bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling Epigenetic Age in Single Cells
Authors: Trapp Alexandre , Kerepesi Csaba , Gladyshev Vadim 
Published: December 2021

Abstract
DNA methylation of a defined set of CpG dinucleotides emerged as a critical and precise biomarker of the aging process. Multi-variate machine learning models, known as epigenetic clocks, can exploit quantitative changes in the methylome to predict the age of bulk tissue with remarkable accuracy. However, intrinsic sparsity and digitized methylation in individual cells have so far precluded the assessment of aging in single cell data. We developed scAge, a probabilistic approach to determine the epigenetic age of single cells, and validated our results in mice. scAge tissue-specific and multi-cell type single cell clocks correctly recapitulated the chronological age of the original tissue, while uncovering the inherent heterogeneity that exists at the single-cell level. The data suggested that while cells in a tissue age in a coordinated fashion, some cells age more or less rapidly than others. We showed that individual embryonic stem cells exhibit an age close to zero, that certain stem cells in a tissue showed a reduced age compared to their chronological age, and that early embryogenesis is associated with the reduction of epigenetic age in individual cells, the latter supporting a natural rejuvenation event during gastrulation. scAge is both robust against the low coverage that is characteristic of single cell sequencing techniques and is flexible for studying any cell type and mammalian organism of interest. We demonstrate the potential for accurate epigenetic age profiling at single-cell resolution.
Genes Contributing to Resilience and Sensitivity to Lisinopril at Old Age: Clinical Translation of GWA in Drosophila
Authors: Gabrawy Mariann M , Khosravian Nick , Morcos George S , Jezek Meagan , Walston Jeremy , Abadir Peter M , Leips Jeff 
Published: December 2021

Abstract
Despite impressive results in restoring physical performance in rodent models, treatment with Renin-Angiotensin System (RAS) inhibitors such as Lisinopril have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs such as RAS inhibitors remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila, we tested the effects of Lisinopril on climbing speed and endurance at young and old age (N=14,310). Our data show that functional response and sensitivity to Lisinopril ranges from significant protection against physical decline (8–100% faster, P&lt; 0.0001) to increased weakness (P&lt; 0.0001) depending on both genotype and age (P&lt; 0.0001). Genome-wide analyses revealed little to no overlap in candidate polymorphisms influencing sensitivity between ages nor between treatments within each age. Furthermore, network analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in sensitivity to Lisinopril. Genetic knockdown of Axin, frizzled, nemo, and wingless, genes with human orthologs AXIN1, FZD1, NLK, and WNT1, respectively, abolished the effects of Lisinopril treatment. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and as potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age-dependent responses to pharmaceutical treatments.
Reduced Muscle Oxidative Capacity During and After Exercise in Older Adults With Obesity
Authors: Zhao Fei , Dutta Anirban , Tomita Machiko 
Published: December 2021

Abstract
Objective: Obesity and physical activity are two major factors affecting aerobic performance in older adults. The underlying mechanisms of the causes are still unknown. Oxidative capacity, muscles’ maximal capacity to utilize oxygen, is a part of aerobic performance. Muscle oxygen level (SmO2), a measure of oxidative capacity, reflects the balance between oxygen delivery and oxygen demand. When oxygen delivery surpasses oxygen demand, SmO2 increases, which indicates higher oxidative capacity. This study aimed to identify the influence of obesity and physical activity level on SmO2 changes during and after short exercise. Methods: This is a cross-sectional study. SmO2 changes during and after a bilateral heel-raise (BHR) test were measured in 60 community-dwelling older adults (≥ 60 years old) in four groups: inactive obese, active obese, inactive non-obese, and active non-obese. Inactive is defined as performing less than 150 minutes/week moderate-intensity activity. Results: The inactive obese group took a longer time for SmO2 drop during the BHR test, had a lower SmO2 level at the end, and recovered slower after the test than all other groups. Especially, compared with the active non-obese group, this group exhibited significantly poorer SmO2 recovery one minute after the test, 5.3% less (p=.036). The active obese group’s oxidative capacity was similar to the inactive non-obese group, although lower than the active non-obese group. Discussion: To prevent physical decline in older adults with obesity, regular exercise has been recommended. This study substantiated this from a hemodynamics viewpoint. Older adults with obesity need 150+ minutes/week moderate-intensity exercise.
Reducing Methylglyoxal Rescues Obesity Related Phenotypes and Lifespan in a Leptin Receptor Deficient Mouse Model
Authors: Wimer Lauren , Contreras Martin Valdearcos , Shanmugam Muniesh Muthaiyan , Ramirez Jessica , Beck Jennifer , Koliwad Suneil , Kapahi Pankaj 
Published: December 2021

