The Citrus flavanone naringenin prolongs the lifespan in C. elegans and slows signs of brain aging in mice
Eugenia Piragine, Martina De Felice, Lorenzo Germelli, Vanessa Brinkmann, Lorenzo Flori, Claudia Martini, Vincenzo Calderone, Natascia Ventura, Eleonora Da Pozzo, Lara Testai
Abstract
Aging is one of the main risk factors for neurodegenerative disorders, which represent a global burden on healthcare systems. Therefore, identifying new strategies to slow the progression of brain aging is a compelling challenge. In this article, we first assessed the potential anti-aging effects of the Citrus flavanone naringenin (NAR), an activator of the enzyme sirtuin-1 (SIRT1), in a 3R-compliant and short-lived aging model ( i.e. , the nematode C. elegans ). Then, we investigated the preventive effects of a 6-month treatment with NAR (100 mg/kg, orally) against brain aging and studied its mechanism of action in middle-aged mice. We demonstrated that NAR (100 μM) extends lifespan and improves healthspan in C. elegans . In the brain of middle-aged mice, NAR promotes the activity of metabolic enzymes (citrate synthase, cytochrome C oxidase) and increases the expression of the SIRT1 enzyme. Consistently, NAR up-regulates the expression of downstream antioxidant ( Foxo3, Nrf2, Ho-1 ), anti-senescence ( p16 ), and anti-inflammatory ( Il-6, Il-18 ) markers. Our findings support NAR supplementation to slow the signs of brain aging. • Aging is a main risk factor for neurodegenerative diseases. • Sirtuin 1 (SIRT1) enzyme and downstream targets are crucial in the aging process. • The Citrus flavonoid naringenin (NAR) is a SIRT1 activator. • NAR extends the lifespan and improves the healthspan in C. elegans . • Chronic supplementation with NAR slows signs of brain aging in mice.