Crataegus Species as a Source of Geroprotective Phytochemicals: Biological Activities, Molecular Mechanisms and Therapeutic Perspectives.

Population aging has intensified the search for natural compounds capable of promoting healthy aging and preventing age-related diseases. Among medicinal plants, species of the genus Crataegus (hawthorn) have attracted increasing attention because of their rich phytochemical composition and broad spectrum of biological activities. This review summarizes and critically evaluates current evidence on the geroprotective potential of Crataegus species, integrating data from phytochemical, pharmacological, and mechanistic studies. Particular attention is given to the major bioactive constituents of Crataegus, including flavonoids, oligomeric proanthocyanidins, phenolic acids, and triterpenoids, which exhibit antioxidant, anti-inflammatory, cardioprotective, neuroprotective, metabolic, and anticancer properties. We discuss the growing evidence that these phytochemicals target multiple hallmarks of aging by modulating oxidative stress, chronic low-grade inflammation (inflammaging), mitochondrial dysfunction, cellular senescence, and the senescence-associated secretory phenotype (SASP). Their biological effects are mediated through key signaling pathways involved in cellular homeostasis and longevity, including Nrf2/ARE, NF-κB, PI3K/Akt/mTOR, AMPK, and SIRT1. The review also critically examines findings from in vitro, in vivo, and available clinical studies, highlighting both the therapeutic potential and current limitations of Crataegus-based interventions for age-related disorders. Although preclinical evidence strongly supports the multi-target geroprotective properties of Crataegus species, clinical validation remains limited. Overall, Crataegus represents a promising source of natural geroprotective agents with the potential to promote healthy aging through the modulation of multiple aging-related molecular pathways. Future well-designed clinical studies are essential to establish their efficacy, safety, optimal dosage, and long-term therapeutic value in humans.