Structural Determinants Research Articles

Association of Area Deprivation Index With Mortality in Critically Ill Adults With COVID-19.

Various social determinants of health have been established as significant risk factors for COVID-19 transmission, prevalence, incidence, and mortality. Area deprivation index (ADI, a composite score made up of educational, housing, and poverty markers) is an accepted multidimensional social determinants of health measure. Little is known about how structural social determinants of health before hospitalization, including ADI, may affect mortality related to COVID-19 in critically ill patients. To examine the association of ADI with intensive care unit (ICU) mortality in patients with COVID-19 and compare its predictive power with that of clinical factors. This was a retrospective cohort study of critically ill adults with COVID-19 in 3 hospitals within a single health system. Multivariable logistic regression models (adjusted for demographic and clinical variables) were used to examine the association of ADI with ICU mortality. Data from 1784 patients hospitalized from 2020 to 2022 were analyzed. In multivariable models, no association was found between national ADI and ICU mortality. Notable factors associated with ICU mortality included treatment year, age, van Walraven weighted score, invasive mechanical ventilation, and body mass index. In this study, clinical factors were more predictive of mortality than ADI and other social determinants of health. The influence of ADI may be most relevant before hospital admission. These findings could serve as a foundation for shaping targeted public health strategies and hospital interventions, enhancing care delivery, and potentially contributing to better outcomes in future pandemics.

Building decolonial nursing curricula to address disparities in Indigenous women's maternal health

Social and health inequities and inequalities are rising all over the world (Smith, 2012; McGibbon et al., 2014; Chinn and Falk‐Rafael, 2018). Nursing students should therefore be educated to understand the multifaceted factors creating health inequities and the degree to which non-biological elements can be embodied and become biological (e.g., environmental stress leading changes in health.). The need for innovative undergraduate nursing curricula reform is apparent. The lack of nursing courses highlighting the effects of colonization, environmental justice, upstream structural and social determinants of health, globalization, and state violence must be addressed. Colonization, broadly speaking, characterizes the Eurocentric project to “civilize” the rest of the world utilizing various forms of violence (McGibbon et al., 2014). The persistent and ongoing reproduction and recurrence of colonialism, enacting cycles of disenfranchisement and oppression, creates significant inequities in physical, mental, and emotional health and well-being for historically marginalized groups of people (Smith, 2012). Because gaps in nursing curricula and outdated teaching practices may support persistent inequities, scholars and students have advocated for decolonization of nursing curricula (Smith, 2012; McGibbon et al., 2014; Chinn and Falk‐Rafael, 2018). This analysis utilizes decolonial theory and postcolonial feminism to suggest pathways to decolonize nursing curricula and pedagogy through decentering the colonial knowledge structures and practices that harm Indigenous health and wellbeing.

Addressing Social and Structural Determinants of Health in the Delivery of Reproductive Health Care: ACOG Committee Statement No. 11.

Social and structural determinants of health include historical, social, political, and economic forces, many of which are rooted in racism and inequality, that shape the relationship between environmental conditions and individual health. Unmet social needs can increase the risk of many conditions treated by obstetrician-gynecologists (ob-gyns), including, but not limited to, preterm birth, unintended pregnancy, infertility, cervical cancer, breast cancer, and maternal mortality. An individual health care professional's biases (whether overt or unconscious) affect delivery of care and may exacerbate and reinforce health disparities through inequitable treatment. Obstetrician-gynecologists and other health care professionals should seek to understand patients' health care decision making not simply as patients' individual-level behavior, but rather as the result of intersecting sociopolitical conditions, structural inequities, and social needs that create and maintain inequalities in health and health care. Recognizing the importance of social and structural determinants of health can help ob-gyns and other health care professionals to better understand patients, effectively communicate about health-related conditions and behavior, and contribute to improved health outcomes, including patients' experience of care and their trust in the health care system.

