Annelise A Madison, Christin E Burd, Rebecca Andridge, Stephanie J Wilson, Michael T Bailey, Martha Belury, Daniel J Spakowicz, William Malarkey, Janice K Kiecolt-Glaser
Background This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan. Methods Peripheral blood was obtained from 96 study participants (N=96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation. T cell aging mRNA markers were combined into an aging index and the Horvath epigenetic clock algorithm was used to calculate epigenetic age based on DNA methylation status of over 500 loci. Participants also collected a stool sample from which the V4 region of the 16S rRNA gene was sequenced to derive the Shannon and Simpson diversity indices, and the total count of observed operational taxonomic units (richness). Models controlled for BMI, comorbidities, sex, dietary quality, smoking status, physical activity, and sleep quality. Results Lower microbiota richness was associated with higher T cell age based on mRNA markers, but when probing the region of significance, this relationship was only significant among adults 45 years and older (p=.03). Lower Shannon diversity (p=.05) and richness (p=.07) marginally correlated with higher epigenetic age (i.e., greater T cell DNA methylation). Conclusion Gut microbiota complexity may correspond with the rate of T cell aging, especially in mid-to-late life. These results suggest an interplay between the gut microbiome and immunological aging that warrants further experimental work.
研究背景 本研究探讨了肠道微生物群的多样性和丰富度与 96 名各年龄段健康成年人的 T 细胞衰老之间的关系。研究还探讨了这些联系在整个生命周期中是否存在差异。方法 采集 96 名研究参与者（N=96，年龄 21-72 岁）的外周血，评估 T 细胞衰老的 mRNA 标记（p16ink4a、p14ARF、B3gat1、Klrg1）和 DNA 甲基化。T 细胞衰老 mRNA 标记被合并成一个衰老指数，Horvath 表观遗传时钟算法则根据 500 多个位点的 DNA 甲基化状态计算表观遗传年龄。参与者还采集了粪便样本，并对其中的 16S rRNA 基因 V4 区域进行了测序，以得出香农和辛普森多样性指数以及观察到的操作分类单位总数（丰富度）。模型对体重指数、合并症、性别、饮食质量、吸烟状况、体力活动和睡眠质量进行了控制。结果 根据 mRNA 标记，较低的微生物群丰富度与较高的 T 细胞年龄相关，但在探究显著性区域时，这种关系仅在 45 岁及以上的成年人中显著（p=.03）。较低的香农多样性（p=.05）和丰富度（p=.07）与较高的表观遗传年龄（即较高的 T 细胞 DNA 甲基化）略有关联。结论 肠道微生物群的复杂性可能与 T 细胞的衰老速度相对应，尤其是在中晚期。这些结果表明，肠道微生物群与免疫学衰老之间存在相互作用，值得进一步开展实验研究。
{"title":"Gut Microbiota Richness and Diversity Track with T Cell Aging in Healthy Adults","authors":"Annelise A Madison, Christin E Burd, Rebecca Andridge, Stephanie J Wilson, Michael T Bailey, Martha Belury, Daniel J Spakowicz, William Malarkey, Janice K Kiecolt-Glaser","doi":"10.1093/gerona/glad276","DOIUrl":"https://doi.org/10.1093/gerona/glad276","url":null,"abstract":"Background This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan. Methods Peripheral blood was obtained from 96 study participants (N=96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation. T cell aging mRNA markers were combined into an aging index and the Horvath epigenetic clock algorithm was used to calculate epigenetic age based on DNA methylation status of over 500 loci. Participants also collected a stool sample from which the V4 region of the 16S rRNA gene was sequenced to derive the Shannon and Simpson diversity indices, and the total count of observed operational taxonomic units (richness). Models controlled for BMI, comorbidities, sex, dietary quality, smoking status, physical activity, and sleep quality. Results Lower microbiota richness was associated with higher T cell age based on mRNA markers, but when probing the region of significance, this relationship was only significant among adults 45 years and older (p=.03). Lower Shannon diversity (p=.05) and richness (p=.07) marginally correlated with higher epigenetic age (i.e., greater T cell DNA methylation). Conclusion Gut microbiota complexity may correspond with the rate of T cell aging, especially in mid-to-late life. These results suggest an interplay between the gut microbiome and immunological aging that warrants further experimental work.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138822706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erica Twardzik, Jennifer A Schrack, Vicki A Freedman, Nicholas S Reed, Joshua R Ehrlich, Pablo Martinez-Amezcua
Background Appropriate conceptualization and measurement of disability are critical for population-focused resource allocation and policy development. Self-reported and performance-based measures of functioning have been used to represent disability. Variation in environmental context or self-perception of ability may influence self-reports; however, performance-based measures that attempt to control environmental context may not accurately capture real-world aspects of functioning. This study examined the agreement between self-report and performance-based measures of functioning within four domains among older adults. Methods Cross-sectional data from the 2021 National Health and Aging Trends Study was used. Self-reported and performance-based measures of functioning were assessed for vision, hearing, mobility, and memory domains. We examined the diagnostic characteristics of performance-based vs. self-reported measures using sensitivity, specificity, and receiver operating characteristics curves. Differences in the agreement of these measures across sociodemographic groups was investigated using logistic regression. Results Among 2,442 respondents 71 years and older (mean 78.5 ±5.3, 56% female), performance measures of hearing and mobility had high sensitivity (89% and 91%, respectively) and low/moderate specificity (36% and 63%, respectively). The sensitivity and specificity of vision measures were 71%. Memory measures had high specificity (89%) and low sensitivity (28%). Performance-based discrimination ranged from 0.59 (memory) to 0.78 (mobility). Agreement varied across sociodemographic factors. Conclusions Performance measures diverge from self-reported functioning among older adults. Discordance may reveal opportunities for environmental intervention where participants' performance does not capture the full extent of barriers in the daily lives. Additional research is needed to investigate individual and environmental factors which could explain the observed differences.
