Introduction: Aging is a normal, inevitable, irreversible, and progressive process which is driven by internal and external factors. Oxidative stress, that is the imbalance between prooxidant and antioxidant molecules favoring the first, plays a key role in the pathophysiology of aging and comprises one of the molecular mechanisms underlying age-related diseases. However, the oxidative stress theory of aging has not been successfully proven in all animal models studying lifespan, meaning that altering oxidative stress/antioxidant defense systems did not always lead to a prolonged lifespan, as expected. On the other hand, animal models of age-related pathological phenotypes showed a well-correlated relationship with the levels of prooxidant molecules. Therefore, it seems that oxidative stress plays a more complicated role than the one once believed and this role might be affected by the environment of each organism. Environmental factors such as UV radiation, air pollution, and an unbalanced diet, have also been implicated in the pathophysiology of aging and seem to initiate this process more rapidly and even at younger ages. Aim: The purpose of this review is to elucidate the role of oxidative stress in the physiology of aging and the effect of certain environmental factors in initiating and sustaining this process. Understanding the pathophysiology of aging will contribute to the development of strategies to postpone this phenomenon. In addition, recent studies investigating ways to alter the antioxidant defense mechanisms in order to prevent aging will be presented. Conclusions: Careful exposure to harmful environmental factors and the use of antioxidant supplements could potentially affect the biological processes driving aging and slow down the development of age-related diseases. Maybe a prolonged lifespan could not be achieved by this strategy alone, but a longer healthspan could also be a favorable target.

Carbon monoxide (CO) has always been recognised as a toxic gas, due to its higher affinity for haemoglobin than oxygen. However, biological studies have revealed an intriguing role for CO as an endogenous signalling molecule, a gasotransmitter. CO is demonstrated to exert many cellular activities including anti‐inflammatory, antiapoptotic, and antiproliferative activities. In animal studies, CO gas administration can prevent tissues from hypoxia or ischemic‐reperfusion injury. As a result, there are a plethora of reports dealing with the biological applications of CO and CO‐releasing molecules (CORMs) in inflammatory and vascular diseases. CORMs have already been tested as a therapeutic agent in clinical trials. More recently, an increased interest has been drawn to CO’s potential use as an anticancer agent. In this review, we will aim to give an overview of the research focused on the role of CO and CORMs in different types of cancer and expand to the recent development of the next generation CORMs for clinical application in cancer treatment.

Characterized by a complex pathophysiology that includes the intraneuronal formation of neurofibrillary tangles and the extracellular deposition of β-amyloid plaques, Alzheimer’s disease (AD) is a terminal neurodegenerative disease that causes dementia in older adults. Oxidative stress in the brain is considered as one of the contributing factors to the pathogenesis of AD, and thus, antioxidants have attracted much interest as potential therapeutic agents against the disorder. Natural antioxidants are typically characterized by low acute and chronic toxicity, which facilitates their potential therapeutic application. One important molecular target for the beneficial effects of natural antioxidants is the nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2). NRF2 is a key transcription factor that orchestrates the cellular antioxidant response through regulating the expression of oxidative stress-related genes harboring the antioxidant response element (ARE) in their promoters. Indeed, in the case of excessive oxidative damage, NRF2 migrates to the nucleus and binds to ARE, activating the transcription of antioxidant protector genes. There is increasing evidence that NRF2 is implicated in AD pathology through dysfunction and altered localization, which renders it as a potential therapeutic target for AD. Thus, this review summarizes the most recent (2018-2023) advances on the NRF2-modulating activity of natural antioxidants observed in vitro and in AD animal models. This information will help elucidate the molecular mechanisms governing the antioxidant activity of such phytochemicals to highlight their therapeutic potential against common neurodegenerative diseases, such as AD.

Cancer is a group of diseases with significant morbidity and mortality. In cancer cells, where energy requirements are exceptionally high, angiogenesis, which is the sprouting of new blood vessels from pre-existing ones, is an important process for tumour survival and progression. Hence, extensive research in recent years focuses on the discovery of new anticancer drugs that target angiogenesis. Several methodologies have been developed preclinically, including the inhibition of pro-angiogenic factors and their receptors via micromolecular agents or monoclonal antibodies and the inhibition of other compensatory pathways beyond the traditional angiogenic ones. The purpose of the literature review is to present new anticancer drugs that target the process of angiogenesis and have been under preclinical or clinical investigation during the last five years. Many new anticancer drugs targeting angiogenesis are identified in the literature. The results of the in vitro and in vivo evaluation of these drugs show that, apart from inhibiting angiogenesis, they also affect cancer cell proliferation and tumour growth. Recent clinical studies show that these drugs increase the overall or disease-free survival of patients, even those with persistent, chemotherapy-resistant and metastatic types of cancer, although treatment-related side effects are not uncommon. Drugs that target the process of angiogenesis are likely to be the future of anticancer therapy, especially in cases where more traditional treatments do not produce the desired results and where combination regimens of anti-angiogenic agents with standard chemotherapeutics increase patient survival.