Asking Why Is Necessary to Address Health Disparities: A Critical Approach for Solution-Oriented Environmental Epidemiological Research.

In environmental epidemiology, we use an array of tools from various, related disciplines to answer key questions about environmental exposures in relation to health outcomes. Typically, we ask questions related to what, who, where, when, and how. We value these questions because they contribute to novel scientific discovery and our understanding of disease etiology linked to environmental exposures. In addition, these questions help us better understand who might be at highest risk of exposure and subsequent risk of disease. Although necessary for the goals of environmental epidemiology, these questions are insufficient for addressing environmental health disparities. Specifically, these questions may be able to help us describe exposure-health outcome associations but are limited in their ability to move beyond identification to intervening on observed disparities to achieve environmental health equity. We sought to emphasize the need to value and routinely add the key question of "Why?" in environmental epidemiological studies. In asking this additional critical question, we can identify and incorporate the structural determinants and drivers of environmental exposure disparities and determine whether these factors are linked to existing and historically recalcitrant health disparities. Further, we can design effective studies that build on existing frameworks to address the fundamental causes of environmental health disparities. This commentary underscores the need to routinely incorporate "why" questions in the practice of environmental epidemiology. By asking and addressing "Why?" we can employ better, more solution-oriented study designs, improve data collection, and enhance our ability to collaborate with diverse study populations through trust-building and community-engaged research. Incorporating these approaches will move environmental epidemiology forward from mostly documenting to actively addressing environmental health disparities. https://doi.org/10.1289/EHP14513.

Flexible Fluorine-Thiol Displacement Stapled Peptides with Enhanced Membrane Penetration for the Estrogen Receptor/Coactivator Interaction.

Understanding how natural and engineered peptides enter cells would facilitate the elucidation of biochemical mechanisms underlying cell biology and is pivotal for developing effective intracellular targeting strategies. In this study, we demonstrate that our peptide stapling technique, fluorine-thiol displacement reaction (FTDR), can produce flexibly constrained peptides with significantly improved cellular uptake, particularly into the nucleus. This platform confers enhanced flexibility, which is further amplified by the inclusion of a D amino acid, while maintaining environment-dependent α helicity, resulting in highly permeable peptides without the need for additional cell-penetrating motifs. Targeting the ERα-coactivator interaction prevalent in estrogen receptor-positive (ER+) breast cancers, we showcased that FTDR-stapled peptides, notably SRC2-LD, achieved superior internalization, including cytoplasmic and enriched nuclear uptake, compared to peptides stapled by ring-closing metathesis (RCM). These FTDR-stapled peptides utilize different mechanisms of cellular uptake, including energy-dependent transport such as actin-mediated endocytosis and macropinocytosis. As a result, FTDR peptides exhibit enhanced anti-proliferative effects despite their slightly decreased target affinity. Our findings challenge existing perceptions of cell permeability, emphasizing the possibly incomplete understanding of the structural determinants vital for cellular uptake of peptide-like macromolecules. Notably, while α helicity and lipophilicity are positive indicators, they alone are insufficient to determine high cell permeability, as evidenced by our less helical, more flexible, and less lipophilic FTDR-stapled peptides.

Structural determinants of M2R involved in inhibition by Sigma-1R

Structural determinants of M2R involved in inhibition by Sigma-1R

Novel structural determinants and bacterial death-related regulatory effects of the scorpion defensin BmKDfsin4 against gram-positive bacteria

