

      Introduction
      Advancing age is the primary risk factor for the development of cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in industrial and post-industrial societies1. The increase in CVD risk with aging is driven largely by adverse changes to arteries, including stiffening of the aorta, and by increases in systolic blood pressure2. As such, interventions designed to lower blood pressure and/or improve arterial function hold promise for preventing age-related CVD.

      Chronic calorie restriction (CR) prevents the development of arterial dysfunction and increases in blood pressure with aging in rodents3,4, and lowers arterial stiffness and blood pressure in overweight-obese middle-aged and older adults5,6. Despite numerous health benefits, adherence to chronic CR remains poor and possibly even unsafe in normal weight older adults7,8,9. As such, there is a critical need to establish safe, practical alternatives to regular CR for enhancing cardiovascular function and health with aging in humans10.

      The recent identification of several key molecular mechanisms responsible for CR-mediated longevity in model organisms has led to an exciting search for “CR-mimetic” interventions to improve cardiovascular and other physiological functions with aging11,12. In this regard, nicotinamide adenine dinucleotide (NAD+) has emerged as a critical signaling molecule and essential substrate for sirtuins, a class of enzymes that mediate several of the beneficial effects of CR in model organisms13,14, including the maintenance of cardiovascular function15. Moreover, CR has been shown to increase NAD+ levels in pre-clinical models16,17. The cellular bioavailability of NAD+ and related metabolites declines in animals and in humans during normal aging13,18,19,20,21 and may contribute to physiological aging by reducing sirtuin activity. Although NAD+ can be synthesized de novo from the amino acid tryptophan, this process does not occur in all tissues, requiring most cells to rely on a salvage pathway for regenerating NAD+ from other intracellular intermediates, which are primarily made available through dietary sources22. Vitamin B3 (niacin: i.e., nicotinic acid and nicotinamide) enters this salvage pathway and acts as a NAD+ precursor; however, nicotinic acid is associated with undesirable flushing at therapeutic doses23 and nicotinamide does not reliably activate (and may even inhibit) sirtuins despite raising concentrations of NAD+24,25,26. Therefore, administration of nicotinic acid or nicotinamide is unlikely to be widely adopted for maintaining health and function with aging.

      In contrast to these compounds, oral supplementation with either of the NAD+ metabolites, nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), increases levels of NAD+ and improves multiple physiological functions in animal models18,27,28. Indeed, we recently demonstrated that supplementation of NMN in the drinking water improved cardiovascular function in old mice29. Moreover, CR increases concentrations of NR and NAD+ and restores normal circadian gene transcription in the liver, further suggesting that NR may act as a CR mimetic30. Thus, NMN and NR are NAD+ boosting compounds that hold promise for enhancing cardiovascular health and physiological function with aging31,32.

      Despite these encouraging results from preclinical studies, the tolerability and effectiveness of chronic supplementation with NMN or NR have not been established in humans. Because NR is readily taken up by cells and acts as a direct vitamin precursor for NAD+ synthesis33, its recent development as a dietary ingredient (NIAGEN®, ChromaDex Inc., Irvine, CA) has provided the first opportunity to translate the potential benefits of NAD+ boosting molecules to people. In this regard, a recent study showed that single doses of NR stimulated blood cellular NAD+ metabolism in healthy humans in a dose-dependent manner26. However, the tolerability of chronic NR supplementation and its efficacy for increasing NAD+ bioavailability have not been established in humans, and we lack even initial insight into the potential of NR for improving cardiovascular and other physiological functions with human aging.

      To address these important research gaps, we conducted a small randomized, placebo-controlled, crossover clinical trial of NR supplementation (500 mg, 2×/day) to assess its overall tolerability and efficacy vs. placebo for raising levels of NAD+-related metabolites in healthy middle-aged and older men and women. We also took the opportunity to gain preliminary insight into the effects of chronic NR supplementation for improving cardiovascular and other physiological functions associated with risk of clinical diseases and/or disability with aging. Our results demonstrate that 6 weeks of NR supplementation at this dose is well-tolerated in humans and effectively increases blood cellular NAD+ concentrations. Exploratory analyses of the effects of chronic NR supplementation on physiological function in this cohort of healthy middle-aged and older adults suggest that the potential for reducing systolic blood pressure and arterial stiffness may be the most promising hypotheses to investigate in future larger-scale clinical trials, particularly in individuals with elevated baseline blood pressure.

      Like

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