Adult Life Course Research Articles

Body fatness across the adult life course and ovarian cancer risk.

Excess body fatness in late adulthood has been observed to increase ovarian cancer risk, but the association is relatively weak. Body fatness can change over time, and timing may differently influence risk. We used a life course epidemiology approach to identify whether the relation between body fatness and ovarian cancer risk is best described by a critical period, accumulation or sensitive period hypothesis. In a population-based case-control study of ovarian cancer in Montreal, Canada (2011-16), data on body mass index (BMI) at each decade starting at age 20 was available. Among 363 cases and 707 controls aged ≥ 50 years, we used a Bayesian relevant life course exposure model to estimate the relative importance of BMI for three pre-specified periods across the adult life course, i.e., early childbearing years, late childbearing years, and peri/postmenopause, on ovarian cancer risk. The accumulation hypothesis best described BMI in relation to ovarian cancer overall, with an odds ratio (OR) for the lifetime effect of BMI (per 5kg/m2 increase) of 1.10 (95% credible interval [CrI]: 0.90-1.35). For invasive ovarian cancer, the OR (95% CrI) for the lifetime effect was 1.16 (0.92-1.48), with BMI during early childbearing years showing the highest relative importance, suggesting this may be a sensitive period. For borderline cancer, the lifetime effect OR was not strongly supportive of an association (OR: 0.90, 95% CrI: 0.53-1.32). The results suggest that a sensitive period of early childbearing years is a candidate hypothesis for further investigation.

Soft skills and their relationship with life satisfaction and cognitive reserve in adulthood and older age

Soft skills are key factors for success in multiple contexts of daily life, as well as for life satisfaction, but little is known about their role in late adulthood and older age. In this study, we aimed to investigate the relationships of soft skills, as defined by the World Economic Forum, with two indicators of successful/healthy aging: life satisfaction and cognitive reserve. A sample of 435 adults aged 50 and over completed self-reported measures of soft skills, life satisfaction, and cognitive reserve. As control, fluid (reasoning) and crystalized (vocabulary) intelligence were assessed too, along with socio-demographic characteristics. A series of regression analyses showed that soft skills were positively related to both life satisfaction and, to a lower extent, cognitive reserve, above and beyond gender, age, and both fluid and crystallized intelligence. Interestingly, these associations were independent from participants’ age. Overall, these results highlight the importance of considering soft skills also over the middle-late adult life course, due to the potential role of these individual qualities in supporting an individual’s well-being and an active and engaged lifestyle, with implications for the promotion of a healthy aging.

Educational inequalities in blood pressure across the adult life course: Evidence from a 20-year follow-up study.

High blood pressure (BP) is a key contributor to the burden of disease. This study aimed to assess: a) educational differences across the entire BP distribution, and b) educational differences in the trajectories of BP across the adult life course. Longitudinal data from the Stockholm Diabetes Prevention Program was analysed using quantile regression and linear mixed effects models. Models were adjusted for age, sex, lifestyle, and BP medication. Lower educational level was associated with higher systolic BP (SBP) at all follow-up periods. Age and sex adjusted mean SBP was 2.49 (95% confidence interval (CI) 1.10, 3.87), 3.95 (95% CI 2.45, 5.45) and 2.61 (95% CI 1.09, 4.13) mmHg higher for people with pre-secondary education compared with post-secondary at baseline, 10 years and 20 years follow-up, respectively. Quantile regressions revealed that the inequalities could be observed across the entire BP continuum. Longitudinally analysed, people with pre-secondary education had 3.01 (95% CI 1.91-4.11) mmHg higher SBP than those with post-secondary education, age and sex adjusted. No significant convergence or divergence of the educational gaps in SBP was observed. Educational differences remained even after adjusting for lifestyle and BP medication. These results imply that public health interventions should aim to bring about distributional shifts in blood pressure, rather than exclusively focusing on hypertensive people, if they are to effectively minimize the educational disparities in blood pressure and its consequences.

Adulthood adiposity affects cardiac structure and function in later life.

Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. A total of 1690 participants in the National Survey of Health and Development birth cohort underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60-64 years. The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/e', e', and left atrial volume indexed to body surface area; systolic: ejection fraction, S', and myocardial contraction fraction) was investigated using multivariable linear regression models. Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60-64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60-64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60-64 years. Similar relationships were observed for WHR from age 43 years onwards. Higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of adiposity in later life.

