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Abstract Physiological stress levels in response to sexual behavior stigma among men who have sex with men (MSM) in the United States (US) are understudied. The current study aims to explore the relationship between sexual behavior stigma and salivary cortisol both overall and stratified by race/ethnicity. If such an association exists, it may suggest that sexual behavior stigma can be physiologically measured or indicated by the presence of heightened salivary cortisol. A subsample of 667 MSM participants from the 2019 American Men’s Internet Survey (AMIS; N = 10,129) submitted morning (AM) and evening (PM) saliva cortisol samples using at-home mail-in collection kits. Average daily cortisol and daily cortisol change were calculated; simple linear regressions estimated associations between cortisol measures and sexual behavior stigma characterized in four different ways (ever and recent experience of individual stigma items; average ever and recent experience of three stigma scales: stigma from family and friends, anticipated healthcare stigma, general social stigma). Participants reported a mean age of 36.0 years (SD = 14.9), with most being non-Hispanic white (n = 480, 72.0%), Hispanic (n = 164, 12.3%), or Black/African American (n = 146, 10.9%), and identified as homosexual/gay (n = 562, 84.3%). Reporting ever experiencing healthcare providers gossiping was significantly associated with higher PM cortisol (β = 0.12, p = 0.001) and higher average daily cortisol (β = 0.11, p = 0.004), while reporting ever experiencing police refusing to protect was associated with higher AM cortisol (β = 0.08, p = 0.03) and higher average daily cortisol (β = 0.09, p = 0.02). Recent experiences of stigma were not significant predictors of any measure of cortisol. Measures of salivary cortisol may be used to characterize sexual behavior stigma among MSM populations, however more insight is needed to determine its exact relationship and strength.

Abstract Background Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. Results Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p

Abstract Background Frailty assessment promises to identify older adults at risk for adverse consequences following stressors and target interventions to improve health outcomes. The Physical Frailty Phenotype (PFP) is a widely-studied, well validated assessment but incorporates performance-based slow walk and grip strength criteria that challenge its use in some clinical settings. Variants replacing performance-based elements with self-reported proxies have been proposed. Our study evaluated whether commonly available disability self-reports could be substituted for the performance-based criteria in the PFP while still identifying as “frail” the same subpopulations of individuals. Methods Parallel analyses were conducted in 3393 female and 2495 male Cardiovascular Health Study, Round 2 participants assessed in 1989–90. Candidate self-reported proxies for the phenotype’s “slowness” and “weakness” criteria were evaluated for comparable prevalence and agreement by mode of measurement. For best-performing candidates: Frailty status (3 + positive criteria out of 5) was compared for prevalence and agreement between the PFP and mostly self-reported versions. Personal characteristics were compared between those adjudicated as frail by (a) only a self-reported version; (b) only the PFP; (c) both, using bivariable analyses and multinomial logistic regression. Results Self-reported difficulty walking ½ mile was selected as a proxy for the phenotype’s slowness criterion. Two self-reported weakness proxies were examined: difficulty transferring from a bed or chair or gripping with hands, and difficulty as just defined or in lifting a 10-pound bag. Prevalences matched to within 4% between self-reported and performance-based criteria in the whole sample, but in all cases the self-reported prevalence for women exceeded that for men by 11% or more. Cross-modal agreement was moderate, with by-criterion and frailty-wide Kappa statistics of 0.55–0.60 in all cases. Frail subgroups (a), (b), (c) were independently discriminated (p