Abstract
Obesity remains one of the leading risk factors for aging and age-related diseases such as Alzheimer’s and type II diabetes, and effects 40% of the US population. The occurrence of obesity has been closely tied to an increase in sugar consumption with chronic hyperglycemia enhancing glycolysis. One of the byproducts of glycolysis is methylglyoxal (MGO), a reactive precursor for advanced glycation end-products (AGEs), which drives type II diabetes and its complications. We hypothesize that an MGO-derived AGE, MG-H1, affects hypothalamic regulation of food consumption and metabolism parallel to the leptin pathway in mice fed a high carbohydrate diet. Exogenous supplementation of MG-H1 increased food consumption rates and weight gain. Conversely, glycation byproduct lowering compounds (GLY-LOW), a customized chemical cocktail that blocks the production of MGO, rescued over-feeding phenotypes in wild-type mice. Furthermore, GLY-LOW treatment in a leptin receptor deficient mouse model rescued weight gain, diabetic phenotypes and lifespan. RNA sequencing of the hypothalamus of leptin receptor deficient mice treated with GLY-LOW showed significant downregulation of Rax, a gene responsible for tanycyte differentiation, and several genes involved in feeding and aging. We propose that specific cells in the hypothalamus both make and respond to MG-H1. We will also discuss evidence for the potential of GLY-LOW as a new class of therapeutics that reduce the effects of glycation to reduce food intake and slow aging.
Targeting cellular senescence with novel senotherapeutics by design to extend healthspan
Authors: Zhang Lei , Hughes Brian , Angelini Luise , O’Kelly Ryan , Yousefzadeh Matthew , Kamenecka Ted , Niedernhofer Laura , Robbins Paul 
Published: December 2021

Abstract
Senescent cells accumulate with age in various tissues and organs, leading to the decline in tissue function and deterioration of many age-related diseases and aging. Senolytics have emerged as an effective therapeutic approach to eliminate senescent cells to improve aging phenotypes and associated co-morbidities. Despite their promising potential, only a handful of senolytics have been reported, including a natural flavonoid fisetin discovered by our group. Fisetin has been shown to reduce senescence, suppress age-related pathology, and extend healthspan in aged mice. However, its moderate potency, potential mutagenic risk and poor bioavailability have limited its further clinical applications. By leveraging drug design, medicinal chemistry and high-content imaging analysis, we have successfully optimized the senolytic activity of fisetin, leading to the identification of two improved fisetin senolytic analogs (FAs) with reduced toxicity in non-senescent cells. The improved senolytic activity of these FAs was demonstrated in murine and human senescent cell models as well as in accelerated aging and naturally aged mouse models. The analysis of the senolytic activity of the FAs as well as several other recently identified senolytics, including a senolytic lipid, will be presented.
The Interaction of Osmotic and Heavy Metal Stress in C. elegans
Authors: Turner Emily , Furtmann Amanda , Dang Hope , DeNicola Destiny , Sutphin George 
Published: December 2021

