More proof coffee may make you old, inhibits SIRT1,2 & 3

Earlier this year I wrote this article about a compound that was isolated from coffee extract. It is called javamide-II and is a potent Sirt1 and Sirt2 inhibitor.  Various studies have determined that sirtuin activity is beneficial for health and staving of the effect of aging. Inhibition on a continuous basis might therefore accelerate aging.

The same research team has now published an additional study about another compound isolated from coffee extract. In this study they investigated the properties of javamide-I on Sirt inhibition, p53 acetylation and cell death. They also synthesized its O-methyl ester for similar analyses as the researchers main aim is to identify or develop cancer treatment compounds.

They found that javamide-I inhibited Sirt1 strongest followed by Sirt2 and Sirt3, which is different from javamide-II which is able to inhibit Sirt2 stronger than Sirt1. In silico analysis, javamide-I and its O-methyl ester both showed a competitive binding pattern for SIRT1 against NAD+. Also the kinetic data indicated that javamide-I and the O-methyl ester may be potent compounds inhibiting Sirt1 competitively.

The treatment with javamide-I and its O-methyl ester as would be expected led to increase in the p53 acetylation, suggesting that the amides could inhibit the deacetylation of p53 in the cells. Interestingly the researchers found that O-methyl ester showed an unexpected clearly higher increase in the acetylation in p53 than javamide-I with almost identical level of Sirt1/2/3 inhibition

Next the researchers verified the level of caspase 3/7 activation. The data suggest that the treatment with the O-methyl ester may increase p53 acetylation and induce caspase 3/7 activation better than javamide-I in the THP-1 cells the researchers used (THP-1 is a cell line derived from an acute monocytic leukemia patient). Cell death was clearly observed in the THP-1 cells as consequence in the case of treatment with the O-methyl ester. This data suggest that the O-methyl modification in javamide-I may be helpful in case of treatment of certain cancers.

The overall health picture for coffee consumption for non cancer affected coffee drinkers however dims with these results. Combined with the previous study it would appear that coffee drinking results in inhibition of SIRT1,2 and 3 whose activity is connected to longevity and health. Moreover it would mean that coffee counteracts the effects of NAD+ boosting with compounds like nicotinamide riboside.

The study does not specifically address bioavailability but a short paper published in April indicates that the concentration of the compounds in coffee beans might be sufficient for them to be bioactive.  Javamide-I and -II were detected in 12 coffee samples at the ranges of 0.04–2.31 mg/g. A typical cup of coffee is 30g. With 4 cups of coffee / day that would mean 5-300mg /day of SIRT1,2 and 3 inhibitors. So depending on the coffee you drink you may consume daily a dose of inhibitors.

Even though coffee contains many other active compounds and anti-oxidants that could be health promoting personally based on this I will scale back my coffee drinking. However in those unfortunate cases that you are affected by cancer it might be that coffee drinking while undergoing treatment maybe synergistic (always consult with doctors first).



4 thoughts on “More proof coffee may make you old, inhibits SIRT1,2 & 3

  • December 12, 2016 at 7:47 pm

    First, I think you’re underestimating the quantity of javamides reported in the Jae Park abstract. The title and body of the paper say pretty clearly that the amounts were determined in “coffee drinks,” not coffee beans. So when they say that “Javamide-I and -II were detected in some coffee samples at the ranges of 0.04–2.31 mg/g,” that’s 0.04–2.31 mg per gram of brewed/blended coffee, not per gram of bean. If it’s an 8 oz mug, you multiply by 236 g, not 30 g, yielding ≈9.5-546.5 mg of javamides per cup, or four times that much per 4 cups — not the 5-300 mg/day you calculate.

    Second, the sheer amount of javamides doesn’t tell you anything about potential bioactivity without bioavailability information. For all we know, they don’t make it past the intestines.

    And there is a great deal of epidemiological evidence indicating that coffee consumption is linked to lower risk of Parkinson’s disease and total mortality, so leaping from a (possible, in vitro) effect on sirtuins to “Coffee makes you old?” (even with the question mark) seems unreasonable.

    • December 24, 2016 at 9:42 pm

      Hello there, you may be right on the dosing. I recall thinking does he mean beans or ready coffee. If you are correct the amount is significantly higher. You are right that bioavailability is a factor. But when compounds are water soluble, like javamides, the chances are better they will make it at least into the bloodstream. Overall coffee is probably one of the most complex collections of bio active compounds you can consume so certainly there are also positives. Having said that humans have drunk coffee for ages and whatever coffee does we are not staying healthy.

  • January 17, 2017 at 5:49 pm

    I think I will reduce my coffee consumption as well. However the following study from 2012 shows people do live longer that drink coffee. Perhaps the benefits outweigh the SIRT inhibition. Or this effect does not occur in vivo, only in the lab.

    Freedman, N. D.; Park, Y.; Abnet, C. C.; Hollenbeck, A. R.; Sinha, R. (2012). “Association of Coffee Drinking with Total and Cause-Specific Mortality”. New England Journal of Medicine. 366 (20): 1891–1904. doi:10.1056/NEJMoa1112010. PMC 3439152Freely accessible. PMID 22591295.

    • January 18, 2017 at 12:45 pm

      Yes there are regularly studies suggesting positive effects from coffee e.g. cancer occurrence. I could imagine that coffee has more cytotoxic effects on cancer cells than on healthy cells like many plant derived polyphenols and the combination of inhibition of SIRTs is also known to increase the chances of cancer cell death. So perhaps coffee drinking should be avoided when you are young, you don’t need any anti cancer “medicine” and started at late(r) age when the risk for diseases outweighs the downsides of SIRT inhibition for healthy cells.


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