Abstract Background The ability to identify frail older adults using a self-reported version of the physical frailty phenotype (PFP) that has been validated with the standard PFP could facilitate physical frailty detection in clinical settings. Methods We collected data from volunteers (N = 182), ages 65 years and older, in an aging research registry in Baltimore, Maryland. Measurements included: standard PFP (walking speed, grip strength, weight loss, activity, exhaustion); and self-reported questions about walking and handgrip strength. We compared objectively-measured gait speed and grip strength to self-reported questions using Cohen’s Kappa and diagnostic accuracy tests. We used these measures to compare the standard PFP with self-reported versions of the PFP, focusing on a dichotomized identification of frail versus pre- or non-frail participants. Results Self-reported slowness had fair-to-moderate agreement (Kappa(k) = 0.34–0.56) with measured slowness; self-reported and objective weakness had slight-to-borderline-fair agreement (k = 0.10–0.21). Combining three self-reported slowness questions had highest sensitivity (81%) and negative predictive value (NPV; 91%). For weakness, three questions combined had highest sensitivity (72%), while all combinations had comparable NPV. Follow-up questions on level of difficulty led to minimal changes in agreement and decreased sensitivity. Substituting subjective for objective measures in our PFP model dichotomized by frail versus non/pre-frail, we found substantial (k = 0.76–0.78) agreement between standard and self-reported PFPs. We found highest sensitivity (86.4%) and NPV (98.7%) when comparing the dichotomized standard PFP to a self-reported version combining all slowness and weakness questions. Substitutions in a three-level model (frail, vs pre-frail, vs. non-frail) resulted in fair-to-moderate agreement (k = 0.33–0.50) with the standard PFP. Conclusions Our results show potential utility as well as challenges of using certain self-reported questions in a modified frailty phenotype. A self-reported PFP with high agreement to the standard phenotype could be a valuable frailty screening assessment in clinical settings.

Abstract Background We aimed to study whether physical frailty and cognitive impairment (CI) increase the risk of recurrent hospitalizations in older adults, independent of comorbidity, and disability. Methods Two thousand five hundred forty-nine community-dwelling participants from the National Health and Aging Trends Study (NHATS) with 3 + years of continuous Medicare coverage from linked claims data were included. We used the marginal means/rates recurrent events model to investigate the association of baseline CI (mild CI or dementia) and physical frailty, separately and synergistically, with the number of all-source vs. Emergency Department (ED)-admission vs. direct admission hospitalizations over 2 years. Results 17.8% of participants had at least one ED-admission hospitalization; 12.7% had at least one direct admission hospitalization. Frailty and CI, modeled separately, were both significantly associated with risk of recurrent all-source (Rate Ratio (RR) = 1.24 for frailty, 1.21 for CI; p

Abstract Background Aging metrics incorporating cognitive and physical function are not fully understood, hampering their utility in research and clinical practice. This study aimed to determine the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function and the associations of the three metrics with mortality. Methods We considered three existing aging metrics including the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them using data from the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazards regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. Results In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2, 16.6, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR) (95% confidence interval (CI)) 2.87 (1.74–4.74); FI, OR (95% CI) 1.94 (1.50–2.50); MCR, OR (95% CI) 1.27 (1.00–1.62)). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement and continuous net reclassification improvement (all P

Abstract Backgrounds Cardiovascular disease (CVD) risk factors are individually associated with frailty. This study examined whether Framingham CVD risk score (FRS) as an aggregate measure of CVD risk is associated with incident frailty among Chinese older adults. Methods This study used data from the China Health and Retirement Longitudinal Study. A sample of 3,618 participants aged 60 to 95 years and without CVD at baseline were followed for four years. FRS was calculated at baseline. Frailty status was defined as not-frail (0–2 criteria) or frail (3–5 criteria) based on the physical frailty phenotype consisting of five binary criteria (weakness, slowness, exhaustion, low activity level, and weight loss). After excluding subjects who were frail (n = 248) at baseline, discrete-time Cox regression was used to evaluate the relationship between FRS and incident frailty. Results During a median follow-up of 4.0 years, 323 (8 %) participants developed CVD and 318 (11 %) subjects had frailty onset. Higher FRS was associated with greater risk of incident frailty (HR: 1.03, 95 % CI: 1.00 to 1.06) after adjusting for education, marital status, obesity, comorbidity burden, and cognitive function. This association however was no longer significant (HR: 1.00, 95 % CI: 0.97 to 1.03) after additionally adjusting for age. These findings remained essentially unchanged after excluding subjects with depression (n = 590) at baseline or incident CVD (n = 323) during the 4-year follow-up. Conclusions The FRS was not independently associated with incident frailty after adjusting for chronological age. More research is needed to assess the clinical utility of the FRS in predicting adverse health outcomes other than CVD in older adults.

