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Eileen M Crimmins

Publications and source records attributed to Eileen M Crimmins.

15 recordsLinked to original sources
PubMed2026

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin↗
PubMed2026

An immune-associated mitochondrial DNA variant with sex differences reveals a putative novel microprotein called MASL.

The use of mitochondrial wide association studies (MiWAS) to link mitochondrial DNA variants (mtSNPs) to phenotypes of interest has uncovered important connections between mitochondrial genes and human health. The recent introduction of a re-annotated mitochondrial genome that accounts for small open reading frames (sORFs) with protein coding potential suggests the existence of mitochondrial-derived microproteins, many of which remain uncharacterized. Thus, considering the re-annotated mitochondrial genome when conducting genomic analyses such as MiWAS facilitates the mapping of mtSNPs back to microprotein-encoding sORFs and uncovers interactions between mitochondrial microproteins and biological systems. Here, we employ MiWAS of venous blood samples from the Health and Retirement Study (HRS) and identify a mtSNP associated with sex-specific changes to immune composition. After accounting for re-annotation, we map the identified mtSNP back to a sORF that encodes a novel microprotein, termed MASL (Mitochondrial Associated Small d-Loop peptide). Complementary phenome-wide association studies (PheWAS) in HRS and and UK Biobank confirm interactions between this mtSNP and immune phenotypes of interest, and our targeted RNA-Seq method (mitoSNP-seq) elucidates sex-differences in gene expression and functional pathways potentially altered by this mtSNP that may be relevant to the associated microprotein. Early characterization of the MASL microprotein shows sex-differences in circulating MASL levels in human plasma, and sex-specific interactions when comparing male and female mice treated with synthesized MASL. Together, the results of this study not only contribute to our understanding of mitochondrial dynamics in immunity, but also provide early characterization of a novel mitochondrial-derived microprotein with sex-specific modulatory effects.

Genomics↗
PubMed2006

Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E 4 alleles: MacArthur studies of successful aging.

BACKGROUND: Growing evidence from animal studies suggests an interaction between antioxidants and apolipoprotein E (APOE) alleles on cognitive functioning. We used data from a 7-year cohort study of high-functioning older persons to explore whether the associations between serum beta-carotene level and subsequent decline of cognitive function differed by APOE 4 genotype. METHODS: Baseline information on sociodemographic characteristics, serum beta-carotene level, inflammation markers, APOE genotype, and cognitive functioning measured by a 9-item Short Portable Mental Status Questionnaire (SPMSQ) was obtained in 455 survivors. Multivariable logistic regression analyses were used to examine the relation between high serum beta-carotene level and risk of SPMSQ score decline in participants with or without APOE 4 alleles, while adjusting for age, sex, race, baseline SPMSQ score, and other covariates. RESULTS: Nine (2%) study participants had homozygous and 97 (21%) had heterozygous APOE 4 alleles. Two hundred forty-nine (55%) had decline of SPMSQ scores during the follow-up. The presence of an APOE 4 allele was associated with higher risk and larger magnitude of SPMSQ score decline. The adjusted odds ratio of high beta-carotene level for cognitive decline was 0.11 (95% confidence interval, 0.02-0.57) in participants with at least one APOE 4 allele and 0.89 (95% confidence interval, 0.54-1.47) among those who were APOE 4 negative. CONCLUSION: Among high-functioning older persons, antioxidants and beta-carotene in particular may offer protection from cognitive decline in persons with greater genetic susceptibility as evidenced by the presence of the APOE 4 allele.

Activities of Daily Living↗
PubMed2005

Infection, inflammation, height, and longevity.

Using historical data from cohorts born before the 20th century in four northern European countries, we show that increasing longevity and declining mortality in the elderly occurred among the same birth cohorts that experienced a reduction in mortality at younger ages. Concurrently, these cohorts also experienced increasing adult height. We hypothesize that both the decline in old-age mortality and the increase in height were promoted by the reduced burden of infections and inflammation. Thus, early growth and cardiovascular diseases of old age may share infectious and inflammatory causes rooted in the external environment.

Adolescent↗
PubMed2005

Socioeconomic status and C-reactive protein levels in the US population: NHANES IV.

C-reactive protein (CRP), a marker of inflammation, has been identified as a risk factor for cardiovascular disease and mortality. Using data on adults aged 20 and over from the fourth National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey, we examined the association between socioeconomic status and CRP in US adults (N=7634). Socioeconomic variation in CRP occurred only at very high levels of CRP (>10.0 mg/L). There was no significant difference in the prevalence of moderate (1.1-3.0 mg/L) or high values of CRP (3.1-10.0mg/L) by socioeconomic status; however, among those with family income at or below the poverty level, 15.7% had very high levels of CRP (greater than 10.0 mg/L), compared to only 9.1% of those in families above the poverty level. Logistic regression results indicate that acute illness, chronic conditions, and differential health behaviors account for about two-thirds of this association. African Americans, Hispanics, and women were more likely to have high levels of CRP. Obesity was the largest risk factor for every level of CRP above normal. Results suggest that differences in very high CRP may be due to factors beyond acute illness and may also reflect chronic health, behavioral and disease processes associated with low socioeconomic status.