Abstract
Cellular stress is an ever-present aspect of aging and a primary driver of many common age-associated diseases such as cancer, diabetes, or neurodegenerative diseases. As we age, stress-induced damage accumulates over time, along with reduced efficacy of stress response pathways at combatting such damage. Molecular stress response pathways are well studied in the context of individual stressors, but there is a lack of understanding of how these responses change when multiple stressors are encountered at the same time. The goal of our work is to explore the impact of multiple simultaneous stressors on health and survival, and to investigate the underlying molecular pathways involved. To accomplish this, we utilize the nematode Caenorhabditis elegans to monitor lifespan changes in response to various stressors. We simultaneously exposed C. elegans to high concentrations of sodium chloride and cadmium chloride, known to induce osmotic and heavy metal stress, respectively. We found that lifespan is drastically decreased by the combined stress, significantly more so than the reduction in lifespan caused by either individual stress. Our results show that glycerol levels, which are normally increased in response to osmotic stress, are significantly lowered when the two stresses are combined compared to levels detected for osmotic stress alone. This suggests that the presence of cadmium may sensitize worms to sodium and other osmotic stressors by blunting cells’ ability to mount an appropriate molecular response. In ongoing work, we will continue to dissect the mechanisms through which cadmium influences glycerol production and other aspects of osmotic stress response.
Older Breast Cancer Survivors’ Cognitive Response to Qigong/Tai Chi Easy: An Exploratory Analysis
Authors: James Dara , Larkey Linda , Han SeungYong 
Published: December 2021

Abstract
Increasing rates of breast cancer coupled with improvements in treatment means the number of breast cancer survivors (BCSs) is growing. BCSs frequently report persistent cognitive deficits (i.e., “cancer-related cognitive impairment”) that impacts QOL and treatment compliance. Older (≥65 years old) BCSs are more likely to experience cognitive decline and impairment, partly due to the biological process of senescence. In the context of a larger RCT of BCSs (ages 45-75; stages 0-III), we evaluated cognitive function/performance effects on among the older participants (ages 65-75) of 8-weeks Qigong/Tai Chi Easy (QG/TCE) compared to education control (EdC). Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-COG), including: perceived cognitive impairment (PCI), and perceptions of effects of cognitive function on quality of life (PCQOL). Cognitive performance was measured using the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III): Digit Span (DS) and Letter-Number Sequencing (LNS). A multilevel model with random intercept was used to examine GroupXTime interactions: The majority of participants (N= 32) (M age= 69.7) were white (84%). Changes in WAIS-III DS, LNS and FACT-COG PCI were not statistically significant, but effect sizes were small to medium. The interaction between group and time was significant for FACT-COG PCQOL (p= 0.033) with a medium effect size, 0.14. Findings from this exploratory analysis of the larger study suggests that older BCSs’ participation in QG/TCE may improve perceptions of effects of cognitive function on quality of life. Such improvements may increase cognitive-related self-efficacy, overall QOL and treatment compliance among older BCSs.
Internalized age stereotypes as a mediator between volunteering and psychosocial health for adults 50+
Authors: Steward Andrew , Hasche Leslie , Laser-Maira Julie Anne 
Published: December 2021

Abstract
The productive aging literature describes a wide range of psychosocial benefits of volunteerism for older adults. A growing, compelling body of literature drawing from stereotype embodiment theory identifies significant, negative public health impacts of internalized age stereotypes. Yet, little research has explored which activities may reduce internalized ageism and enhance psychosocial health as people age. This cross-sectional study examined whether internalized age stereotypes mediate the relationship between volunteering and social connectedness for adults 50+. A convenience sample of volunteers (n = 112) 50+ years of age residing in the U.S. Mountain West were recruited. A 15-minute, online survey was utilized. The independent variable was number of volunteer hours per week (mean = 6.25, SD = 4.85). The dependent variable was social connectedness measured by five items positively worded from the five-point, Likert-type UCLA loneliness scale (α = .85; mean = 4.26, SD = 0.59). Drawing from the self-stereotypes of aging scale, the indirect effects of five internalized positive (e.g., “wise” and “capable”) and five negative (e.g., “grumpy” and “helpless”) age stereotypes were tested. Results indicate that increased internalized positive, not negative, age stereotypes partially mediated the relationship between volunteer hours and increased social connectedness, while holding constant age, gender, race, functional limitation, education, employment, length of volunteering, and previous volunteer experience. Although positive age stereotypes have long been considered a form of ageism, the results of this study suggest that internalizing positive age stereotypes may function as a form of esteem to promote enhanced psychosocial health as people age.
The relationship of Careers with People Interactions and Volunteering Between Gender-racial Groups in Late-life
Authors: Lai Patrick Ho Lam 
Published: December 2021

