Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1α genes

Abstract

Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter’s redox reactions to yield hydrogen peroxide (H2O2), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H2O2, a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O2-. and H2O2. As Sirt1 and PGC-1α profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases.

Maternal exercise upregulates mitochondrial gene expression and increases enzyme activity of fetal mouse hearts

“…The concentration of H 2 O 2 affects mitochondrial biogenesis and enzyme activity. Modest induction of H 2 O 2 has been shown to promote mitochondrial biogenesis (Kamble et al 2013;Park et al 2013), while a large concentration of H 2 O 2 induces apoptosis, decreases mitochondrial enzyme activity, and leads to cardiac dysfunction (Le on et al 2007;Raisanen et al 1999). These results suggest that maternal exercise may lead to increased efficiency of mitochondria in the fetal hearts of their offspring.…”

Aspirin increases mitochondrial fatty acid oxidation

“…Mechanisms invoked to explain the benefits of salicylates include increased mitochondrial biogenesis and increased mitochondrial energy metabolism via activation of key metabolic regulators such as AMP-activated protein kinase (AMPK), NF-Kb, and SIRT1, among others [4–8]. However, these findings contradict an older literature from the 1970s and 1980s that focused on the link between aspirin and Reye Syndrome.…”

Peer Review #2 of "Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice (v0.1)"

“…Indeed, mitochondrial superoxide production was found to increase the longevity of nematodes by triggering ROS-scavenging responses [25]. It has been recently indicated that aspirin promotes mitochondrial biogenesis through H 2 O 2 production and SIRT1/PGC-1α induction in cultured mouse liver cells [26]. A most new report has also demonstrated that H 2 O 2 enables the up-regulation of mitochondria-specific SIRT3 and Mn-SOD in mice [27].…”