Numerous defensins constitute a family of cationic antimicrobial peptides with high degrees of sequence variability, and in-depth characterization of their structural basis and antibacterial mechanisms remains limited. Here, a representative scorpion defensin, BmKDfsin4, with two distinct hydrophobic and basic residue clusters, was extensively investigated. The hydrophobic residue cluster, formed by Phe2, Pro5, Phe6, Phe28 and Leu29 residues, strongly influences the antibacterial activity of BmKDfsin4 against Gram-positive bacteria. Compared with the three scattered Lys13, Lys30 and Arg32 residues, the basic residue cluster, consisting of the Arg19, Arg20, Arg21 and Arg37 residues, played a less important role. The synergistic interaction between the basic residue cluster and Arg32 significantly affected BmKDfsin4 function. The bacterial growth inhibition by BmKDfsin4 was associated with regulating expression levels of cell division-related genes, cell wall synthesis-related genes and bacterial autolysis-related genes rather than destroying the bacterial cell membrane. The coincubation of BmKDfsin4 with the bacterial strains induced gradual changes in the bacterial surface from a rough and thin surface to a noticeably wrinkled surface together with abundant white spots and even complete cavities within the bacteria. These findings revealed novel structural determinants and bacterial death-related regulatory effects of the defensin BmKDfsin4 and highlighted diverse antibacterial mechanisms of defensins.

Targeting c-Met in Cancer Therapy: Unravelling Structure-Activity Relationships and Docking Insights for Enhanced Anticancer Drug Design.

The c-Met receptor, a pivotal player in oncogenesis and tumor progression, has become a compelling target for anticancer drug development. This review explores the intricate landscape of Structure-Activity Relationship [SAR] studies and molecular binding analyses performed on c-Met inhibitors. Through a comprehensive examination of various chemical scaffolds and modifications, SAR investigations have elucidated critical molecular features essential for the potent inhibition of c-Met activity. Additionally, molecular docking studies have provided invaluable insights into how c-Met inhibitors interact with their target receptor, facilitating the rational design of novel compounds with enhanced efficacy and selectivity. This review highlights key findings from recent SAR and docking studies, particularly focusing on the structural determinants that govern inhibition potency and selectivity. Furthermore, the integration of computational methodologies with experimental approaches has accelerated the discovery and optimization of c-Met inhibitors, fostering the advancement of promising candidates for clinical applications. Overall, this review underscores the pivotal role of SAR and molecular docking studies in advancing our understanding of c-Met inhibition and guiding the rational design of next-generation anticancer agents targeting this pathway.

Intersectionality shapes the access to various adaptive resources in climate-vulnerable contexts

Abstract Intersectional approaches are becoming essential to understanding the differential impacts of climate change and the heterogeneity of adaptive capacities. Varying factors of social and economic privileges and inequalities synergistically shape the local power structure, ultimately determining disproportionality and unequal access to adaptive resources. Using empirical data from coastal Bangladesh, which is part of the Ganges Delta, and one of the world’s -most climate-vulnerable regions, this study shows how religion, gender, and ethnicity intersect with patterns in (i) farm and non-farm incomes, (ii) land conflicts, (iii) the size of farms, and (iv) access to critical sources of weather information. The study highlights that multilayered identity, which is shaped by various structural determinants, including local power structure, can determine gendered dimensions of access to various adaptation resources. It also shows that if policymakers and development partners partially understand or do not understand the complex landscape of local vulnerability or unequal power structures including the adaptive capacity of the vulnerable populations, they would not be able to provide critical support in times of crisis. The concept of intersectionality is therefore critical in addressing adaptation and risk management challenges for regions like the Ganges Delta and other parts of the world, where people are struggling with similar social and environmental challenges.

Habitat dimensionality and feeding strategies but not temperature as determinants of body size-trophic structure relationship in a marine food web.