Abstract Background Frailty syndrome disproportionately affects older people, including 15% of non-nursing home population, and is known to be a strong predictor of poor health outcomes. There is a growing interest in incorporating frailty assessment into research and clinical practice, which may provide an opportunity to improve in home frailty assessment and improve doctor patient communication. Methods We conducted focus groups discussions to solicit input from older adult care recipients (non-frail, pre-frail, and frail), their informal caregivers, and medical providers about their preferences to tailor a mobile app to measure frailty in the home using sensor based technologies. Focus groups were recorded, transcribed, and analyzed thematically. Results We identified three major themes: 1) perspectives of frailty; 2) perceptions of home based sensors; and 3) data management concerns. These relate to the participants’ insight, attitudes and concerns about having sensor-based technology to measure frailty in the home. Our qualitative findings indicate that knowing frailty status is important and useful and would allow older adults to remain independent longer. Participants also noted concerns with data management and the hope that this technology would not replace in-person visits with their healthcare provider. Conclusions This study found that study participants of each frailty status expressed high interest and acceptance of sensor-based technologies. Based on the qualitative findings of this study, sensor-based technologies show promise for frailty assessment of older adults with care needs. The main concerns identified related to the volume of data collected and strategies for responsible and secure transfer, reporting, and distillation of data into useful and timely care information. Sensor-based technologies should be piloted for feasibility and utility. This will inform the larger goal of helping older adults to maintain independence while tracking potential health declines, especially among the most vulnerable, for early detection and intervention. Keywords: Frailty, wearable, health services.

Older adults are at risk of driving cessation as they age, which can result in negative health outcomes including loss of independence. This study aimed to investigate the associations of self-care health behaviors with the risk of driving cessation. Demographics, health and driving characteristics were captured from healthcare systems in Denver, CO, San Diego, CA, Ann Arbor, MI, Baltimore, MD and Cooperstown, NY for 2,990 adults at baseline then followed from July 2015 to January 2021 via in-person assessments and questionnaires. The follow-up accumulated a total of 7,348 person-years and 46 driving cessations, yielding an incidence rate of 0.63 per 100 person-years. Multivariable Cox proportional hazards regression was used to evaluate the relationship between self-care behaviors and driving cessation, stratified by gender, and accounting for multiple failure events and clustering by study site. Ability to participate in social roles and activities was associated with an 8% reduction in the risk of driving cessation [adjusted hazard ratio (HR): 0.92; 95% CI: 0.89, 0.94]. Increased participation in social activities and relationships is associated with driving longevity in older adults and should be targeted for interventions to maintain driving mobility.

Importance: Few studies have addressed the combined effects of health-promoting and self-care behaviors among older adults. Thus, new research is needed to assess the potential for behavior change to prolong independence in later life.Objectives: To determine the relationships between self-care behaviors and risks of mobility and activities of daily living (ADLs) over time.Design: Longitudinal data was used from the National Health and Aging Trends Study (NHATS) cohort. Eight baseline self-care behaviors were summarized using latent class analysis. Separately, longitudinal latent classes of mobility and ADLs were created.Setting: Annual in-person interviews conducted for a nationally representative sample.Participants: The baseline study sample included 7,609 Medicare beneficiaries aged ≥65 from NHATS who were living in community or residential care settings, with a 71% response rate. The average age was 75, with 57% female, 81% white and 78% high school graduates or higher. Approximately, 80% (n = 6,064) completed 5 years of follow-up.Exposures: Favorable vs. unfavorable self-care latent classes measured at baseline.Main outcomes and Measures: Associations were measured between baseline classes and longitudinal classes of mobility and ADLs difficulty. Among decedents, 5-year associations were measured between baseline classes and years of overall, healthy, able, and healthy/able life.Results: Two habitual baseline self-care behavioral patterns (46% favorable; 54% unfavorable) and three trajectories of change in mobility and ADLs disability (maintaining independence; shifting to accommodation/difficulty; shifting to assistance) emerged over time. Participants with a favorable baseline pattern had 92% (0.90–0.94) reduced risk in shifting to assistance class and 70% (0.64–0.76) reduced risk for shifting to accommodation/difficulty class for mobility disability. Participants with a favorable baseline pattern had 86% (0.83–0.89) reduced risk in shifting to assistance class and 24% (0.11–0.36) reduced risk in shifting to accommodation/difficulty class for ADLs disability. Those with an unfavorable pattern had 2.54 times greater risk of mortality by the end of the 5-year follow-up compared to those with a favorable pattern.Conclusion: Self-care behaviors in older age represent a habitual pattern. A favorable self-care behavioral pattern decreased the risk of moving towards a more disabled profile and added years of life. Interventions should encourage self-care behaviors constituting a favorable pattern.

