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Background: Growing evidence indicates an association between ambient air pollution and decreased human reproductive potential. This study aims to systematically review the association between air pollutants and female ovarian reserve., Methods: The literature was searched in six electronic databases through June 2024. Screening the 136 articles retrieved for inclusion criteria resulted in the selection of 15 human observational studies that evaluated the effect of environmental pollutants on ovarian reserve markers. The study protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration code: CRD42023474218)., Results: The study design of the selected studies was found to be cross-sectional (2 of 15), retrospective cohort (10 of 15), prospective cohort (2 of 15), and case-control (1 of 15). The study population was distributed as follows: Asians (53%, eight studies), Americans (33%, five studies), and Europeans (14%, two studies). The main findings showed a higher body of evidence for the environmental pollutants PM2.5, PM10, and NO 2 , while a low body of evidence for PM1, O 3 , SO 2 , and a very low body of evidence for benzene, formaldehyde, and benzo(a)pyrene, yet consistently showing significant inverse association data. The overall methodological quality of the selected studies was rated moderated across the 14 domains of the National Institutes of Health (NIH) toolkit., Conclusion: The data suggest that increased exposure to air pollutants seems to be associated with reduced ovarian reserve, with the most substantial evidence for pollutants such as PM2.5, PM10, and NO 2 . However, more evidence is needed to draw conclusions about causality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zupo, Castellana, Nawrot, Lampignano, Bortone, Murgia, Campobasso, Gruszecka Kosowska, Giannico and Sardone.)

Introduction: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aβ clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aβ monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results., Areas Covered: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU)., Expert Opinion: Solanezumab was one of the first anti-Aβ monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aβ level by acting on soluble monomeric form of Aβ peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aβ cascade hypothesis of AD.

The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.