Disentangling the determinants of trophic structure is central to ecology. The capacity to capture subjugate and consume a prey (i.e. gape limitation) is a relevant limitation to acquire energy for most organisms, especially those in smaller size ranges. This generates a size hierarchy of trophic positions in which large organisms consume small ones. Body size is tightly correlated to gape limitation and explains a large fraction of variance in the body size-trophic position relationship. However, a considerable fraction of variance still remains to be explained. Consumer search space dimensionality (2D or 3D) and feeding strategies, temperature and the size structure of primary producers can alter the trophic structure, but tests based on information from natural food webs are scarce. We generated specific predictions about the body size trophic position relationship and evaluated them using information from a subtropical South Atlantic coastal marine ecosystem: benthic realm (2D, rocky shore and sandy beach) and the pelagic realm (3D). We characterized this marine coastal food web based on stable isotopes of carbon and nitrogen from 256 samples from primary producers (macroalgae and phytoplankton) to large predators (sand shark) in summer and winter. Consumer body size encompassed six orders of magnitude in weight from 10-2 to 6 × 104 g. Isotopic signal corresponded to an integration of carbon sources from basal consumers to top predators. The body size-trophic position relationship showed a linear positive association with different slopes for the benthic and pelagic environments. This implies a smaller predator prey size ratio for pelagic (3D) with respect to benthic consumers (2D) as theoretically expected. No seasonal differences were found in slopes and most of the overall variance in benthic environments was largely explained by feeding strategies of the different taxonomic groups. We provide an integrated evaluation on the role of body size, consumer search space and feeding strategy to understand the determinants of trophic position. Results demonstrate that integrating gape limitation hypothesis, the dimensionality of consumer search space and feeding strategies into a formal robust framework to understand trophic structure is feasible even in complex natural ecosystems.

Crystal Structure and Mutagenesis of an XYP Subfamily Cyclodipeptide Synthase Reveal Key Determinants of Enzyme Activity and Substrate Specificity.

Cyclodipeptide synthases (CDPSs) catalyze the synthesis of diverse cyclodipeptides (CDPs) by utilizing two aminoacyl-tRNA (aa-tRNA) substrates in a sequential ping-pong reaction mechanism. Numerous CDPSs have been characterized to provide precursors for diketopiperazines (DKPs) with diverse structural characteristics and biological activities. BcmA, belonging to the XYP subfamily, is a cyclo(l-Ile-l-Leu)-synthesizing CDPS involved in the biosynthesis of the antibiotic bicyclomycin. The structural basis and determinants influencing BcmA enzyme activity and substrate selectivity are not well understood. Here, we report the crystal structure of SsBcmA from Streptomyces sapporonensis. Through structural comparison and systematic site-directed mutagenesis, we highlight the significance of key residues located in the aminoacyl-binding pocket for enzyme activity and substrate specificity. In particular, the nonconserved residues D161 and K165 in pocket P2 are essential for the activity of SsBcmA without significant alteration of the substrate specificity, while the conserved residues F158 as well as F210 and S211 in P2 are responsible for determining substrate selectivity. These findings facilitate the understanding of how CDPSs selectively accept hydrophobic substrates and provide additional clues for the engineering of these enzymes for synthetic biology applications.

Structural determinants of customer loyalty among long-term insurance consumers in Namibia

Structural determinants of customer loyalty among long-term insurance consumers in Namibia

Are migrant workers at greater risk of workplace deaths? A systematic review and meta-analysis

Abstract Background Globally, 170 million individuals migrate for work. Yet, evidence on their mortality risk remains unclear. Our aim was to synthesize global evidence on migrant worker mortality risk compared to local workers and to identify the multiple intersecting social determinants of mortality. Methods We conducted a systematic review of peer-reviewed literature which reported on mortality outcome of migrant workers. Studies published between 1 Jan 2000 to 17 Jan 2023 in English were searched in MEDLINE, Embase, PsycINFO, and Ovid Global Health. Meta-analysis using random effects model was used to calculate pooled estimates and narrative synthesis was used to develop a data-driven framework on intersectional social determinants. Results Out of 11,495 identified records, 44 were included, of which 11 were pooled in meta-analyses. The combined migrant worker death count was 44,338, with data from 16 countries, including migrants from agriculture, construction, and service industries. Compared to local workers, migrant workers had a higher risk of fatal occupational injury (pooled RR = 1.71, 95%CI: 1.22-2.38, I² = 99.4%), and a lower risk of all-cause mortality (pooled RR = 0.94, 95%CI: 0.88-0.99, I² = 90.7%). Key social determinants associated with increased mortality risk were either migration-related (e.g. lower language proficiency, undocumented status) or labour-related (e.g. precarious employment, labour migration policies) interacting over migrant workers’ life course. Conclusions As the largest evidence synthesis to date, these findings indicate that migrant workers have higher fatal occupational injury rates than local workers, indicating the need for tailored protections for migrant workers. These data confirm that the all-cause mortality advantage observed in migrant populations applies to the working population. Future interventions should be designed to address both migration- and labour-related determinants of migrant worker health. Key messages • Migrant workers have a higher risk of workplace fatality despite being generally healthier than local workers, explained by structural determinants such as precarious employment. • Future interventions must address migration- and labour-related social determinants of health at structural levels, such as extending labour protection laws to migrant workers.

