Vanillic acid improves stress resistance and substantially extends lifespan in Caenorhabditis elegans.
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abstract
Aging is the root cause of several pathologies like neurological and cardiovascular diseases. Identifying compounds that improve healthspan and extend lifespan, called geroprotectors, could be crucial to preventing or at least delaying the onset of age-related diseases. In this regard, the nematode Caenorhabditis elegans (C. elegans) is emerging as an easy, efficient, low-cost model system to screen natural products and identify novel geroprotectors. Phenolic acids can be found in a wide range of natural products that are part of the human diet. Vanillic acid is a phenolic acid that has previously been attributed with antioxidant, anti-inflammatory, and neuroprotective features. To determine whether these beneficial health effects amount to an extension of healthspan and lifespan, in this work, we thoroughly explore the effect of vanillic acid on C. elegans stress resistance and lifespan. We found that vanillic acid increases thermotolerance (19.4%), reduces protein aggregation (between 30 and 40%), improves motility, and extends lifespan by almost 50%, an extent hardly ever achieved with a natural compound. The increased thermotolerance induced by vanillic acid is independent of the insulin/IGF-1 signaling pathway but requires HSF-1 and is associated with increased HSP-4 and hsp-16.2 expression. These results provide new insight into understanding the therapeutical properties of vanillic acid and warrant further investigation of vanillic acid as a novel geroprotector.