Linking sequences of exposure to residential (dis)advantage, individual socioeconomic status, and health

Life course theories suggest that the relationship between residential (dis)advantage and health is best understood by examining the ordering and duration of cumulative exposures across the life course. This study employs sequence and cluster analysis on two decades of residential histories linked to the Survey of the Health of Wisconsin to define typologies of exposure to residential (dis)advantage and use these typologies to predict self-rated fair/poor health. Exposure to residential (dis)advantage is mostly stable across the adult life course and greater disadvantage predicts fair/poor health. Longitudinal exposures to residential (dis)advantage shape health independently of and in tandem with individual-level resources.

Adoption in the Era of Secrecy: Practical and Ethical Challenges Facing Adult Adoptees in the Search for Birth Families

This article explores findings from research into the impact of adoption throughout the life course of adults who were adopted in the era of secrecy, the 1940s–1970s. A narrative approach was used to explore their reflections, and semi-structured interviews were undertaken with 11 adults. The findings were then analysed through the lens of the Life Course Perspective. Previous studies on adoption have largely explored the outcomes of searching for birth family members, but few have focused on how adoptees went about this, the challenges they encountered, the decisions made and what happened as they began to dismantle layers of secrecy surrounding their adoption. For most of the participants, resources such as genealogical websites and particular guidance were not available at the time they were searching for birth information or attempting to make contact with birth families. Their accounts highlighted how social workers with potential birth information did not appear to be able to consider the broader emotional impact this might entail for adoptees. Initial meetings were described by some adoptees as hurdles to be overcome, and little birth information was given. Some continued to search for birth relatives without support, using random methods to gain contact. The ways in which adults went about their search sometimes appeared to suggest a lack of consideration or awareness on their part of the possible impact on others involved. In reality, they were faced with obstacles and barriers as they attempted to learn about their origins. Their stories provide a valuable insight into how adult adoptees sought to dismantle layers of secrecy, highlighting the complex, challenging and isolated situation they found themselves in as they searched for birth information and birth families, as well as the ethical challenges and dilemmas they had to negotiate in order to do so.

Education, employment, and care work over adulthood: gendered life course trajectories in Canada and Germany

ABSTRACT This article compares the education, employment, and care work biographical sequences of Canadian and German women and men from late adolescence into mid-adulthood. Through the lenses of comparative gendered life course theory and welfare regime theory, sequence and cluster analyses are used to determine the adult life course sequences of women and men in each country and to assess the extent to which they differ across contexts. The analyses reveal clear gender differences in work–family balance in labour market participation and unpaid care work. Groups also differ strongly on educational attainment, income, and family composition. Comparatively, gender differences are less marked in the Canadian context. These results suggest that differing gendered trajectories result in diverse outcomes depending on the national context, shaping different outcomes for women cross-nationally. Our findings highlight how historical and contemporary country-specific welfare state policies support or hinder women as active and productive members of society.

Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood.

The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course. Data from 499 community-dwelling adults (63% female) aged 20-92years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O2max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum. Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age2×SB×MVPA: B=-7E-08, SE=3E-08, P<0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age2×MVPA: B=3E-06, SE=1E-06, P<0.05), chair-rise performance (age×MVPA: B=-9E-05, SE=4E-05, P<0.05) and V̇O2max (MVPA at 21years: B=3E-02, SE=7E-03, P<0.05; age×MVPA: B=-5E-04, SE=2E-04, P<0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age×SB: B=-1E-04, SE=6E-05, P<0.05) and chair-rise performance (age×SB: B=1E-05, SE=7E-06, P<0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific. This cross-sectional study demonstrated that reduced sedentary time and increased activity duration were independently and synergistically associated with an attenuated age-related loss in physical capacity. These findings need to be confirmed with longitudinal data but encourage both adopting an active lifestyle and reducing sedentary time as preventive measures against physical aging.

The interplay of depression symptoms and physical activity: Bidirectional insights from 25-years of the Americans' changing lives panel

