Evidence for Spermadine to Modestly Slow Aspects of Aging in Humans

Spermadine is one of many compounds identified to date that trigger some of the same beneficial stress response mechanisms that are upregulated by calorie restriction. For example, spermadine is known to boost the operation of autophagy, a collection of cellular maintenance processes responsible for recycling damaged structures and unwanted proteins. Keeping the level of damage lower means a lesser a chance of generating further detrimental consequences. The outcome, at least in short-lived species, is a longer healthy life span.

Unfortunately, the strategy of enhancing stress responses produces diminishing returns as species life span increases. The effects on longevity become ever smaller, even while the short term benefits to health tend to look quite similar. Why this is the case is not fully understood, but the data is inarguable. Humans cannot reliably live to see 150 on the basis of calorie restriction, though mice gain as much as a 40% increase to life span as a result of that intervention. Mice engineered to lose growth hormone or growth hormone receptor function live even longer yet, but the human population of Laron syndrome growth hormone receptor loss of function mutants do not appear to live significantly longer than the rest of us.

On the basis of the data noted in today's open access paper, we might tentatively add spermadine to the list of interventions that can be directly compared between humans and mice. As one might expect, these are not large effect sizes, and require continued intake over decades. Our first reaction to anything of this nature should be that we can do better than this. Indeed, we can. Instead of altering metabolism to slightly slow the pace of aging, we should be identifying the damage that causes aging and working towards therapies that can periodically repair it. That strategy has a far greater potential benefit - it can in principle achieve rejuvenation and indefinite extension of healthy life span, given sufficiently good repair technologies.

Spermidine delays aging in humans

Polyamines including spermidine play an essential role in intermediate metabolism. Since they are synthesized by higher eukaryotic cells, they are not vitamins. However, the levels of polyamines are profoundly influenced by their external supply. Our groups have shown over the past decade that supplementing spermidine by adding it to culture media (as we did for the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster) or to the drinking water (as we did for the rodent Mus musculus) is sufficient to extend longevity and to improve health span at multiple levels. Thus, in mice, the supplementation was able to suppress the age-related decline in cardiovascular function (as measured at 24 months of age) and increased overall longevity by approximately 10%.

The molecular and cellular mechanisms through which spermidine delays age-related disease and death have been elucidated to some extent. Spermidine can act as an inhibitor of EP300. EP300 acts as an inhibitor of autophagy by acetylating lysine residues within multiple proteins that are involved in autophagy-regulatory or autophagy-executing circuitries. As a result, the inhibition of EP300 by spermidine stimulates autophagy. Autophagy is required for the anti-aging effect of spermidine as indicated by the fact that genetic inhibition of autophagy abolishes the longevity-extending effects of spermidine on yeast, worms, and flies.

Until now the literature on the longevity-enhancing effects of spermidine has been limited to model organisms. Now, two prospective population-based studies report for the first time that nutritional spermidine uptake is also linked to reduced overall, cardiovascular and cancer-related mortality in humans. Both studies were based on the use of food questionnaires that allowed to calculate for each individual the nutritional uptake of polyamines including spermidine. Importantly, high spermidine uptake constituted an independent favourable prognostic parameter for reduced mortality, meaning that this variable predicted a reduced incidence of death even after correction for possible confounding factors.

In addition to the aforementioned epidemiological results, there are further, though admittedly indirect arguments in favour of a health-improving role for spermidine in human health. Thus, spermidine has been classified as a "caloric restriction mimetic" that has broad health-promoting effects due to its capacity to induce similar biochemical changes as does caloric restriction. Second, the proximal pharmacological target of spermidine is the same as that of salicylic acid, the active metabolite of aspirin (both inhibit EP300). The health-improving effects of aspirin have been initially attributed to act as an anti-coagulant. Since spermidine has not been reported to have similar anti-coagulant activity, we prefer the hypothesis that aspirin may mediate its broad pro-health effects via the inhibition of EP300.

Comments

you cant get these in supplement form. i can only find it as an experimental research chemical

Posted by: scott emptage at August 14th, 2018 4:15 PM

Just eat natto; also contains K2 and PQQ.

Posted by: CD at August 14th, 2018 8:05 PM

@CD thanks although im already supplementing with k2 and pqq, but will give this a try too.

Posted by: scott emptage at August 15th, 2018 4:42 AM

The article spotlights the fact that spermidine and aspirin both inhibit EP300. I eat a lot of spermidine rich foods, but also take a white willow bark and aspirin pill every day as a CR mimetic and now is know to inhibit EP300 as well, and may be one of the prime benefits of these 2 supplements.

Posted by: Biotechy Marcks at August 15th, 2018 8:13 AM

I used to take home made willow bark extract but it tends to cause me to wake up overheated and kind of alert at night.

Posted by: Chris Zell at August 15th, 2018 9:02 AM

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