Abstract
Prior research showed that ethnic minorities in late-life tended to participate less in volunteering, compared to Whites. Older women, in general, spent more time volunteering than older men in the United States. Previous studies showed that occupational statuses, but have not yet discussed occupation categories, affected older adults' volunteering. The Current Population Survey dataset was utilized in this study to explore the relationship between careers with or without people interactions and volunteering of Americans aged 50 to 85 in an intersectionality lens. Regarding races, older African Americans who worked in occupations requiring human interactions, had almost double volunteering rate than those occupations not requiring these interactions. In respect of genders, compared to older men who worked in jobs requiring human interactions, the volunteer rate of those not requiring human interactions was 81% less. Either older African Americans or older men had more associations between their human interactions in career and their volunteering rate, than other racial groups or gender groups individually. Considering races and genders together, comparing to older Asian men who worked in fields needed interactions with others, the volunteering rate of those who did not work in these fields was 52% less. The association of older Asian men between fields requiring human interactions and volunteering rate was the least, among various gender-racial subgroups. Older adults with different racial-gender identities may face varying experiences in different types of occupations. Social and cultural factors among these identities are discussed to better understand the relationships between careers and volunteering in late-life.
Relationship Between Type 2 Diabetes Control and Cognition in Older Adults: Findings From NHANES
Authors: Jiwani Rozmin , Espinoza Sara , Wang Jing , Serra Monica 
Published: December 2021

Abstract
Cognitive health has emerged as an important public health concern for America’s aging population. Type 2 Diabetes (T2D) may be associated with an exacerbated decline in cognitive performance. This study aimed to examine the relationship between T2D control and cognitive performance in older adults (≥60 years) using the 2013-2014 National Health and Nutrition Examination Surveys. Participants who completed the following cognitive assessments were included: 1) Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL), 2) Animal Fluency (AF), 3) Digit Symbol Substitution Test (DSST) (higher scores associated with better cognition). Participants were stratified by four groups: no T2D (N=557), treated/controlled T2D (controlled; N=41), treated/uncontrolled T2D (uncontrolled; N=120), untreated T2D (N=86), based on self-reported T2D treatment, fasting plasma glucose, and hemoglobin A1c. Logistic regression was used to examine the relationship between T2D control and cognition. We observed that those with uncontrolled and untreated T2D each had ~15% lower DSST than those with no T2D (P&lt;0.01). CERAD-WL and AF were similar across all groups. Unadjusted analyses showed that individuals with 1) lower CERAD-WL were more likely to have controlled and untreated T2D, 2) lower AF were more likely to have controlled and uncontrolled T2D, and 3) lower DSST were more likely to have uncontrolled and untreated T2D (P’s&lt;0.05). After adjusting for significant demographics and cardiovascular risk factors, only having uncontrolled T2D was associated with lower DSST (β=-3.164, P=0.04). These data indicate the need for longitudinal studies to further explore dynamic relationship and causal pathway between T2D control and cognitive impairment.
Risk factors for dementia onset in older adults with metastatic renal cell carcinoma
Authors: Miller Samuel , Wilson Lauren , Greiner Melissa , Pritchard Jessica , Zhang Tian , Kaye Deborah , Cohen Harvey , Dinan Michaela 
Published: December 2021

