Abstract
It is believed that curcumin, a component of the turmeric that belongs to hormetins, possesses anti-aging propensity. This property of curcumin can be partially explained by its influence on the level of sirtuins. Previously, we have shown that relatively high (2.5-10 μM) doses of curcumin induce senescence of cancer cells and cells building the vasculature. In the present study we examined whether curcumin at low doses (0.1 and 1 μM) is able to delay cell senescence and upregulate the level of sirtuins in human cells building the vasculature, namely vascular smooth muscle (VSMC) and endothelial (EC) cells. To this end we used cells senescing in a replicative and premature manner. We showed that low doses of curcumin in case of VSMC neither postponed the replicative senescence nor protected from premature senescence induced by doxorubicin. Moreover, curcumin slightly accelerated replicative senescence of EC. Despite some fluctuations, a clear increasing tendency in the level of sirtuins was observed in curcumin-treated young, senescing or already senescent cells. Sirtuin activation could be caused by the activation of AMPK resulting from superoxide elevation and ATP reduction. Our results show that curcumin at low doses can increase the level of sirtuins without delaying senescence of VSMC.
Highlights
Curcumin, a natural compound derived from Curcuma longa, is considered as a potent anti-aging factor [1, 2]
To analyze the impact of curcumin on replicative senescence in vitro, cells were cultured in medium supplemented with curcumin at concentrations that do not limit cell proliferation
Curcumin can act cytotoxically, cytostatically - pro-senescent activity (2.5-7.5 μM) [24], and it is believed that low doses have a beneficial effect for the organism, in accordance with the hormetical activity of this www.impactjournals.com/oncotarget compound
Summary
A natural compound derived from Curcuma longa, is considered as a potent anti-aging factor [1, 2]. NAD-dependent deacetylases, are involved in DNA repair, genome stability, telomere structure maintenance and in epigenetic modifications of histones [9] Their activity is considered as potentially anti-aging, activators of sirtuins could be regarded as potential anti-aging compounds. It is believed that sirtuins are responsible for lifespan elongation of model organisms and are the key elements elevated during caloric restriction [10, 11]. They are necessary for the proper functioning of the cardiovascular system [12, 13, 14]. There are suggestions that curcumin acts by sirtuin activation [6, www.impactjournals.com/oncotarget
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