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Early life circumstances and their impact on health in adulthood and later life: a systematic review

3 weeks 4 days ago
INTRODUCTION: Certain situations and contexts during early years of life and childhood can have a significant impact on the health of older individuals. Studies have demonstrated that adversities such as poverty, neglect, abuse, and exposure to chronic stress conditions during the early years of life are associated with a range of health problems in adulthood.
Weslley Barbosa Sales

Tlr7 drives sex differences in age- and Alzheimer's disease-related demyelination

3 weeks 4 days ago
Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened...
Chloe Lopez-Lee

A panoramic view of cell population dynamics in mammalian aging

3 weeks 4 days ago
To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, sexes, and genotypes. This comprehensive dataset reveals more than 3,000 unique cellular states and over 200 aging-associated cell populations. Our panoramic analysis uncovered organ-, lineage-, and sex-specific shifts of cellular dynamics during lifespan progression. Moreover, we identify both...
Zehao Zhang

<em>Tlr7</em> drives sex differences in age- and Alzheimer's disease-related demyelination

3 weeks 4 days ago
Alzheimer's disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened...
Chloe Lopez-Lee

Overlooked histories in ageing research: Pioneering women at the foundation of our field

3 weeks 4 days ago
A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer 'history of the field' that many of us present in our classrooms, conference halls and writings often tends to be dominated by men. Although numerous men have made...
Marina Ezcurra

Accelerating the pace of elder justice policy to meet the needs of a growing aging population

3 weeks 4 days ago
Policy measures designed to address elder abuse, neglect, and exploitation date back to decades, including the Older Americans Act of 1965. Over the years, various legislative actions have aimed to address elder mistreatment, culminating in the Elder Justice Act of 2010. Despite these efforts, policy changes lag behind need, and government funding appropriation is woefully inadequate. On November 29, 2023, the National Collaboratory to Address Elder Mistreatment convened 76 experts from...
Kristin Lees Haggerty

Telomerase RNA component knockout exacerbates <em>Staphylococcus aureus</em> pneumonia by extensive inflammation and dysfunction of T cells

3 weeks 4 days ago
The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation. Our study unveils heightened susceptibility to pneumonia caused by Staphylococcus aureus (S. aureus) in Terc knockout (Terc^(ko/ko)) mice compared to both young and old infected counterparts. The exacerbated infection in Terc^(ko/ko) mice correlates with heightened inflammation, manifested by elevated interleukin-1β...
Yasmina Reisser

Study design features increase replicability in brain-wide association studies

3 weeks 4 days ago
Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behaviour associations^(1,2). Several recent studies have shown that thousands of study participants are required for good replicability of BWAS^(1-3). Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium⁴ (77,695 total scans) to demonstrate that optimizing study design is critical for increasing...
Kaidi Kang

The Ercc1<sup>-/Δ</sup> mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration

3 weeks 4 days ago
Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related...
Akilavalli Narasimhan

Multimorbidity is associated with myocardial DNA damage, nucleolar stress, dysregulated energy metabolism, and senescence in cardiovascular disease

3 weeks 4 days ago
This study investigates why individuals with multimorbidity-two or more chronic conditions-are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating...
Kristina Tomkova

Rab8a restores diverse innate functions in CD11c<sup>+</sup>CD11b<sup>+</sup> dendritic cells from aged mice

3 weeks 4 days ago
Age-related alterations of the immune system compromise the host's ability to respond to pathogens, but how immune aging is regulated is still poorly understood. Here, we identify via transcriptomic analysis of splenic DCs and bone marrow derived dendritic cells (BMDC) of young and aged mice, the small GTPase Rab8a as a regulator of dendritic cell (DC) functions in mice. CD11c^(+)CD11b^(+) DCs of aged in comparison to young host exhibit a diminished type I IFN response upon viral stimulation and...
Sudhakar Singh

Sex differences in skeletal muscle metabolism in exercise and type 2 diabetes mellitus

3 weeks 4 days ago
This Review focuses on currently available literature describing sex differences in skeletal muscle metabolism in humans, as well as highlighting current research gaps within the field. These discussions serve as a call for action to address the current lack of sufficient sex-balanced studies in skeletal muscle research, and the resulting limitations in understanding sex-specific physiological and pathophysiological responses. Although the participation of women in studies has increased, parity...
Kirstin MacGregor

Advancing prediction of age-related vascular cognitive impairment based on peripheral and retinal vascular health in a pilot study: a novel comprehensive assessment developed for a prospective workplace-based cohort (The Semmelweis Study)

3 weeks 4 days ago
With a growing elderly population in the European Union, age-related diseases associated with unhealthy aging pose increasing public health challenges, including a loss of independence and heightened societal burdens. The Semmelweis Study, a prospective occupational cohort study in Hungary, seeks to identify determinants of unhealthy aging, focusing on the complex relationship between lifestyle, environmental, occupational factors, and the development of chronic age-associated diseases,...
Tamas Csipo

Dysregulation of astrocytic Aquaporin-1 in the brains of oldest-old rhesus macaques: the NIA caloric restriction study

3 weeks 4 days ago
Aquaporin-1 (AQP1) is a highly conserved water-channel protein, found to be expressed by astrocytes in adult humans and non-human primates (NHPs). Upregulation of cortical AQP1 expression occurs with cancer, injury, and neurodegenerative disease, but minimal information is available about the effects of normative aging on AQP1 expression. This study leverages tissues from the oldest-old rhesus macaques, some greater than 40 years of age, from the National Institute on Aging longitudinal study of...
Opal Stayer-Wilburn

Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging

3 weeks 4 days ago
Restricting the intake of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan in young or adult mice. However, their effects when initiated in aged animals are unknown. Here we investigate the consequences of consuming a diet with 67% reduction of all amino acids (low AA) or of isoleucine alone (low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. Both dietary regimens effectively promote overall metabolic health without reducing...
Chung-Yang Yeh

Transposable element 5mC methylation state of blood cells predicts age and disease

3 weeks 4 days ago
Transposable elements (TEs) are DNA sequences that expand selfishly in the genome, possibly causing severe cellular damage. While normally silenced, TEs have been shown to activate during aging. DNA 5-methylcytosine (5mC) is one of the main epigenetic modifications by which TEs are silenced and has been used to train highly accurate age predictors. Yet, one common criticism of such predictors is that they lack interpretability. In this study, we investigate the changes in TE 5mC methylation that...
Francesco Morandini

Study design features increase replicability in brain-wide association studies

3 weeks 4 days ago
Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behaviour associations^(1,2). Several recent studies have shown that thousands of study participants are required for good replicability of BWAS^(1-3). Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium⁴ (77,695 total scans) to demonstrate that optimizing study design is critical for increasing...
Kaidi Kang

Sociodemographic determinants of mobility decline among community-dwelling older adults: findings from the Canadian longitudinal study on ageing

3 weeks 4 days ago
CONCLUSION: Our study underscored the impact of modifiable and non-modifiable sociodemographic determinants of mobility trajectory. There is a need for nuanced ageing policies that support mobility in older adults, considering sociodemographic inequalities through equitable resource distribution, including people of lower socioeconomic backgrounds.
Ogochukwu Kelechi Onyeso