BackgroundDepression symptomology (DSx) and insufficient Physical Activity (PA) are among the leading causes of illness, and major contributors to global public health burden. Reviews and meta-analyses indicate that DSx and PA cause each other, yet most studies conducted use data and analyses which cannot specify their bidirectional associations across the life course. MethodThe present study estimates dynamic panel models with fixed effects through structural equation models with full-information maximum likelihood estimation (ML-SEM) based on 5 waves (1986–2011) of the Americans' Changing Lives (ACL) panel. This is a nationally representative probability sample of 3499 non-institutionalized U.S. adults ages 25 and older in 1986. Respondents participated in an average of 3.29 waves, with 67.84% participating in at least 3 waves, and 27.26% participating in all 5 waves. Models adjust for age, partner status, social integration, activity limitations, and serious financial problems. Data are available from the ICPSR (4690). ResultsEstimates from ML-SEM reveal negative and significant bidirectional cross-sectional associations between DSx and PA. Models also indicate a negative and significant cross-lagged association from DSx to PA, but not from cross-lagged PA to DSx. On both sides, earlier levels are significantly associated with future levels of PA and DSx. ConclusionsThis study is the first to use a causal inference technique which adjusts for all time-invariant confounders while modelling the bidirectional linkages between depression symptoms and physical activity over 25-years of adulthood. It supports literature showing a consistent cross-sectional relationship, and advances understanding on how DSx earlier in the adult life course may influence PA as people age.

A Perspective on Auditory Wellness: What It Is, Why It Is Important, and How It Can Be Managed.

During the last decade, there has been a move towards consumer-centric hearing healthcare. This is a direct result of technological advancements (e.g., merger of consumer grade hearing aids with consumer grade earphones creating a wide range of hearing devices) as well as policy changes (e.g., the U.S. Food and Drug Administration creating a new over-the-counter [OTC] hearing aid category). In addition to various direct-to-consumer (DTC) hearing devices available on the market, there are also several validated tools for the self-assessment of auditory function and the detection of ear disease, as well as tools for education about hearing loss, hearing devices, and communication strategies. Further, all can be made easily available to a wide range of people. This perspective provides a framework and identifies tools to improve and maintain optimal auditory wellness across the adult life course. A broadly available and accessible set of tools that can be made available on a digital platform to aid adults in the assessment and as needed, the improvement, of auditory wellness is discussed.

Comorbidity Clusters Among Adults With Cerebral Palsy: A Latent Class Analysis

IntroductionAdults with cerebral palsy (CP) are at risk for early multi-morbidity onset, but little is known about the composition of multi-morbidity profiles or how these profiles present across adulthood. The objective of this study was to identify multi-morbidity profiles and association with mortality among adults with CP. MethodsThis retrospective cohort study used a random 20% fee-for-service Medicare database from 01/01/2008-12/31/2019 from adults ≥18 years old with CP. Latent class analyses using four-class models were conducted within each age cohort (young adults 18-39, middle adulthood 40-64, and older adults ≥65 years) to determine patterns of 30 comorbidities defined using ICD-9 codes, identified from 01/01/2008-12/31/2010, and their association with mortality through 12/31/2019 (up to 11 years of follow-up); statistical analysis was performed in 2023. ResultsThree classes were relatively consistent in the composition of comorbidities across young (n=7,020), middle (n=13,554), and older (n=4,193) cohorts: (1) “Low Morbidity” (low proportion of all comorbidities) representing 50.1% (young), 41.4% (middle), and 30.9% (older) of the cohorts; (2) “Neurological Multi-Morbidity” (e.g., epilepsy, intellectual disabilities) representing 26.0% (young), 26.6% (middle), and 14.7% (older); and “Complex Multi-Morbidity” (e.g., cardiorespiratory, nutritional, musculoskeletal, neurological) representing 26.0% (young), 26.6% (middle), and 14.7% (older). The fourth class varied by young (“Mental Health Disorders”), middle (“Hypertension”), and older (“Hypertension and Osteoarthritis”) age cohorts. Compared to the “Low Morbidity” class, other classes had an increased mortality rate for each age cohort (HR range, 1.34-5.58, all P<0.001). ConclusionsFindings provide insight into varied multi-morbidity profiles and associations with mortality across the life course for adults with CP.

Person-centred integrated care? Looking beyond contemporary needs, wishes and goals. A workshop on the importance of working from a life course perspective in caring neighbourhoods.