{"title":"An Incomplete Model of Disability: Discrepancies Between Performance-Based and Self-Reported Measures of Functioning","authors":"Erica Twardzik, Jennifer A Schrack, Vicki A Freedman, Nicholas S Reed, Joshua R Ehrlich, Pablo Martinez-Amezcua","doi":"10.1093/gerona/glad271","DOIUrl":"https://doi.org/10.1093/gerona/glad271","url":null,"abstract":"Background Appropriate conceptualization and measurement of disability are critical for population-focused resource allocation and policy development. Self-reported and performance-based measures of functioning have been used to represent disability. Variation in environmental context or self-perception of ability may influence self-reports; however, performance-based measures that attempt to control environmental context may not accurately capture real-world aspects of functioning. This study examined the agreement between self-report and performance-based measures of functioning within four domains among older adults. Methods Cross-sectional data from the 2021 National Health and Aging Trends Study was used. Self-reported and performance-based measures of functioning were assessed for vision, hearing, mobility, and memory domains. We examined the diagnostic characteristics of performance-based vs. self-reported measures using sensitivity, specificity, and receiver operating characteristics curves. Differences in the agreement of these measures across sociodemographic groups was investigated using logistic regression. Results Among 2,442 respondents 71 years and older (mean 78.5 ±5.3, 56% female), performance measures of hearing and mobility had high sensitivity (89% and 91%, respectively) and low/moderate specificity (36% and 63%, respectively). The sensitivity and specificity of vision measures were 71%. Memory measures had high specificity (89%) and low sensitivity (28%). Performance-based discrimination ranged from 0.59 (memory) to 0.78 (mobility). Agreement varied across sociodemographic factors. Conclusions Performance measures diverge from self-reported functioning among older adults. Discordance may reveal opportunities for environmental intervention where participants' performance does not capture the full extent of barriers in the daily lives. Additional research is needed to investigate individual and environmental factors which could explain the observed differences.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"252 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background This study examined the relation between declines in physical and cognitive performance in older people. Method A population-based cohort of 7483 adults (average age 72 years) were interviewed. Physical performance was assessed with three standardized tests and a combination of four cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using change in the predictor measured one, two or three intervals before the outcome change. Results Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the one-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together. Conclusion Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions.
{"title":"Temporal Patterns of Change in Physical and Cognitive Performance","authors":"Pankaja Desai, Shannon Halloway, Kristin Krueger, Kumar B Rajan, Denis Evans","doi":"10.1093/gerona/glad274","DOIUrl":"https://doi.org/10.1093/gerona/glad274","url":null,"abstract":"Background This study examined the relation between declines in physical and cognitive performance in older people. Method A population-based cohort of 7483 adults (average age 72 years) were interviewed. Physical performance was assessed with three standardized tests and a combination of four cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using change in the predictor measured one, two or three intervals before the outcome change. Results Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the one-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together. Conclusion Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"176 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138564983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sydney T Thai, Jennifer L Lund, Kelly M Kenzik, Charles Poole, Til Stürmer, John B Buse, Christian A Harmon, Mustafa Al-Obaidi, Grant R Williams
Background Many older adults with cancer have ≥2 impairments on geriatric assessment which impacts present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality. Methods We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences, hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, pre-frail, frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, esophageal) vs. low-risk gastrointestinal cancers, and stage (IV vs. I-III). Results Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50% and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1 Conclusions The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions.
{"title":"Geriatric Assessment Impairment Profiles and Mortality in Older Adults with Gastrointestinal Cancers: Latent Class Analysis of the CARE Registry","authors":"Sydney T Thai, Jennifer L Lund, Kelly M Kenzik, Charles Poole, Til Stürmer, John B Buse, Christian A Harmon, Mustafa Al-Obaidi, Grant R Williams","doi":"10.1093/gerona/glad273","DOIUrl":"https://doi.org/10.1093/gerona/glad273","url":null,"abstract":"Background Many older adults with cancer have ≥2 impairments on geriatric assessment which impacts present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality. Methods We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences, hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, pre-frail, frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, esophageal) vs. low-risk gastrointestinal cancers, and stage (IV vs. I-III). Results Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50% and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1 Conclusions The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138559186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] =1.34, 95% confidence interval [CI] =1.06 to 1.69, p=0.015) and VD (HR=1.61, 95% CI=1.21 to 2.13, p=0.001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (β= -95.25 mm3, 95% CI= -165.31 to -25.19 mm3, p=0.014) and amygdala (β= -51.85 mm3, 95% CI= -88.02 to -15.68 mm3, p=0.012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p>0.05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.
{"title":"Associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure: evidence from 466,224 UK Biobank participants","authors":"Yitong Ling, Shiqi Yuan, Xiaxuan Huang, Shanyuan Tan, Hongtao Cheng, Anding Xu, Jun Lyu","doi":"10.1093/gerona/glad266","DOIUrl":"https://doi.org/10.1093/gerona/glad266","url":null,"abstract":"Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] =1.34, 95% confidence interval [CI] =1.06 to 1.69, p=0.015) and VD (HR=1.61, 95% CI=1.21 to 2.13, p=0.001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (β= -95.25 mm3, 95% CI= -165.31 to -25.19 mm3, p=0.014) and amygdala (β= -51.85 mm3, 95% CI= -88.02 to -15.68 mm3, p=0.012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p>0.05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"103 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138455372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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