The process of aging population is increasing the relevance of comprehending age-related changes in skin structure and function, as well as their implications for clinical care. This narrative review explores aspects of the intrinsic and extrinsic mechanisms of skin aging, their molecular and morphological consequences, and their clinical expression, with particular attention to chronic cutaneous insufficiency. The intrinsic aging process is reflecting declining cellular functionality, impaired tissue homeostasis, and endocrine changes, especially regarding estrogen deficiency after menopause. These processes are reducing collagen synthesis, hydration, and elasticity and thus contributing to epidermal and dermal atrophy and barrier dysfunction. On the other hand, extrinsic aging is driven mainly by cumulative ultraviolet exposure, with additional contributions from pollution, smoking, diet, and behavioral and psychosocial factors. Processes such as oxidative stress, inflammation, DNA damage, glycation, and increased matrix metalloproteinase activity promote extracellular matrix degradation, linking the environmental exposure to the photoaging and cutaneous carcinogenesis. Main clinical manifestations include xerosis, chronic pruritus, pigmentary changes, benign lesions, actinic keratoses, and basal cell and squamous cell carcinomas. Inflammatory, allergic, autoimmune, and drug-induced dermatoses, including psoriasis, lichen planus, and bullous pemphigoid, are complicating healthcare in older adults, while systemic comorbidities and medication use are influencing clinical presentation and treatment. Dermatoporosis is characterized by cutaneous atrophy, purpura, pseudoscars, and susceptibility to injury after minor trauma. Reduced hyaluronic acid availability and CD44 expression contribute to impaired hydration and mechanical resilience, potentially leading to ulceration and deep dissecting hematomas. Management measures are emphasizing the role of photoprotection, skin hydration, trauma prevention, and reduction of modifiable exposures, with corticosteroid use warranting reassessment in secondary dermatoporosis. Other discussed approaches are topical hyaluronic acid, retinoids, alpha-hydroxy acids, and vitamin C, but the proposed interventions have limited supporting evidence. Therefore, it is considered that early recognition of these interconnected changes may be supportive for planning prevention, a timely diagnosis, and individualized care, based on considerations like skin fragility, associated disease, and treatment burden in older patients.
Multi-target phytotherapeutic and nutraceutical interventions have been proposed as complementary strategies in metabolic dysfunction-associated steatotic liver disease (MASLD), yet the interpretation of treatment-associated changes in interleukin-11 (IL-11) remains uncertain. Historically associated with tissue protection and regeneration, IL-11 has sometimes been regarded as a potentially favorable biomarker; however, recent evidence challenges this interpretation. This Perspective critically reappraises the biological role of IL-11 in metabolic liver disease. A narrative critical appraisal was integrated with evidence-informed mapping of a representative twelve-component phytotherapeutic formula onto processes implicated in hepatic IL-11 induction. Current evidence links hepatic IL-11 signaling through the interleukin-11 receptor alpha (IL-11Rα)/gp130 complex to lipotoxic and oxidative stress, hepatocyte injury, hepatic stellate-cell activation, and fibrogenesis, while cross-sectional human data associate circulating IL-11 with fibrosis severity in MASLD. Four competing, not necessarily mutually exclusive, hypotheses are proposed: upstream suppression (H1), adaptive rise (H2), extrahepatic/off-axis effects (H3), and null/analytical variability (H4), generating testable predictions regarding IL-11 trajectories and biomarker relationships. A treatment-associated increase in circulating IL-11 should therefore not be interpreted a priori as a favorable regenerative response without independent evidence of reduced hepatic injury or fibrogenic activity. A staged validation strategy is proposed to prospectively distinguish among these interpretations.
Oxidative stress plays a major part in the development of chronic and degenerative diseases such as cancer, arthritis, aging, autoimmune disorders, cardiovascular and neurodegenerative diseases. Cardiovascular disease is the leading cause of death in the United States and Europe and is poised to become the most significant health problem worldwide. Reactive nitrogen species are involved in the regulation of cardiovascular motor tone, modulation of myocardial contractility, control of cell proliferation and inhibition of platelet activation, aggregation, and adhesion. Cellular constituents of our body are altered in oxidative stress conditions, resulting in various disease states. The oxidative stress can be effectively neutralized by enhancing cellular defenses in the form of antioxidants. To understand the mechanism of action of antioxidants, it is necessary to understand the generation of free radicals and their damaging reactions.
A significant number of neurological diseases are pathogenetically related to oxidative stress, including but not limited to cerebrovascular afflictions such as ischemic and hemorrhagic stroke, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and so on. Natural nutrients may help limit the impact of oxidative stress and, therefore, delay or prevent the impairment of these diseases. Although these natural components have not entered routine use, many have been studied in preclinical or even clinical settings with promising results. Therefore, the need to find the stage of the research in the field of validating the properties and clinical usefulness of such nutrients represents the main reason this narrative review was conducted. This analysis explored the PubMed database for papers related to the influence of natural nutrients on the onset and evolution of some of the most severe neurological disorders. The results of the review provide an overview of the pathways oxidative stress may undertake and how the use of nutrients may counteract these pathways. In conclusion, natural nutrients may have beneficial effects that can be impactful on clinical outcomes, but more good quality research in this field is needed before formulating any clear recommendation.