Background: The importance of a life course perspective is often not taken into account when detecting the needs, wishes and goals of older adults. Research and practice to date has tended to focus on the 'now'. However, adapting a life-course perspective in person-centred care and caring neighbourhoods could enrich and deepen our understanding of current needs, wishes and goals.&#x0D; Aim: The aim of this workshop is to give insight into the use of a life-course approach in relation to research and practice on person-centred integrated care and caring neighbourhoods. It aims to enthuse participants in using a life-course approach in their future academic and professional work.&#x0D; Participants: This workshop is important for a variety of actors: researchers, practitioners, politicians, older adults. Experience with the subject is not mandatory. The presence of a diverse group enriches our discussions and reflections.&#x0D; Methods:&#x0D; 1.Introduction: The presentation will start with some questions toward the participants. The answers will lead to a presentation of 5 minutes on the use of a life course approach in relation to person-centred integrated care and caring neighbourhoods. (10min)&#x0D; 2.Inspirational presentations: Four examples will be given of how a life-course approach can be used throughout 4 different themes: housing, civic engagement, care and the neighbourhood. Presentations will be interactive. (40min)&#x0D; &#x0D; Ariane Vanbellinghen studies housing and wellbeing through the life-course of older adults. Housing is an essential part in caring neighbourhoods, especially for older adults, where there is often a certain resistance to remodel their current home or relocate.&#x0D; Bas Dikmans focuses on civic engagement of older adults in disadvantaged neighbourhoods, making use of a life course perspective in his research to see how life events facilitate or pose obstacles to civic engagement in later life.&#x0D; &#x0D; &#x0D; &#x0D; Mikis Dormaels is a life story writer with the senior care team, part of the Center for Mental Health in Brussels. In 2010, "narrative care" as a treatment method was developed and offered to older people in a vulnerable position.&#x0D; Liesbeth De Donder will open the discussion on how to include neighbourhood life stories, as an addition to individual stories, when developing caring neighbourhoods.&#x0D; &#x0D; 3.Round tables: exercises on using a life-course approach (30 min)&#x0D; 4 workshops will be organised. Participants are free to choose which workshop to attend: 1) housing through the life-course, 2) civic engagement through the life-course, 3) narrative care: life stories in mental care and 4) life stories as a neighbourhood mapping tool. &#x0D; We will interact with the audience trough specific exercises on using a specific method, what the benefits and challenges of the method are, how they can integrate it in their own context. Together with the group input, feedback, and own experiences, among others, knowledge will be co-created.&#x0D; Closing: Plenary reflection and summary (10 min)&#x0D; In a plenary session, all the main findings that were collected through the workshop will be shared and a representative of each workshop will summarise the key-messages to take home.&#x0D;

LONELINESS AMONG INVOLUNTARILY CHILDLESS OLDER ADULTS: A LIFE COURSE PERSPECTIVE

Abstract To this day, having children is seen as the norm, and the consequences in later life when a child wish is not fulfilled are rarely addressed. Therefore, this study investigates the reasons for involuntary childlessness as well as the relationship with potential feelings of loneliness throughout the life course of older adults. Data were collected through individual life story interviews using the McAdams life story interview (N=15) with involuntary childless adults older than 60 living in Belgium. Using a thematic analysis, the results firstly indicate that respondents expressed several reasons for their involuntary childlessness, such as medical reasons, advancing age, career choices and opportunities, partner status and traumas during the life course. Secondly, involuntary childlessness impacts negatively on individual well-being on the one hand, by experiencing feelings of emptiness and deficiency, but on the other hand, having more free time and flexibility during the life course within the social network is perceived as positive. Thirdly, from the moment people realized they would never have children, feelings of loneliness arose. Also, once peers did have (grand)children, or during holiday seasons (e.g., Christmas Day), loneliness feelings became more prevalent compared to earlier in life. However, feelings of loss and emptiness (e.g., missing someone to pass on norms and values to) prevailed over loneliness feelings. The discussion highlights the extent to which older people pick up where they left off and constitute their lives meaningfully at various levels (i.e., at individual level and regarding social relations) when their child wish was never fulfilled.

Predicting depression in old age: Combining life course data with machine learning

With ageing populations, understanding life course factors that raise the risk of depression in old age may help anticipate needs and reduce healthcare costs in the long run. We estimate the risk of depression in old age by combining adult life course trajectories and childhood conditions in supervised machine learning algorithms. Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we implement and compare the performance of six alternative machine learning algorithms. We analyse the performance of the algorithms using different life-course data configurations. While we obtain similar predictive abilities between algorithms, we achieve the highest predictive performance when employing semi-structured representations of life courses using sequence data. We use the Shapley Additive Explanations method to extract the most decisive predictive patterns. Age, health, childhood conditions, and low education predict most depression risk later in life, but we identify new predictive patterns in indicators of life course instability and low utilization of dental care services.