Abstract
Renal dysfunction is a driver of dementia. It is also associated with renal cell carcinoma, possibly the result of the tumor itself or from cancer treatment. This study evaluates metastatic renal cell carcinoma (mRCC) as a risk factor for developing mild cognitive impairment or dementia (MCI/D) as well as the impact of RCC-directed therapies on the development of MCI/D. We identified all patients diagnosed with mRCC in SEER-Medicare from 2007-2015. The main outcome was incident MCI/D within one year of mRCC diagnosis or cohort entry. Exclusion criteria included age &lt;65 at mRCC diagnosis and diagnosis of MCI/D within preceding year of mRCC diagnosis. Patients with mRCC (n=2,533) were matched to non-cancer controls (n=7,027) on age, sex, race, comorbidities and year. Cox proportional hazards regression showed that having mRCC (HR 8.52, 95% MCI/D 6.49-11.18, p&lt;0.001) and being older (HR 1.05 for 1-year age increase, 95% MCI/D 1.03-1.07, p&lt;0.001) were predictive of developing MCI/D. A second Cox proportional hazards regression of only patients with mRCC revealed that neither those initiating treatment with oral anticancer agents (OAAs) nor those who underwent nephrectomy were more likely to develop MCI/D. Black patients had a higher risk of dementia compared to white patients (HR 1.92, 95% MCI/D 1.02-3.59, p=0.047). In conclusion, patients with mRCC were more likely to develop MCI/D than those without mRCC. The medical and surgical therapies evaluated were not associated with increased incidence of MCI/D. The increased incidence of MCI/D in older adults with mRCC may be the result of the pathology itself.
Does HbA1c Influence the Relationship between Stress and Cognition? Findings from the VA Normative Aging Study
Authors: Brockmann Austin , Aldwin Carolyn , Spiro Avron 
Published: December 2021

Abstract
Type 2 diabetes has increased in prevalence globally, with potential adverse effects on cognition. Both high levels of hemoglobin A1c (HbA1c) and stressful life events (SLEs) are associated with impaired cognitive performance, but few studies have examined their synergistic effects. The present study examined direct effects of stress and HbA1c on several cognitive outcomes, and whether HbA1c moderated the relationship between SLEs and cognition. Utilizing a sample of 527 older men from the VA Normative Aging Study (Mage = 74.3, SD = 6.5), stress was inversely related to MMSE, verbal fluency, and pattern recognition; HbA1c was only inversely associated with MMSE. The moderation model was supported only for pattern recognition (β = 1.64, p &lt; .05), with stress having worse effects in those high in HbA1c. Stratifying analyses by age group (&lt;75, 75+) showed that stress predicted cognition only in the young-old, while HbA1c was inversely related to cognition only in old-old participants. Further, these age-group analyses yielded different effects of demographics on cognition. In the young-old, age was consistently inversely related to all cognitive outcomes, but in the old-old only with MMSE and word list recall. Among the young-old, education was associated with only word list recall but improved performance for most scales among the old-old. Finally, HbA1c intensified the effect of stress moderation on verbal fluency only in old-old (β = 2.78, p &lt; .05). In summary, stress was more important for cognition in the young-old, while education and health status were more important in the old-old.
Effects of Age and Self-Performance on Memory for the Actions of Other People
Authors: Kersten Alan , Earles Julie , Brymer Jennifer 
Published: December 2021

Abstract
This research tested whether performing an action themselves leads young and older adults to have difficulty remembering which of a number of other people had performed that same action. It also tested whether observing another person perform an action leads to false memory for self-performance of that action. Young adults and healthy older adults 62 to 88 years of age viewed videos of actors performing actions. After viewing some of the actions, participants were instructed to perform those same actions themselves. Participants were tested one week later on their memory for their own actions and for the actions of the actors in the videos. Older adults were more strongly influenced by self-performance than were young adults when asked whether the actor in a test item had performed the same action previously. Young adults performed better than older adults at discriminating the correct and incorrect actors in the videos, although both groups showed reduced discrimination for actions that they had also performed themselves. The two groups were equally likely to falsely remember having performed an action that had only appeared in the videos, but young adults were better able than older adults to correctly identify the actions that they had in fact performed. Older adults thus have greater difficulty than young adults at distinguishing self-performed actions from actions performed by other people. This suggests the existence of common representations for the actions of oneself and others that must be bound to identity information to specify the correct source of the actions.