Food-Derived Bioactive Compounds in the Regulation of Cell Death and Oxidative Stress in Health and Disease

Cell death is a fundamental determinant of tissue homeostasis. Its dysregulation, driven largely by oxidative stress and pro-inflammatory signalling, underpins a wide spectrum of conditions, from skeletal muscle atrophy and neuromuscular disease to cancer and chronic organ injury. While cell death research has long been dominated by pharmacological interventions, growing evidence highlights diet as a powerful, accessible modulator of the signalling networks that govern whether a cell survives, self-renews, or is eliminated.Food-derived bioactive compounds, including polyphenols – such as flavonoids (e.g., quercetin, rutin, and epicatechin), phenolic acids (e.g., chlorogenic, gallic, and ellagic acid), and other non-flavonoid polyphenols (e.g., curcuminoids, stilbenes, and tyrosols) – as well as omega fatty acids, organosulfur compounds, bioactive peptides, and key components of the Mediterranean diet, such as extra virgin olive oil, exert pleiotropic effects on the molecular machinery orchestrating cell death. By targeting key regulatory nodes including the PI3K/Akt/mTOR, AMPK, STAT, and p53 pathways, the NF-κB-driven inflammatory cascade, and mitochondrial membrane integrity, these compounds can shift the balance between cell survival and programmed death in a tissue context, and concentration-dependent manner.The consequence of this balance is biologically dual: cytoprotective effects are highly desirable in post-mitotic tissues such as skeletal muscle, where oxidative insult drives atrophy, degeneration, and impaired regeneration; pro-death modulation, by contrast, is a therapeutic goal in transformed or dysfunctional cells, where compounds such as curcumin and plant-derived phenols have demonstrated the capacity to engage apoptotic and autophagic pathways in cancer cell lines. Understanding how the same dietary compound can promote survival in one context and cell death in another, and how oxidative stress is the pivot of this duality, is one of the most intellectually compelling questions at the intersection of nutritional science and cell biology.Despite a rapidly expanding literature, this field remains fragmented across tissue types, methodological traditions, and disease frameworks. Morpho-functional analyses (electron microscopy, confocal microscopy, immunocytochemistry), molecular and biochemical profiling, and omics approaches each offer complementary windows into the same biological process, yet are rarely integrated in a single research context. This Research Topic invites contributions that study food bioactives as modulators of cell death and oxidative stress signalling across any tissue or disease context, and that employ any combination of morphological, molecular, biochemical, or clinical approaches.Contributions addressing, but not limited to, the following themes are welcome:• Molecular mechanisms of cell death regulation by dietary bioactives: apoptosis, autophagy, necroptosis, pyroptosis, paraptosis, and their upstream regulation by food-derived compounds via PI3K/Akt/mTOR, AMPK, STAT, p53, and related signalling axes.• Oxidative stress signalling in cell fate: defining ROS-dependent cell death thresholds and leveraging dietary compounds to modulate Nrf2/HO-1, NF-κB, and MAPK pathways for mitochondrial redox homeostasis.• Food bioactives and skeletal muscle cell death: role of polyphenols, omega fatty acids, EVOO components, and Mediterranean diet patterns in attenuating oxidative stress-driven muscle atrophy, sarcopenia, and dystrophy; morpho-functional characterisation of muscle cell responses to dietary treatments.• Cytoprotection in neuromuscular and neurological disorders: dietary modulation of inflammation-driven and oxidative cell death pathways in the context of neuromuscular disease; interactions between nutritional interventions and mitophagy.• Food-derived bioactives and chronic intestinal diseases: role of food-derived bioactive components in modulating gut microbiota and improving gut barrier function, potentially to prevent chronic diseases. • Pro-apoptotic and autophagic modulation in cancer: leveraging food-derived bioactives to trigger cell death signalling cascades in tumour cell lines and in vivo models. This research focuses on the mechanistic evaluation of curcumin, plant extracts, and polyphenols against gastrointestinal (colorectal, gastric, and pancreatic), musculoskeletal (osteosarcoma and rhabdomyosarcoma), breast, and lung cancers.• Diet and chemoprevention: the role of food-derived bioactive compounds in primary and secondary chemoprevention. • Inflammation and cell death crosstalk: inflammasome regulation, caspase-1/-11 activation, and NF-κB-driven pathways as targets of dietary bioactives; pyroptosis and inflammation-associated cell death in disease models.• Morpho-functional characterisation of cell death: ultrastructural (SEM/TEM) and confocal microscopy approaches combined with biochemical and molecular assays to characterise cell death modalities modulated by food-derived compounds.• Nutrigenomic and epigenetic regulation: gene-diet interactions governing cell death gene expression; epigenetic modulation of pro-apoptotic and anti-apoptotic programmes by dietary bioactives.• Bioavailability, metabolism, and bioactivity of food compounds: gut microbial transformation and metabolite activity; structure-activity relationships for cell death modulation; dose and matrix effects.• Clinical and translational evidence: human intervention trials, epidemiological data, and clinical biomarkers linking dietary patterns or specific bioactives to markers of regulated cell death and oxidative stress burden in health and disease. Topic editors: Sara Salucci, Maria Condello, FEDERICO GIANFANTI Source: https://www.frontiersin.org/research-topics/83362/food-derived-bioactive-compounds-in-the-regulation-of-cell-death-and-oxidative-stress-in-health-and-disease