Re-conceptualizing music education in the older adult life course: A qualitative meta-synthesis

The Seoul Agenda by UNESCO has set goals to develop arts education, ensuring that learners from all social backgrounds have lifelong access to arts education in a wide range of community and institutional settings. However, the purpose of lifelong learning for individuals beyond labor-market age has been largely overlooked, making it challenging to convince institutions, funders, and policymakers of its worth. The value accorded to the complex forms of lifelong learning in later life and the widely recognized health impacts of music on aging body and brain are the principal considerations to take into account when studying the effects of music education on older adults. In this study, we address the state-of-the-art research concerning older adults and music education in studies published in major peer-reviewed music education journals since the Seoul Agenda by UNESCO. We present the findings from a systematic literature review, followed by a qualitative meta-synthesis, focusing on the values, beliefs, and key concepts conveyed in the included studies. The findings of this study indicate that older adults are often portrayed narrowly and stereotypically, corroborating the issues in the sociology of aging. Our study highlights insights into the conceptualizations of music learning and participation in later life course and what these might mean for the policy and practice of later-life music education and the educational opportunities for older adults more broadly.

Examining Aspects of Digital Inclusion Among National Samples of US Older Adults

We live in a world where we are constantly connected to devices (e.g., smartphones, computers, tablets) and are encouraged to go online to find information about most things in society. This constant digital connection provides the means whereby many individuals communicate and exchange social support. For most demographic groups, this results in being online and connected to devices multiple times each day. Older adults have been slower to adopt and use emerging information and communication technologies (ICTs). Their digital divide in comparison to other age groups may not be an accurate representation of their technology use and the reasons for this use. This descriptive study examines this view of digital inclusion by focusing on older adults and their uses of technology. We provide an overview of technology usage by different older adult age groups in the United States using existing national‐level data. We utilize life course and aging theoretical perspectives to help articulate how older adults use a wide variety of ICTs and whether they are constantly connected, and we note that while a constant connection to devices may be normative for younger age groups, this may not, and perhaps should not, be the case for older adults. The article concludes with a discussion of the social construction of digital inclusion and emphasizes the significant variation that exists in this construct, measurement of technology use in large‐scale datasets, and variation in technology use across older adult life course groups.

Life-course insecurity among young adults: Evidence for variation by employment status?

Previous research suggests that lack of employment security can lead young adults to experience a higher degree of insecurity with regard to their future life. We test the relationship between life-course insecurity, i.e. worrisome feelings with regard to one's own future, and young adults' employment status using a newly developed measurement instrument. Furthermore, we examine whether, in terms of life-course insecurity, specific groups of young people are more affected by insecure employment conditions based on their structural position. Survey data (n=1087) were collected within a Dutch representative panel among those aged 18-35. Structural equation modelling is used to construct latent dependent variables for experienced insecurity in four life domains, namely 'work', 'finances', 'partner and family' and 'leisure and personal development'. Results show that, while controlling for gender, life phase, education level and level of neuroticism, lack of employment is associated with higher insecurity in all four domains of life. Precarious employment based on a flexible contract is associated with higher insecurity regarding 'work', 'finances' and 'partner and family'. Moreover, we find the relationship between lack of employment and life-course insecurity to be stronger for young people in the 26-35 age bracket. However, higher educational attainment does not attenuate the positive relationship between precarious employment and life-course insecurity. The findings of this study inform our theoretical understanding of agency within the life course of young adults by signaling insecure labour market attachment as a potential constraint to formulating plans for the future.

The personal curriculum: conceptions, intentions and enactments of learning across working life

ABSTRACT The concept of curriculum as a personal journey is now timely, yet timeless and pertinent as an explanatory basis for understanding learning and development across the lifespan. It addresses a current need to explain adults’ learning across working life when achieving individual, occupational, community, and societal goals. Advancing this explanation necessitate elaborating how that learning is realised and can be supported educatively. This conceptual paper presents and discusses the concept of personal curriculum to illuminate and explain pathways of adults’ learning and developmental experiences across working lives. It offers a perspective of curriculum as a personal, rather than an institutional phenomenon. It also extends the concept of ‘experienced curriculum’ beyond periodic episodes of engagement in educational programmes to capture the continuity of educative experiences across the adult life course. Importantly, this concept liberates curriculum from the constraints of something intended, enacted and appraised within specific social settings (e.g. educational and work settings) to be more inclusive of the totality of learners’ experiences. The case is made for its conceptual, theoretical and practical salience beyond a focus on institutional imperatives. Drawing upon empirical work on how working age adults sustain their employability across working lives, this conception extends discussions about what constitutes curriculum, to encapsulate the learning pathways individuals take across working life.

Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegans

Living longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic.

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.

Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (β=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (β=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (β= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (β=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (β=0.07, 95%CI [0.00, 0.15]. Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.