A Lecithin-Based Delivery Form of Quercetin Promotes Stress Resistance and Longevity in <i>Caenorhabditis elegans</i>.

<b>Background/Objectives</b>: 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. <b>Methods</b>: The nematode <i>Caenorhabditis elegans</i> 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(definition), 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 <i>t</i>-test, one-way or two-way ANOVA, and Bonferroni's post hoc test. <b>Results</b>: 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 <i>hsp-16.2</i> and <i>hsp-70</i>, and stimulate the <i>sod-3</i> and <i>gst-4</i> genes that are involved in antioxidant and detoxification responses. <b>Conclusions</b>: 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.