Many older adults receive routine cancer screening even when it is no longer recommended. We sought to identify demographic, health-related, and attitudinal factors that are most predictive of continued breast, colorectal, and prostate cancer screening decisions in older adults under various scenarios. A sample of adults age 65+ (n = 1272) were recruited from a nationally representative panel in November 2016, of which 881 (69.3%) completed our survey. Participants were presented vignettes in which we experimentally varied a hypothetical patient's life expectancy, age, quality of life, and physician screening recommendation. The dependent variable was the choice to continue cancer screening in the vignette. Classification and regression tree (CART) analysis was used to identify characteristics most predictive of screening decisions; both the participants' characteristics and the hypothetical patient's characteristics in the vignettes were included in the analysis. CART analysis uses recursive partitioning to create a classification tree in which variables predictive of the outcome are included as hierarchical tree nodes. We used automated ten-fold cross-validation to select the tree with lowest misclassification and highest predictive accuracy. Participants' attitude towards cancer screening was most predictive of choosing screening. Among those who agreed with the statement “I plan to get screened for cancer for as long as I live” (n = 300, 31.9%), 73.2% chose screening and 57.2% would still choose screening if hypothetical patient had 1-year life expectancy. For this subset of older adults with enthusiasm towards screening even when presented with scenario involving limited life expectancy, efforts are needed to improve informed decision-making about screening. Keywords: Cancer screening, Life expectancy, Decision-making, CART analysis

Adolescent girls and young women (AGYW) aged 15 to 24 years face disproportionately high risks of acquiring HIV and other sexually transmitted infections (STIs). A sexual health risk stratification tool can support the development and implementation of tailored HIV and STI prevention services for sub-groups of at-risk AGYW. Data were collected among sexually active AGYW aged 15 to 24 years in Tanzania between April 2015 and March 2017. Exploratory and confirmatory factor analyses were conducted to construct and assess the latent structure of a ten-item scale for rapid assessment of sexual health risks. Items with high factor loadings and minimal cross loadings were retained in the final scale. Scale performance was appraised against condomless sex (defined as unprotected vaginal or anal intercourse) reported by AGYW for construct validity. A three-factor structure of vulnerability to HIV among AGYW was supported with subscales for socioeconomic vulnerability; lack of adult support; and sexual behavioral risks. The chi-square goodness-of-fit test, root mean square error of approximation, comparative fit index, and Tucker-Lewis index indicated a strong goodness-of-fit of the three-factor scale. Cronbach alphas (0.55 for socioeconomic vulnerability, 0.55 for lack of support, and 0.48 for sexual risk) indicated sub-optimal internal consistency for all sub-scales. The factor-item and factor-factor correlations identified in these analyses were consistent with the conceptual framework of vulnerability of HIV infection in AGYW, suggesting good construct validity. The scale also demonstrated a statistically significant association with condomless sex and could be potentially used for sexual health risk stratification (OR = 1.17, 95% CI: 1.12, 1.23). The sexual health and HIV risk stratification scale demonstrated potential in identifying sexually active AGYW at high risk for HIV and other STIs. Ultimately, all AGYW in Tanzania are not at equal risk for HIV and this scale may support directing resources towards those at highest risk of HIV.

