Glucosinolates and Their Bioactive Derivatives as Modulators of Age-Related Inflammation and Metabolic Decline

Healthy ageing is defined not by how long we live, but by how well. Inflammaging and declining metabolic flexibility are two interconnected drivers of late-life morbidity, together predisposing older adults to insulin resistance, sarcopenia, cardiovascular disease, and neurodegeneration. Dietary interventions that target both, with a strong safety profile and broad accessibility, are a clear priority for geroscience and public health.Glucosinolates are sulfur- and nitrogen-containing secondary metabolites found in cruciferous vegetables such as broccoli, watercress, kale, and Brussels sprouts. Myrosinase-mediated hydrolysis by plant enzymes or gut microbiota yields the bioactive derivatives responsible for their physiological effects: isothiocyanates (including sulforaphane), indoles, and nitriles. These compounds engage pathways central to ageing biology, among them NRF2-driven antioxidant responses, NF-κB and NLRP3 inflammasome suppression, AMPK/mTOR/sirtuin signalling, autophagy induction, epigenetic remodelling, and microbiota modulation. In preclinical models, the downstream effects include improved insulin sensitivity, reduced visceral adiposity, preserved mitochondrial function, lower senescent cell burden, and protection of neuronal, vascular, and musculoskeletal tissues.Key questions must be resolved before these findings can inform clinical practice. Bioavailability varies with food matrix, processing, host genotype (notably GSTM1 and GSTT1), and microbiome composition. Dose-response relationships, long-term safety in older adults, and translation of preclinical findings to human healthspan endpoints remain poorly defined. The contributions of individual derivatives versus whole-food matrices, synergies with geroprotective interventions such as caloric restriction, exercise, metformin, and rapamycin, and the need for standardised biomarkers of exposure and effect all warrant further study.This Research Topic invites original research, reviews, mini-reviews, methods papers, and clinical perspectives exploring how glucosinolates and their derivatives shape the biology of ageing and healthy longevity. We welcome submissions across the following themes:1. Mechanisms by which isothiocyanates and indoles modulate the hallmarks of ageing.2. Effects on metabolic ageing, including insulin resistance, dyslipidaemia, hepatic steatosis, adipose dysfunction, and sarcopenic obesity.3. Role of the gut microbiota in glucosinolate hydrolysis, derivative bioavailability, and downstream metabolic and immune outcomes in older adults.4. Impact on age-related disease, including cardiovascular disease, type 2 diabetes, neurodegeneration, frailty, and immunosenescence.5. Epigenetic and transcriptomic signatures of glucosinolate-derived compounds in aged tissues and biological-age clocks.6. Preclinical lifespan and healthspan studies in invertebrate, rodent, and other model systems.7. Human observational studies and clinical trials, including pharmacokinetics, dose optimisation, and biomarker development.8. Food science and nutritional approaches that preserve, enhance, or standardise bioactive content in cruciferous foods and supplements.9. Interactions and potential synergies with other geroprotective interventions, dietary patterns, or pharmacological agents.10. Safety, contraindications, and inter-individual variability shaped by genetics, sex, age, and comorbidities.Together, these contributions will build the evidence base needed to establish glucosinolate-derived compounds as accessible, food-based tools against inflammation and metabolic decline in later life, and to guide their integration into broader strategies for healthy human longevity. Topic editors: Diego A. Moreno Source: https://www.frontiersin.org/research-topics/80826/glucosinolates-and-their-bioactive-derivatives-as-modulators-of-age-related-inflammation-and-metabolic-decline