Impact of organisational injustice on health and wellbeing of female police: A meta-ethnography

Abstract Background Female police officers face more bias, discriminatory treatment, and insufficient support compared to male officers, resulting in poorer health outcomes. This meta-ethnographic review investigates beyond individual responsibilities to explore the dimensions of policing, and their effects on the health and well-being of female police officers. Methods The study reviewed qualitative and mixed-method studies (2000-2022) on the health and well-being of female police officers. Ten databases were searched using keywords related to health, well-being, women, police, and qualitative study. Twenty-one papers were synthesised, analysed, and interpreted using a seven-phase inductive and interpretative meta-ethnographic approach. Results The data analysis unveiled a distinct outcome, indicating a strong correlation and significant impact of organisational injustice on the health and well-being of women in law enforcement. Our research findings imply that organisational injustice, including procedural, relational, distributive, and gendered injustice, notably affects the health and well-being of female officers, with mental health being frequently cited, followed by effects on social, workplace, and physical health. Furthermore, the consequences of these four types of organisational injustice, alongside related cultural, systemic, and structural risk factors, reach beyond the immediate health and well-being of individual female officers. They also hinder various aspects of their professional lives, such as career advancement and maintaining a healthy work-life balance, potentially exacerbating long-term health and well-being issues. Conclusions This review emphasizes addressing organisational injustice and related cultural, systemic, and structural determinants in policing for healthier work environments for female officers. Policy makers must scrutinize gender-neutral policies affecting women, enabling transformative action for safer, supportive, and healthier workplaces. Key messages • Organisational injustice in various forms, significantly impact health and wellbeing of female police officers, necessitating policy reforms. • Addressing organisational injustice embedded in seemingly gender-neutral policies and practices, is vital for ensuring equitable treatment and health promotion of female police officers.

Inequalities in preterm birth by deprivation and ethnicity: A national cohort study in England

Abstract Background Preterm birth has decreased in the UK; however, the extent of inequalities remains unclear. This study aimed to quantify socioeconomic and ethnic inequalities in preterm birth rates using routinely collected maternity data in England. Methods Retrospective analysis of cohort data from the NHS England Hospital Episode Statistics (HES). All women aged 13-55 with a singleton livebirth (April 2018 to March 2021) at 24-42 weeks were included. Multivariate Poisson regression was used to estimate the rate of preterm birth (livebirth between 24 + 0 and 36 + 6 weeks’) for each ethnic and deprivation postcode group, these were compared to white women from the least deprived 20% of areas. We iteratively developed the model, adjusting for covariates associated with preterm birth. A post-hoc calculation identified the rate of preterm birth for each ethnic group at each level of deprivation. Results We identified 1,111,045 livebirths between April 2018 and March 2021. The rate of preterm birth increased with socioeconomic deprivation and was highest at 7.1% per 100 livebirths (95%CI:7.00-7.20) in women living in the 20% most deprived areas, compared to 5.6% (95%CI:5.50-5.74) in women in the 20% least deprived areas. White women had the lowest preterm birth rate at 6.5% (95%CI:6.47-6.58) and South Asian women had the highest rate at 6.9% (95%CI:6.76-7.04) (Table 2). The rate of preterm birth increased according to increased area-level deprivation across all ethnic groups. In areas of high deprivation, the preterm birth rate was similar across ethnic groups. Whereas in less deprived areas, there were marked inequalities between ethnic groups. Conclusions Inequalities in preterm birth remain, despite overall decreases in preterm birth. We found area deprivation and individual ethnicity interact to increase the risk of preterm birth in marginalized communities. Interventions need to holistically consider the structural and socioenvironmental determinants of preterm birth. Key messages • Area deprivation and ethnicity remain key drivers of inequalities in preterm birth, despite overall decreases in preterm birth. • To reduce inequalities tailored prevention strategies are needed to address socioenvironmental and structural determinants of preterm birth in high deprivation areas and minoritized ethnicity groups.