Adult↗
PubMed2005

Changes in biological markers of health: older Americans in the 1990s.

BACKGROUND: Many studies that show improved health in older adults have relied on subjective measures of health. This article assesses changes in the physiological status of older Americans during the 1990s using biological measures of high-risk for morbidity and mortality. METHODS: Changes in the prevalence of clinically-defined, high risk for 10 biological markers were assessed in respondents age 65 years and older from National Health and Nutrition Examination Surveys (NHANES) III (1988-1994) and IV (1999-2000). RESULTS: Some changes in prevalence of high-risk values of biological markers indicate improved health among older adults in the 1990s: a 6% reduction in the prevalence of high-risk total cholesterol (p <.001) and a 7% reduction in the prevalence of high-risk homocysteine (p <.001). Other changes indicate worsening health: a 9% increase in the prevalence of high-risk systolic blood pressure (p <.01), a 10% increase in obesity (p <.001), and an 8% increase in the prevalence of high-risk C-reactive protein (p <.001). These changes remained significant after adjusting for age, sex, and education. Results of logistic regressions indicate that changes in the frequency of medication usage, medication efficacy, prevalence of chronic disease, and diet explained some of these changes. CONCLUSIONS: Changes in the prevalence of high-risk values of biological markers in the 1990s are mixed. Greater use and effectiveness of lipid-lowering medication has contributed to the reduction in percentage of the population with high-risk lipid levels, and folate supplementation accounted for a decline in the percentage with high-risk homocysteine. However, increases in the percentage with high-risk systolic blood pressure occurred despite an increase in the use of antihypertensive medications, in part because of the limited ability of antihypertensive medications to bring blood pressure below high-risk levels.

Aged↗
PubMed2005

The impact of obesity on active life expectancy in older American men and women.

PURPOSE: The purpose of this article is to estimate the effect of obesity on both the length of life and length of nondisabled life for older Americans. DESIGN AND METHODS: Using data from the first 3 waves of the Asset and Health Dynamics Among the Oldest Old (AHEAD) survey, this article develops estimates of total, active, and disabled life expectancy for obese and nonobese older men and women. We used the Interpolation of Markov Chains (IMaCh) method to estimate the average number of years obese and nonobese older persons can expect to live with and without activity of daily living (ADL) disability. RESULTS: Our findings indicate that obesity has little effect on life expectancy in adults aged 70 years and older. However, the obese are more likely to become disabled. This means that obese older adults live both more years and a higher proportion of their remaining lives disabled. IMPLICATIONS: The lack of significant differences in life expectancy by obesity status among the old suggests that obesity-related death is less of a concern than disability in this age range. Given steady increases in obesity among Americans at all ages, future disability rates may be higher than anticipated among older U.S. adults. In order to reduce disability among future cohorts of older adults, more research is needed on the causes and treatment of obesity and evaluations done on interventions to accomplish and maintain weight loss.

Activities of Daily Living↗
PubMed2004

Inflammatory exposure and historical changes in human life-spans.

Most explanations of the increase in life expectancy at older ages over history emphasize the importance of medical and public health factors of a particular historical period. We propose that the reduction in lifetime exposure to infectious diseases and other sources of inflammation--a cohort mechanism--has also made an important contribution to the historical decline in old-age mortality. Analysis of birth cohorts across the life-span since 1751 in Sweden reveals strong associations between early-age mortality and subsequent mortality in the same cohorts. We propose that a "cohort morbidity phenotype" represents inflammatory processes that persist from early age into adult life.

Adult↗
PubMed2004

Workplace characteristics and work disability onset for men and women.

OBJECTIVES: This paper investigates the association between job characteristics and work disability among men and women in older working ages in the United States. We examine whether the association persists when controlling for major chronic disease experience. We also address whether job characteristics are ultimately associated with the receipt of disability benefits. METHODS: Data are from the Health and Retirement Survey and are nationally representative of noninstitutionalized persons 51-61 in 1992. Disability onset is estimated using a hazard modeling approach for those working at wave 1 (N = 5,999). A logistic regression analysis of disability benefits is based on a risk set of 525 persons who become work-disabled before the second interview. RESULTS: Women's disability onset and health problems appear less related to job characteristics than men's. For men, work disability is associated with stressful jobs, lack of job control, and environmentally hazardous conditions but is not associated with physical demands. Participation in disability benefit programs among those with work disability is unrelated to most job characteristics or health conditions. CONCLUSIONS: Understanding of the differing process to work disability for men and women and the relationship between work and health by gender is important for current policy development.

