Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances stress resistance and delays aging in vivo. Methods: The nematode Caenorhabditis elegans was used as an animal model to evaluate the effects of QF under physiological and stress conditions. Unformulated Q was administered as a control. Worm survival, healthspan, resistance to thermal and oxidative stress, and expression of stress- and longevity-related genes were assessed. All the experiments were conducted at least in triplicate, each including a minimum of 15 worms. The data were analyzed using Student’s t-test, one-way or two-way ANOVA, and Bonferroni’s post hoc test. Results: One hundred micromolar Q administered in QF was more effective than equimolar unformulated Q in increasing the worms’ ability to resist acute thermal stress at 35 °C (tested on 75 worms/group) and oxidative stress caused by 0.5 mM hydrogen peroxide (tested on 75 worms/group). In this last case, the protective effect of QF was similar to that of N-acetylcysteine and ascorbic acid. Under experimental conditions mimicking the long-term consequences of thermal stress, QF, like Q, increased the worms’ lifespan and healthspan by approximately 50%, counteracting the age-related decline associated with stress (120 worms/group). These benefits are supported by QF’s capacity to act as a reactive oxygen species scavenger; suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate the sod-3 and gst-4 genes that are involved in antioxidant and detoxification responses. Conclusions: These findings suggest that Q, when administered in the QF formulation, can act at the transcriptional level to protect against aging induced by stressful conditions.
Romeo et al. (Tue,) studied this question.