Where should health system investments be made to protect the mental health of healthcare workers?

Abstract Background This study explores trends and work-related determinants of mental health and wellbeing among health and care workers in Europe since the COVID-19 pandemic. The aim is to determine where investments can best be made to protect and support mental health and wellbeing among health and care workers to improve retention and recruitment. Methods Data are analysed from the National Health Service staff survey in England and the Health Service Executive ‘Your Opinion Counts’ survey in Ireland to explore trends in mental health and wellbeing and burnout. Evidence is then taken from a series of European Observatory policy briefs, based on expert-led literature reviews, to explore determinants of poor mental health and wellbeing and to identify potential areas for investment. Results Rates of burnout and poor mental health and wellbeing have increased in England and Ireland since the start of the pandemic among all professional groups. Workplace-based factors are important determinants of poor mental health and wellbeing, and can be grouped into: macro-level structural factors such as staff shortages, poor working conditions and low pay; meso-level organisational factors including poor leadership, and insufficient education, training and support; micro-level individual factors such as insufficient self-care or not seeking support. However, determinants at the micro-level, especially seeking support from others, are largely shaped by structural or organisational factors. Conclusions Increased financing to address structural and organisational determinants of mental health and wellbeing contributes to improved patient care, better staff experience, lower rates of absenteeism, and enhanced recruitment and retention. It is therefore one of the best health system investments that can be made.

How do communities define “work precarity” and “labour exploitation”? Lessons for research from participatory research in high economic hardship communities in Chicago, Illinois/USA

Abstract Labour migration has both social and economic drivers that channel workers into jobs that are less desirable to citizens of the receiving countries. Immigrant workers find jobs through contacts from their home countries, including temporary staffing companies. These workers tend to co-locate in segregated communities and coalesce in jobs that entail hard work, low wages, and limited social benefits. As such, labour migration adds a dimension to the structural and social determinants of health (SDOH) that can broaden our understanding of health inequities, and that can point us toward policies and practices to enhance the health and wellbeing of migrant workforces. However, to generate evidence, align interventions with workers’ needs and priorities, and move evidence to action, it is crucial to engage communities. This presentation describes a community-university research partnership that co-investigates the relationship between work and health as experienced at the community level in two high-economic-hardship neighbourhoods in Chicago, Illinois/USA. The academic and practice partners co-developed and tested a conceptual model of the interrelations among migration, work and health, conducted an inventory of local employers, and executed a street-level survey of 497 workers in these two communities. The research findings helped enhance existing models of the structural/social determinants of health and of work precarity, thus informing methodological approaches to measure work precarity, labour exploitation, and their health effects. The community-based participatory research further led to several action-research projects that are ongoing. This presentation will describe the development of the community-university research partnership and its work, the subsequent enhancements made to the worker precarity and SDOH models, and preliminary findings of the partnership’s current action-research projects.