Persons with Disabilities↗
PubMed2004

The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging.

BACKGROUND: It remains unclear to what extent the associations between low serum beta-carotene concentration and increased risk for cardiovascular disease and cancers are attributable to inflammation. The objective of this study was to evaluate simultaneously the effects of serum beta-carotene concentration and inflammation on the subsequent all-cause mortality risk in high-functioning older persons. METHODS: The authors conducted a prospective cohort study using information from 672 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum concentrations of beta-carotene, C-reactive protein, interleukin-6, cholesterols, and albumin; body mass index; waist:hip ratio; prevalent medical conditions; health behaviors; and medications. Sex-specific univariate and multivariate logistic regression analyses were used to study the effects of low beta-carotene, high inflammation burden, or both on 7-year all-cause mortality rates while adjusting for other confounders. RESULTS: The serum beta-carotene concentration was inversely associated with C-reactive protein and interleukin-6 levels. After adjustment for inflammation markers and other covariates, the relative risks for low beta-carotene for the 7-year all-cause mortality risk were 2.30 (95% confidence interval [CI], 1.23 to 4.31) in men and 0.85 (95% CI, 0.42 to 1.75) in women. Compared with men with high beta-carotene levels and low inflammation, the multiply adjusted relative risk for low beta-carotene and high inflammation burden was 3.78 (95% CI, 1.69 to 8.47) in men. CONCLUSIONS: Low levels of serum beta-carotene are independently associated with an increased all-cause mortality risk in older men, even after adjustment for the effects of inflammation and other risk factors. In men, but not women, a synergistic effect occurs between low beta-carotene concentration and high inflammation burden in predicting higher mortality rates.

Aged↗
PubMed2004

Trends in the health of the elderly.

Health among the older population as measured by most dimensions has improved during the last two decades. Mortality has continued to decline, and disability and functioning loss are less common now than in the past. However, the prevalence of most diseases has increased in the older population as people survive longer with disease, and the reduction in incidence does not counter the effect of increased survival. On the other hand, having a disease appears to be less disabling than in the past.

Aged↗
PubMed2003

Age differences in allostatic load: an index of physiological dysregulation.

This preliminary report examines variation in allostatic load by age for a large nationally representative population of the United States. It uses data on 13 indicators of physiologic dysregulation from a nationally representative sample of the US population 20 years of age and over. Allostatic load is remarkably constant in the older ages after increasing sharply in the years from 20 to 60. We hypothesize that this represents mortality selectivity of the population by physiological status.

Adaptation, Physiological↗
PubMed2002

The relationship between cognitive and physical performance: MacArthur Studies of Successful Aging.

BACKGROUND: The relationship between change in cognitive and physical performance has yet to be fully understood. Because aging decreases the ability to learn new information while preserving more established knowledge, this article examines whether the association between change in cognitive and physical performance depends on the nature of the physical task. METHODS: Data from the MacArthur Research Network on Successful Aging Community Study--a longitudinal three-site, cohort study of high-functioning, disability-free Americans aged 70 to 79 in 1988 (reinterviewed in 1991 and 1995)--are used for this investigation. We examine the association between change in cognitive performance and two categories of physical performance: novel/attentional demanding physical tasks (e.g., standing on a single leg) or routine physical tasks (e.g., walking at a normal pace). Change in physical performance (over 7 years) is regressed on change in cognitive performance (over the same period) controlling for baseline cognitive ability, demographic factors, health status, and behavioral characteristics. RESULTS: The findings suggest that declines in cognitive performance are associated with declines in both novel/attentional demanding and routine physical tasks. In addition to decline in cognition, gender, prevalent health conditions (e.g., cancer, high blood pressure, and the fracture of a hip), and smoking behavior are associated with decline in performance on some physical tasks. CONCLUSIONS: The findings suggest that the successful execution of physical tasks demands cognitive processes regardless of the nature of the task. Researchers using performance-based measures of physical functioning should pay particular attention to the cognitive capacities of their subjects and how these might influence their assessment.

Aged↗
PubMed2002

Life with and without disease: women experience more of both.

This paper examines gender differences in life with and without six major diseases, including both mortal and morbid conditions. Disease prevalence and health behavior data are from the 1993-1995 National Health Interview Surveys for the United States. Vital registration data are the source of mortality rates used in computing life expectancy. The Sullivan method is used to estimate life lived with and without disease and risky behavior for men and women at various ages. Women live more years with each of the diseases examined, and, for arthritis, the extended years with disease are greatest. Women also live more years than men free of each of these diseases with the exception of arthritis. Gender differences in life without two health-risk behaviors are also discussed. Men spend more years of their lives overweight and have fewer years during which they see a doctor.

Adolescent↗