BACKGROUND Physical frailty in older individuals is characterized by subjective symptoms of fatigue and exercise intolerance (EI). Objective abnormalities in skeletal muscle (SM) mitochondrial high-energy phosphate (HEP) metabolism contribute to EI in inherited myopathies; however, their presence or link to EI in the frail older adult is unknown.METHODS Here, we studied 3 groups of ambulatory, community-dwelling adults with no history of significant coronary disease: frail older (FO) individuals (81 ± 2.7 years, mean ± SEM), nonfrail older (NFO) individuals (79 ± 2.0 years), and healthy middle-aged individuals, who served as controls (CONT, 51 ± 2.1 years). Lower extremity SM HEP levels and mitochondrial function were measured with 31P magnetic resonance (MR) techniques during graded multistage plantar flexion exercise (PFE). EI was quantified by a 6-minute walk (6MW) and peak oxygen consumption during cardiopulmonary testing (peak VO2).RESULTS During graded exercise, FO, NFO, and CONT individuals all fatigued at similar SM HEP levels, as measured by 31P-MR. However, FO individuals fatigued fastest, with several-fold higher rates of PFE-induced HEP decline that correlated closely with shorter exercise duration in the MR scanner and with 6MW distance and lower peak oxygen consumption on cardiopulmonary testing (P < 0.001 for all). SM mitochondrial oxidative capacity was lower in older individuals and correlated with rapid HEP decline but less closely with EI.CONCLUSION Several-fold faster SM energetic decline during exercise occurs in FO individuals and correlates closely with multiple measures of EI. Rapid energetic decline represents an objective, functional measure of SM metabolic changes and a potential new target for mitigating frailty-associated physical limitations.FUNDING This work was supported by NIH R21 AG045634, R01 AG063661, R01 HL61912, the Johns Hopkins University Claude D. Pepper Older Americans Independence Center P30AG021334, and the Clarence Doodeman Endowment in Cardiology at Johns Hopkins.

Chronic inflammation is associated with physical frailty and functional decline in older adults; however, the molecular mechanisms of this linkage are not understood. A mouse model of chronic inflammation showed reduced motor function and partial denervation at the neuromuscular junction. Metabolomic profiling of these mice and further validation in frail human subjects showed significant dysregulation in the tryptophan degradation pathway, including decreased tryptophan and serotonin, and increased levels of some neurotoxic kynurenines. In humans, kynurenine strongly correlated with age, frailty status, TNF-αR1 and IL-6, weaker grip strength, and slower walking speed. To study the effects of elevated neurotoxic kynurenines on motor neuronal cell viability and axonal degeneration, we used motor neuronal cells treated with 3-hydroxykynurenine and quinolinic acid and observed neurite degeneration in a dose-dependent manner and potentiation of toxicity between 3-hydroxykynurenine and quinolinic acid. These results suggest that kynurenines mediate neuromuscular dysfunction associated with chronic inflammation and aging.

Abstract Background Frailty has been recognized as an important medical syndrome in older adults. Growing literature supports the clinical application of frailty but US older adults’ perceptions of frailty have not been explored. We aim to examine perceptions and informational needs about frailty among older adults. Methods This was a qualitative study involving focus groups of community-dwelling older adults with diverse age and frailty status. We explored participants’ beliefs and knowledge about frailty and informational needs about frailty as a medical syndrome. Results The participants’ mean age was 76.3. Of the 29 participants, 21 (72%) were female, and 21 (72%) were white. We identified three major themes: 1) Older adults’ perceptions of frailty differed from the definition used in medical literature; they often perceived a psychological component to being frailty and some were skeptical of the syndromic definition based on multiple symptoms. 2) Compared to participants who were non-frail or pre-frail, participants who were frail were more receptive to discussing their frailty status with clinicians; 3) Participants wanted know about how to treat or prevent frailty and the risks associated with being frail. Many participants felt that these information can be conveyed without necessarily using the specific term “frail”, which they perceived to have a negative connotation. Conclusions Older adults, especially those who are frail, may be interested to discuss frailty as a medical syndrome. However, negative perceptions are associated with the term “frail” and may be a barrier to clinical application of frailty. Further research is needed to understand acceptable ways for communicating about frailty in clinical practice.

