Hydroxytrosol, oxidation, inflammation and aging

Aging is not a disease but a notably strong risk factor for multiple diseases that include myocardial infarction, stroke, some ageing-associated cancers, macular degeneration, osteoarthritis, neurodegeneration and many other diseases.

For example, cardiovascular risk doubles every 10 years past the age of 40, even after adjustment for other risk factors—the rough equivalent of adding a major new risk factor (smoking, hypertension and so on) every decade (Savji, N. et al 2013). Decades of cardiovascular studies identified risk factors and showed that treating risk factors even when patients are asymptomatic prevented harm. The availability of true biomarkers of ageing, and associated clinical health outcomes and malleability to interventions (Justice, J. N. et al.; 2018), would allow geroprotectors to be tested on an accelerated time scale. They would further allow for early identification of patients at high age-related risk throughout life and in various clinical contexts to target geroprotective treatments.

Inflammation

Senescence of the immune system (known as immunosenescence) is one of the causes of ‘inflammaging’, a term coined in 2000 (Franceschi, C. et al; 2000) that refers to a phenomenon in which older organisms tend to have higher levels of inflammatory markers in their cells and tissues, which results in a low-grade, sterile and chronic pro-inflammatory status. In contrast to acute, transient inflammation—an evolutionarily conserved mechanism designed to protect the host from infections and injuries—inflammaging is linked to a myriad of age-related diseases such as cancer, type 2 diabetes, cardiovascular disease, neurodegenerative diseases and frailty (Ferrucci, L. & Fabbri, E.; 2018).

Other factors that contribute to inflammaging include genetic susceptibility, obesity, oxidative stress, changes in the permeability of the intestinal barrier associated with translocation of bacterial products (‘leaky gut’), chronic infection and defective immune cells and pro-inflammatory factors that are associated with the senescence-associated secretory phenotype of non-immune senescent cells (Rodier, F. et al. ; 2009). In addition, numerous environmental factors—such as the chemicals identified by the Tox21 consortium (Kleinstreuer, N. C. et al.; 2014)—can be cytotoxic and pro-inflammatory (Sly, P. D. et al.; 2016). Finally, longevity-enhancing interventions such as dietary restriction reduce inflammatory biomarkers (Fontana, L. ; 2009). On the basis of these findings, inflammaging is now considered to be a biomarker for accelerated ageing and one of hallmarks of ageing biology.

As discussed for other variables that influence ageing, an extended lifespan and healthspan may be a result of a fine balance between pro-inflammatory and anti-inflammatory processes (Franceschi, C. et al. ; 2007). Consistent with this idea, it has been shown that although centenarians have an increased level of pro-inflammatory molecules (for example, interleukin-6, a commonly used marker for chronic morbidity (Franceschi, C. & Campisi, J. ; 2014), the adverse consequences associated with these pro-inflammatory molecules are counterbalanced by high levels of anti-inflammatory molecules (Franceschi, C., Ostan, R. & Santoro, A.; 2018).

Hydroxytyrosol exerts an important anti-inflammatory activity.

Oxidation

In the 1950s, it was theorized that endogenous production of free radical molecules arising from oxygen and generated during fundamental metabolic processes, such as respiration, represent a key factor that drives ageing (Harman, D. ; 1956). These theories particularly focused on mitochondrial production of superoxide as a key mediator of ageing pathophysiology Harman, D.  1972). Indeed, numerous publications have shown that oxidative damage accumulates in multiple tissues and species with age. Although it is indisputable that such damage is one of the most consistent consequences of increasing age in cells and tissues.

Antioxidant (catalase, glutathione peroxidase, reductase activities, and reduced glutathione) and oxidant (oxidized glutathione, basal superoxide anion, and malondialdehyde concentrations) parameters could be proposed as markers of the rate of aging and used to ascertain biological age in humans.

Irene Martínez de Toda et al. (2020) showed that the age-related alterations of these markers are similar in humans and mice, with decreased antioxidants and increased oxidants in old participants, whereas long-lived individuals show similar values to those in adults. In addition, adult prematurely aging mice showed similar values to those in chronologically old mice and had a shorter life span than nonprematurely aging mice.

The orto-diphenolic chemical structure and low molecular weight of natural hydroxytyrosol makes it an ideal antioxidant.

In a future article we will talk about the influence of aging on our heart health.

Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed (M Tesauro et al 2017).

Genosa invests numerous human and financial resources to study the effectiveness of natural hydroxytyrosol on our health.