The global population is on a trajectory of continuous growth, with estimates projecting an increase from 7.7 billion in 2019 to approximately 9.7 billion by 2050. Longevity is also expected to rise rapidly, with advancements in healthcare contributing to increased life expectancies and an increase in the maximum lifespan. The aging process is accompanied by different changes, often leading to a decline in daily life activities and an increased susceptibility to disease. Age-related changes can cause cellular damage and subsequent cellular death. Oxidative stress and inflammation play significant roles in this process contributing to molecular damage and mitochondrial dysfunction. Active aging has been associated with improved quality of life and a reduced risk of morbidity and premature mortality. In this context, the Mediterranean diet has emerged as a promising approach to promoting healthy aging and sustainability. The phytochemical compounds within the Mediterranean diet have been linked to a lower risk of developing cardiovascular disease, type 2 diabetes, obesity, cancer and neurodegenerative diseases. The findings of peer-reviewed articles regarding the use of the Mediterranean diet as a healthy and sustainable dietary pattern written in Portuguese, Spanish or English were included in this narrative literature review. This dietary pattern\'s emphasis on the consumption of fresh and local food aligns with both health and environmental sustainability goals. This work provides a comprehensive review of the benefits of the Mediterranean diet and its components in a healthy aging process and highlights the importance of this dietary pattern as a sustainable approach.

UNASSIGNED: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint.
UNASSIGNED: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells.
UNASSIGNED: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner.
UNASSIGNED: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.

Quercetin is a polyphenol present in numerous fruits and vegetables and therefore widely consumed by humans with average daily dietary intakes of 10-20 mg/day. It is also a popular dietary supplement of 250-1000 mg/day. However, despite the widespread consumer interest in quercetin, due to its possible chemopreventive properties, the extensively studied quercetin presents a highly diverse and complex array of biological effects. Consequently, the present paper provides the first assessment of quercetin-induced hormetic concentration/dose responses, their quantitative features and mechanistic foundations, and their biological, biomedical, clinical, and public health implications. The findings indicate that quercetin-induced hormetic dose responses are widespread, being independent of biological model, cell type, and endpoint. These findings have the potential to enlighten future experimental studies with quercetin especially with respect to study design parameters and may also affect the appraisal of possible public health benefits and risks associated with highly diverse consumer consumption practices.

An analysis of China\'s domestic publications revealed that China\'s hormesis-related research was enormously underestimated. China\'s documented hormesis-related research spans at least four decades, covers a broad spectrum of research areas, and is more abundant than previously thought. These findings should be considered in historical assessments of the concept of hormesis. Moreover, similar to the international literature, different terms have been used to describe the same phenomenon (hormesis), which hampers communication, generalization of findings and accumulation of knowledge. Hence, we advocate that \'hormesis\' should be cited as a keyword in all the relevant publications written in Chinese language.

3-Bromopyruvate (3-BP) is a glycolytic inhibitor and a potential calorie restriction mimic that shows a variety of beneficial effects in several aging model systems. A chronic low dose of 3-BP was given to male Wistar rats for 4 weeks. The effect of 3-BP on age-dependent alteration on the activities of various transporters/exchangers and redox biomarkers (protein carbonyl [PC], sialic acid [SA], sulfhydryl group [-SH], intracellular calcium ion [Ca2+]i, and osmotic fragility) was studied. In aged rats, 3-BP treatment increases the membrane-bound activities of Na+/K+-ATPase (NKA) and Ca2+-ATPase (PMCA), along with levels of -SH and SA. It also exerts a concomitant decrease in Na+/H+ exchanger (NHE) activity and the levels of [Ca2+]i, PC, and osmotic fragility in aged groups. 3-BP can be considered as a potential antiaging agent that induces a hormetic effect leading to amelioration of age-dependent impairment of membrane-bound ATPases and alterations in the redox biomarker level.

Evidence of contaminant-induced hormesis is rapidly accumulating, while the underlying mechanisms of hormesis are becoming increasingly understood. Recent developments in this research area, and especially the emergence of the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) as the master mechanism, suggest that contaminants can induce cardiac hormetic responses. This paper collates significant evidence of hormetic response of the heart rate of fish embryos to contaminants, in particular antibiotics, microplastics, and herbicides, characterized by a low-dose increase (tachycardia) and a high-dose decrease (bradycardia). The increase often occurs at doses about 100-800 times smaller than the no-observed-adverse-effect-level (NOAEL). There are also indications for even triphasic responses, which include a sub-hormetic decrease of the heart rate by doses over 106 times smaller than the NOAEL. Such sub-NOAEL effects cannot be captured by linear-no-threshold (LNT) and threshold models, raising concerns about environmental health and highlighting the pressing need to consider hormetic responses in the ecological risk assessment. A visionary way forward is proposed, but addressing this research bottleneck would require improved research designs with enhanced ability and statistical power to study diphasic and triphasic responses of heart rate.

This paper demonstrates that ginseng mixtures and individual ginseng chemical constituents commonly induce hormetic dose responses in numerous biological models for endpoints of biomedical and clinical relevance, typically providing a mechanistic framework. The principal focus of ginseng hormesis-related research has been directed toward enhancing neuroprotection against conditions such as Alzheimer\'s and Parkinson\'s Diseases, stroke damage, as well as enhancing spinal cord and peripheral neuronal damage repair and reducing pain. Ginseng was also shown to reduce symptoms of diabetes, prevent cardiovascular system damage, protect the kidney from toxicities due to immune suppressant drugs, and prevent corneal damage, amongst other examples. These findings complement similar hormetic-based chemoprotective reports for other widely used dietary-type supplements such as curcumin, ginkgo biloba, and green tea. These findings, which provide further support for the generality of the hormetic dose response in the biomedical literature, have potentially important public health and clinical implications.

Numerous agents (approximately 90) are shown to stimulate hair growth in cellular and animal models in a hormetic-like biphasic dose response manner. These hormetic dose responses occur within the framework of direct stimulatory responses as well as in preconditioning experimental protocols. These findings have important implications for experimental and clinical investigations with respect to study design strategies, dose selection and dose spacing along with sample size and statistical power issues. These findings further reflect the general occurrence of hormetic dose responses within the biological and biomedical literature that consistently appear to be independent of biological model, level of biological organization (i.e., cell, organ, and organism), endpoint, inducing agent, potency of the inducing agent, and mechanism.

Curcumin is shown to commonly induce biphasic dose responses in a broad range of cell types, with particular emphasis on neural cells, including neuronal stem cells. The quantitative features of these biphasic dose responses, with respect to the magnitude and width of the low dose stimulation, are similar to those reported for hormetic dose responses. These hormetic dose responses occur within the framework of direct stimulatory responses as well as in preconditioning experimental protocols, displaying acquired resistance within an adaptive homeodynamic framework. These findings have important implications for study design strategies involving dose selection and spacing, as well as sample size and statistical power considerations. These findings further reflect the broadly general occurrence of hormetic dose responses that consistently appear to be independent of biological model, endpoint, inducing agent and mechanism.

This commentary briefly summarizes the extraordinary resurgence of hormesis within the biological, biomedical, toxicological and risk assessment domains over the past two decades. It places this resurgence within the context of challenging the scientific validity of the threshold and linear dose responses. It argues that conducting research on mechanisms that actuate and regulate the stimulatory response features of hormesis will provide the knowledge needed to develop potentially transformational applications aimed at protecting and enhancing biological resiliency as well as treating/curing a multitude of diverse medical conditions.