There is an integral research gap regarding whether there is a relationship between pain levels and low physical activity among older women. This is a secondary analysis of a longitudinal cohort study, the Women’s Health and Aging Study (WHAS) II. Our analyses included 436 community-dwelling women between the ages of 70 and 79, who were followed for 10.5 years. We employed marginal structural modeling, which controls for time-dependent confounding, with the aim of assessing the potential direct association between pain levels and low physical activity and assess a graded relationship. Compared to women with no pain, those with widespread pain were nearly half as likely to be moderately active versus low active (aOR: 0.46, 95% confidence interval (CI): 0.22, 0.96). A graded association was observed across the four pain levels (no pain or mild pain, other pain, moderate or severe lower extremity pain, and widespread pain) on low physical activity. Our findings indicate that reducing chronic widespread pain in older women may increase moderate physical activity, and therefore reduce the downstream health risks of low physical activity, including morbidity and mortality risk.

Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, older humans in measured parameters of glucose metabolism, oxygen consumption (VO2), respiratory quotient (RQ), spontaneous locomotor activity, body composition and plasma adipokine levels. To test this hypothesis, we investigated these metabolic parameters in cohorts of 3, 10, and 20 month old IL 10tm female mice and age and gender matched C57Bl/6 mice. Insulin sensitivity, glucose homeostasis, locomotor activity and RQ were not significantly altered between the two strains of mice. Interestingly, old IL 10tm mice had significantly decreased VO2 when normalized by lean mass, but not when normalized by fat mass or the lean/fat mass ratio. NMR based body composition analysis and dissection weights show that fat mass is decreased with age in IL 10tm mice compared to controls. Further, plasma adiponectin and leptin were also decreased in IL 10tm.These findings suggest that frailty observed in this mouse model of chronic inflammation may in part be driven by alterations in fat mass, hormone secretion and energy metabolism.

Anemia is common in older adults and associated with adverse health outcomes in epidemiological studies. A thorough understanding of the complex pathophysiological mechanisms driving anemia in the elderly is lacking; but inflammation, iron restriction, and impaired erythroid maturation are thought to influence the phenotype. We hypothesized that interleukin-6 contributes to this anemia, given its pro-inflammatory activities, its ability to induce hepcidin antimicrobial peptide, and its negative impact on several tissues in older adults. We tested this hypothesis by comparing changes in indices of inflammation, iron metabolism and erythropoiesis in aged C57BL/6 mice to aged mice with targeted deletions of interleukin-6 or hepcidin antimicrobial peptide. Circulating neutrophil and monocyte numbers and inflammatory cytokines increased with age. Decline in hemoglobin concentration and red blood cell number indicated that C57BL/6, interleukin-6 knockout mice, and hepcidin antimicrobial peptide knockout mice all demonstrated impaired erythropoiesis by 24 months. However, the interleukin-6 knock out genotype and the hepcidin antimicrobial peptide knock out genotype resulted in improved erythropoiesis in aged mice. Increased erythropoietic activity in the spleen suggested that the erythroid compartment was stressed in aged C57BL/6 mice compared to aged interleukin-6 knockout mice. Our data suggest C57BL/6 mice are an appropriate mammalian model for the study of anemia with age. Furthermore, although interleukin-6 and hepcidin antimicrobial peptide are not required, they can participate in the development of anemia in aging mice, and could be targeted, pre-clinically, with existing interventions to determine the feasibility of such agents for the treatment of anemia in older adults.

Background We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active.Design and Methods We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence.Results Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice.Conclusions Our results suggest that chronic inflammation inhibits late stages of erythroid production in the turpentine-induced sterile abscess model and induces features of impaired erythropoiesis which are distinct from those in hepcidin transgenic mice.

Although educational attainment has been consistently related to cognition in adulthood, the mechanisms are still unclear. Early education, and other social learning experiences, may provide the skills, knowledge, and interest to pursue intellectual challenges across the life course. Therefore, cognition in adulthood might reflect continued engagement with cognitively complex environments. Using baseline data from the Baltimore Experience Corps Trial, multiple mediation models were applied to examine the combined and unique contributions of intellectual, social, physical, creative, and passive lifestyle activities on the relationship between education and cognition. Separate models were tested for each cognitive outcome (i.e., reading ability, processing speed, memory). With the exception of memory tasks, findings suggest that education-cognition relations are partially explained by frequent participation in intellectual activities. The association between education and cognition was not completely eliminated, however, suggesting that other factors may drive these associations.