The Effects of Hydroxytyrosol on Longevity

Executive Summary

  • A range of studies implicate activation of the Sir T proteins in longevity and the extension of life span. Resveratrol affects the Sir T proteins and it is considered to have effects on longevity.
  • An important animal study has now identified hydroxytyrosol as an important natural product which leads to greater effects on key longevity proteins compared to resveratrol.
  • Hydroxytyrosol is more effective than resveratrol in increasing levels of longevity proteins and protecting animal tissue against injury. It significantly raises the levels of multiple longevity proteins and it leads to lower levels of cell death compared to resveratrol.
  • Combined with its other demonstrated effects in published animal and human studies, including its powerful antioxidant, anti inflammatory, cardioprotective, and anti bacterial effects, hydroxytyrosol has emerged as a powerful natural product with multiple beneficial effects in animals and humans. Furthermore, hydroxytyrosol has an exceptionally strong safety profile that has been verified by the FDA.

Hydroxytyrosol Increases Levels of Key Longevity Proteins in Animals

  • Hydroxytyrosol’s superiority over resveratrol for increasing the levels of key longevity proteins has recently been demonstrated in an animal study. A recent research paper has shown that hydroxytyrosol has major effects on the expression of a series of proteins that have been implicated in longevity and increasing the life span of animal and human tissue (Mukherjee S, 2009). Importantly, this research demonstrates that hydroxytyrosol has superior effects on longevity proteins compared to resveratrol.
  • Administration of hydroxytyrosol to rats significantly increased levels of SirT 1 in cardiac tissue; of all the test compounds studied, including resveratrol, hydroxytyrosol was the most effective at increasing the levels of this pivotal longevity protein. Following the administration of hydroxytyrosol (2.5 mg/kg), the hearts of rats were examined for levels of the SirT 1 longevity protein. Of the seven SirT proteins, SirT 1 has emerged as potentially the most important with respects to increasing longevity; activation of Sirt1 promotes cell survival, and increases the life span of human muscle tissue (Motta M, 2004). Central to resveratrol’s perceived benefits on longevity is its ability to active SirT 1. The findings from this recent study demonstrate that hydroxytyrosol leads to greater levels of SirT 1 in the heart compared to resveratrol, which suggests its potentially greater effects on animal longevity.
  • Hydroxytyrosol leads to significant increases in two additional longevity proteins (SirT 3 and SirT 4) whereas resveratrol fails to significantly raise levels of SirT 3. SirT 3 and SirT 4 are localized in the mitochondria and they have been demonstrated to play important roles in the regulation of aging and energy metabolism. SirT 3 is expressed in the heart and SirT 4 is expressed in all tissues. These findings with hydroxytyrosol demonstrate its broad ranging effects on increasing the levels of three longevity proteins (SirT 1, SirT 3, and SirT 4); resveratrol failed to evoke significant increases in the levels of SirT 3 in this animal study (Mukherjee S, 2009).
  • Hydroxytyrosol’s effects on longevity proteins correlates with its stronger cardioprotective effects compared to resveratrol. Rat hearts were subject to periods of ischemia (to mimic the effects of a heart attack); the protective effects of hydroxytyrosol and resveratrol to prevent tissue injury were studied. In control hearts, the amount of dead tissue (the infarct) following the ischemic episode was approximately 40% of the total heart tissue. Hydroxytyrosol significantly halved the size of the infarct to approximately 21% (similar findings were also seen with resveratrol). However, hydroxytyrosol lead to lower levels of cell death compared to resveratrol (Mukherjee S, 2009). These findings demonstrate that hydroxytyrosol has superior protective effects on the heart compared to resveratrol. As hydroxytyrosol leads to greater levels of SirT 1 compared to resveratrol, and it increases the levels of two other longevity proteins (including SirT 4, which is expressed in all tissues), it is likely that it will exert similarly powerful protective effects in a wide range of other animal and human tissues.


Mukherjee S, et al. (2009) Expression of the longevity proteins by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and hydroxytyrosol. Free Radical Biology and Medicine, 46, 573-587.

Motta M, et al. (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell, 116, 551-563.


Dr. Matthew Killeen - CreAgri’s Scientific Affairs Advisor. Dr Killeen received his undergraduate degree in pharmacology with highest honors and was awarded a Ph.D. in cardiovascular electrophysiology from the University of Cambridge. At Cambridge he studied the mechanisms underlying sudden cardiac death and identified a number of effective pharmacological treatment strategies. Following his Ph.D., Dr. Killeen was awarded research fellowships at Harvard Medical School and the Massachusetts General Hospital. Dr. Killeen has authored 19 peer-reviewed publications in leading international journals. He is a member of the Cardiac Safety Research Consortium, a collaborative initiative between the FDA and Duke University. Dr. Killeen developed the concept for and co-chaired an FDA Think Tank on pediatric drug safety. Dr. Killeen has also previously worked for Eli Lilly and he is the author of the forthcoming book, “Cardiac Drug Safety: A Bench to Bedside Approach,” which will be published in 2011.

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