Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence-Role of Thioredoxin-1.

The maintenance of Thioredoxin-1 (Trx-1) levels, and thus of cellular redox homeostasis, is vital for endothelial cells (ECs) to prevent senescence induction. One hallmark of EC functionality, their migratory capacity, which depends on intact mitochondria, is reduced in senescence. Caffeine improves the migratory capacity and mitochondrial functionality of ECs. However, the impact of caffeine on EC senescence has never been investigated. Moreover, a high-fat diet, which can induce EC senescence, results in approximately 1 ng/mL lipopolysaccharide (LPS) in the blood. Therefore, we investigated if low dose endotoxemia induces EC senescence and concomitantly reduces Trx-1 levels, and if caffeine prevents or even reverses senescence. We show that caffeine precludes H2O2-triggered senescence induction by maintaining endothelial NO synthase (eNOS) levels and preventing the elevation of p21. Notably, 1 ng/mL LPS also increases p21 levels and reduces eNOS and Trx-1 amounts. These effects are completely blocked by co-treatment with caffeine. This prevention of senescence induction is similarly accomplished by the permanent expression of mitochondrial p27, a downstream effector of caffeine. Most importantly, after senescence induction by LPS, a single bolus of caffeine inhibits the increase in p21. This treatment also blocks Trx-1 degradation, suggesting that the reversion of senescence is intimately associated with a normalized redox balance.

Protective Effects of Curcumin in Cardiovascular Diseases-Impact on Oxidative Stress and Mitochondria.

Cardiovascular diseases (CVDs) contribute to a large part of worldwide mortality. Similarly, two of the major risk factors for these diseases, aging and obesity, are also global problems. Aging, the gradual decline of body functions, is non-modifiable. Obesity, a modifiable risk factor for CVDs, also predisposes to type 2 diabetes mellitus (T2DM). Moreover, it affects not only the vasculature and the heart but also specific fat depots, which themselves have a major impact on the development and progression of CVDs. Common denominators of aging, obesity, and T2DM include oxidative stress, mitochondrial dysfunction, metabolic abnormalities such as altered lipid profiles and glucose metabolism, and inflammation. Several plant substances such as curcumin, the major active compound in turmeric root, have been used for a long time in traditional medicine and for the treatment of CVDs. Newer mechanistic, animal, and human studies provide evidence that curcumin has pleiotropic effects and attenuates numerous parameters which contribute to an increased risk for CVDs in aging as well as in obesity. Thus, curcumin as a nutraceutical could hold promise in the prevention of CVDs, but more standardized clinical trials are required to fully unravel its potential.