Maternal employment characteristics as a structural social determinant of breastfeeding duration

Abstract Background The European Region exhibits the world’s lowest exclusive breastfeeding rate at 6 months. Addressing work-related breastfeeding challenges is crucial, particularly for women navigating precarious work situations, compounding their adversity. This scoping review surveys research on maternal employment characteristics facilitating breastfeeding continuation post-return to work in the European Region. Methods Studies from 2013 to 2023 were gathered from Scopus, PubMed, and PsycInfo. Inclusion criteria comprised English or French quantitative/qualitative studies exploring links between maternal employment characteristics and breastfeeding status, duration, or experience. Participants were employed mothers of healthy children sustaining breastfeeding post-resumption of work. Key determinants included work-related factors contributing to socially diverse working conditions, encompassing type of employment, working conditions, and work environment. Geographic scope included World Health Organization European Region countries. Results Among 693 hits, 13 studies met criteria. Eight focused on work and breastfeeding, others explored broader breastfeeding determinants. Represented countries: Spain (n = 4), France (n = 4), UK (n = 2), Ireland (n = 2), Netherlands (n = 1). Findings highlighted methodological heterogeneity, indicating a lack of conceptual framework linking work, breastfeeding, and social health inequalities. Nonetheless, self-employment, non-manual professions with time flexibility, workplace breastfeeding facilities, coworker support, and breastfeeding workplace policies emerged as pivotal factors supporting working mothers’ breastfeeding. Conclusions Backing breastfeeding choices for working mothers is crucial amid adversities faced by mothers and children. These results underscore the need for targeted workplace interventions, including time flexibility, breastfeeding facilities, and promotion of breastfeeding-friendly policies. Key messages • Self-employment, non-manual occupations, time flexibility, breastfeeding facilities, support of co-workers and breastfeeding workplace policies promote continuation of breastfeeding. • Policy directives targeting low skilled or precarious jobs are needed to reduce social health inequalities broadly, and in particular, in relation to breastfeeding practices.

Preferential Binding of Cations Modulates Electrostatically Driven Protein Aggregation and Disaggregation.

Protein aggregation resulting in either ordered amyloids or amorphous aggregates is not only restricted to deadly human diseases but also associated with biotechnological challenges encountered in the therapeutic and food industries. Elucidating the key structural determinants of protein aggregation is important to devise targeted inhibitory strategies, but it still remains a formidable task owing to the underlying hierarchy, stochasticity, and complexity associated with the self-assembly processes. Additionally, alterations in solution pH, salt types, and ionic strength modulate various noncovalent interactions, thus affecting the protein aggregation propensity and the aggregation kinetics. However, the molecular origin and a detailed understanding of the effects of weakly and strongly hydrated salts on protein aggregation and their plausible roles in the dissolution of aggregates remain elusive. In this study, using fluorescence and circular dichroism spectroscopy in combination with electron microscopy and light scattering techniques, we show that the ionic size, valency, and extent of hydration of cations play a crucial role in regulating the protein aggregation and disaggregation processes, which may elicit unique methods for governing the balance between protein self-assembly and disassembly.

Accumulation of F-actin drives brain aging and limits healthspan in Drosophila

The actin cytoskeleton is a key determinant of cell structure and homeostasis. However, possible tissue-specific changes to actin dynamics during aging, notably brain aging, are not understood. Here, we show that there is an age-related increase in filamentous actin (F-actin) in Drosophila brains, which is counteracted by prolongevity interventions. Critically, decreasing F-actin levels in aging neurons prevents age-onset cognitive decline and extends organismal healthspan. Mechanistically, we show that autophagy, a recycling process required for neuronal homeostasis, is disabled upon actin dysregulation in the aged brain. Remarkably, disrupting actin polymerization in aged animals with cytoskeletal drugs restores brain autophagy to youthful levels and reverses cellular hallmarks of brain aging. Finally, reducing F-actin levels in aging neurons slows brain aging and promotes healthspan in an autophagy-dependent manner. Our data identify excess actin polymerization as a hallmark of brain aging, which can be targeted to reverse brain aging phenotypes and prolong healthspan.