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Thursday 10 December 2015

Ageing and anti-oxidants: in search for a new paradigm

Gerard Friedlander (Paris Discartes University Medical School)

Since 1956, the oxidative stress theory of Dr. Harman involves oxidative stress as one of the main cause of aging and age-related diseases. But today, a growing number of evidences are challenging this theory and the causative role of reactive oxygen species (ROS) in aging or age related diseases is questioned. Indeed, published data do not support a determinant role in longevity of ROS, neither a superior antioxidant defenses.

For example, many long-living species such as naked mole rat, bat or birds exhibit high levels of oxidative damage even at young ages challenging this theory.

Studies have shown that naked mole rat, an exceptionally long-living rodent (>30 years), exhibit higher level of oxidative damages in all biomolecules (lipids, proteins and DNA) as well as lower antioxidant capacity suggesting a higher susceptibility to oxidative damages (Andziak et al., 2004; 2005; 2006; Kasaikina et al., 2011). It is highly unlikely that antioxidants are responsible for the longevity of these animals.

Similarly, studies on other long-living animals such as bats, showed discrepancies in levels of ROS production with higher production in brain mitochondria and lower production in heart as compared to short live bats (Brunet-Rossinni et al., 2004). Another study showed no significant differences in hydrogen peroxide production (which reflect ROS production) between 12 short and long-lived species (Lambert et al., 2007).

In addition, several recent studies have shown that low levels of oxidative stress could be beneficial and promote longevity in c.elegans (Yang et al., 2010, Van Raamsdonk et al., 2012). More specifically, they found that ROS effect were compartment specific – elevated ROS in the mitochondria increased lifespan, while elevated ROS in the cytoplasm decreased lifespan (Schaar et al., 2015).

Collectively these mixed findings do not support the oxidative stress theory.

In addition, many supplementation of traditional antioxidant as “anti-aging” therapy haven’t been demonstrated to be beneficial in any of the study performed (De Grey 2000; Linnane et al., 2007; Sanz et al., 2006). On the contrary, several recent studies have demonstrated a deleterious effect of antioxidant supplementation in tumor initiation, progression and metastasis (Harris et al., 2015, Sayin et al., 2014, De Nicola et al., 2011). With the most recent study showing a deleterious effect of antioxidant in skin melanoma metastasis (Piskounova et al., 2015)

In this context, a growing number of studies covering numerous fields are challenging the antioxidant dogma. Considering the importance of antioxidant in cosmetics, it appears critical to translate these results and these new mechanisms to this field. 

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