Caffeine extends lifespan, protects against glucose toxicity

coffee coffee

Coffee extends lifespan.

A screen for lifespan-extending drugs found six, including caffeine

A recent study set out to screen for FDA-approved drugs that might extend lifespan: FDA-Approved Drugs that Protect Mammalian Neurons from Glucose Toxicity Slow Aging Dependent on Cbp and Protect Against Proteotoxicity. (It’s a bit difficult to parse that title so that it sounds grammatically correct, but it can be done.) As we’ll see, not all of these are “drugs” in the FDA sense.

First of all, in anti-aging research, FDA-approved drugs are emphasized, since aging is not considered by the FDA to be an illness that needs treatment. If one wants to retard aging in humans, one will need to use drugs that are already available for other purposes. Rapamycin and metformin, for instance, are two of the most studied and effective anti-aging drugs, and they are used for immunosuppression and diabetes respectively. They are also both generic, so you won’t find many drug companies funding research in this area, as there’s very little money to be made.

The researchers in the above study screened many drugs. I can’t see in the paper where they have stated an exact number, but they reference a previous study that screened 88,000 compounds. The screening consisted of an assay based on neuronal cells in a medium with 15 mM (millimoles) of glucose. This amount of glucose is about three times the normal human blood glucose level, though a level easily achieved by out-of-control diabetics, and is toxic to neural tissue. The assay set out to find which drugs promoted survival in that level of glucose, and came up with 30 of them.

Then the researchers tested each of the 30 cell-survival promoting drugs on the roundworm C. elegans, the animal of choice in many anti-aging studies. (The animal is both tiny and has a short lifespan, making it ideal for this sort of thing: cheap, easily manipulated, fast results.) Six compounds were found that extended lifespan: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Since this blog focuses on actionable intelligence in medical science, we can gloss over several of those and focus on caffeine, tannic acid, and acetaminophen.

Caffeine works through a mechanism similar to dietary restriction

Caffeine extends lifespan through a mechanism that is similar to dietary restriction (DR). It inhibits mTOR, as does DR, and promotes autophagy, the cellular self-cleansing process. Many studies have noted the association between coffee consumption in humans and decreased mortality. See for example, Association of Coffee Drinking with Total and Cause-Specific Mortality, which found up to 10% lower death rates in coffee drinkers; coffee consumption is also associated with much lower rates of type 2 diabetes, and since diabetes is the pro-aging disease par excellence, this is significant for the anti-aging powers of coffee and caffeine.

Independent researchers confirmed caffeine’s lifespan-extending effects

Another recent study also found that caffeine extends life span in C. elegans: Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans. From the abstract:

The identification of caffeine as a relevant factor in aging and healthspan in worms, combined with prior work in both humans and rodents linking caffeine consumption to reduced risk of age-associated disease, suggests that caffeine may target conserved longevity pathways. Further, it may be important to consider caffeine consumption when developing clinical interventions, particularly those designed to mimic dietary restriction or modulate insulin/IGF-1-like signaling. …chronic caffeine consumption may generally enhance resistance to proteotoxic stress and may be relevant to assessing risk and developing treatments for human diseases like Alzheimer’s and Huntington’s disease….

Acetaminophen extends lifespan (!)

Another compound that extended lifespan was, surprisingly, acetaminophen (Tylenol). An interesting contrast here is that 33,000 people a year are hospitalized due to acetaminophen overdose. Anyway, I’ve no intention of taking this for lifespan extension unless and until much more is known about it. So we’ll leave that to one side.

Compounds in tea extend lifespan

The other compound worth mentioning is tannic acid, which is found in tea, berries, and oak-aged wine. However, tannic acid is not the same thing as tannins, so whether one gets a decent dose of tannic acid with one’s tea is a good question. There are many polyphenols other than tannic acid in tea, perhaps the most notable being ECGC, which increases lifespan in mammals. Tea has also been associated with increased lifespan in humans, though results are disputed and inconsistent.

Glucose toxicity: why low-carbohydrate diets are anti-aging

What’s notable about the compounds studied in this paper is that they protect against glucose toxicity. So what does that say about glucose? Obviously, in high levels it’s toxic to neurons and other tissue. This strongly suggests, in my opinion, that keeping blood sugar in the low normal range is one of the best anti-aging strategies. From the paper:

This study also suggested that the protective effects of dietary restriction and Cbp are mediated by a metabolic shift away from glucose utilization and toward beta [fat] oxidation [6]. These and other observations [7], [8] suggest that drugs which protect against glucose toxicity would plausibly mimic many of the protective effects of dietary restriction, including a reduction in age-dependent acceleration of mortality rate.

“The protective effects of dietary restriction… mediated by a metabolic shift away from glucose utilization…” Basically, it’s low-carb diets for the win. Combine low-carb with intermittent fasting – during which you drink coffee or tea of course – add some exercise and select supplements, and you’ve got perhaps your best anti-aging regimen now known.


Leave a Comment:

Joshua says January 29, 2015

“Caffeine extends lifespan through a mechanism that is similar to dietary restriction (DR). It inhibits mTOR, as does DR…”
Does this mean that caffeine is likely to inhibit strength/muscle gains, since it inhibits mTOR?

    P. D. Mangan says January 29, 2015

    It’s possible, but I suspect that the effect is going to be too small to notice.

      Joshua says January 30, 2015

      Me and thousands of other gymrats hope that this is a non-noticeable effect. Caffeine is the perfect pre-workout stimulant….I have no intention of giving it up!

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