Aging & Longevity

Accurate age prediction from blood using a small set of DNA methylation sites and a cohort-based machine learning algorithm

1 day 2 hours ago
Chronological age prediction from DNA methylation sheds light on human aging, health, and lifespan. Current clocks are mostly based on linear models and rely upon hundreds of sites across the genome. Here, we present GP-age, an epigenetic non-linear cohort-based clock for blood, based upon 11,910 methylomes. Using 30 CpG sites alone, GP-age outperforms state-of-the-art models, with a median accuracy of ∼2 years on held-out blood samples, for both array and sequencing-based data. We show that...
Miri Varshavsky

The menopausal transition period and cardiovascular risk

1 day 2 hours ago
The menopausal transition period spans, on average, 2-8 years before the final menstrual period and is associated with an increase in clinical and subclinical cardiovascular risk. In this Review, we discuss the metabolic and cardiovascular changes that occur during the menopausal transition period and the role of ovarian ageing, chronological ageing and other ageing-related risk factors in mediating these changes. Disentangling the relative contributions of chronological and reproductive ageing...
Jaya M Mehta

Ribosome-binding antibiotics increase bacterial longevity and growth efficiency

1 day 2 hours ago
Antibiotics, by definition, reduce bacterial growth rates in optimal culture conditions; however, the real-world environments bacteria inhabit see rapid growth punctuated by periods of low nutrient availability. How antibiotics mediate population decline during these periods is poorly understood. Bacteria cannot optimize for all environmental conditions because a growth-longevity tradeoff predicts faster growth results in faster population decline, and since bacteriostatic antibiotics slow...
Emily Wood

Senolytic treatment reduces oxidative protein stress in an aging male murine model of post-traumatic osteoarthritis

1 day 2 hours ago
Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53/MDM2 interaction inhibitor,...
Alexander F Chin

APOEε4 potentiates amyloid β effects on longitudinal tau pathology

2 days 2 hours ago
The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([^(18)F]AZD4694) and tau...
João Pedro Ferrari-Souza

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan

2 days 2 hours ago
CD8^(+) T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8^(+) T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M1(58-66) (A2/M1(58)) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older...
Carolien E van de Sandt

APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints

2 days 2 hours ago
The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice...
Zhuoran Yin

ADAR-mediated regulation of PQM-1 expression in neurons impacts gene expression throughout C. elegans and regulates survival from hypoxia

2 days 2 hours ago
The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal's surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues....
Ananya Mahapatra

Impairments in endogenous AMPA receptor dynamics correlates with learning deficits in Alzheimer's disease model mice

2 days 2 hours ago
AMPA receptors (AMPARs) play a critical role in synaptic plasticity and learning and memory, and dysfunction or dysregulation of AMPARs could lead to various neurological and psychiatric disorders, such as Alzheimer's disease (AD). However, the dynamics and/or longitudinal changes of AMPARs in vivo during AD pathogenesis remain elusive. Here, employing 5xFAD SEP-GluA1 KI mice, we investigated endogenous AMPA receptor dynamics in a whisker deflection-associated Go/No-go learning paradigm. We...
Kongjie Lu

Incongruence between transcriptional and vascular pathophysiological cell states

2 days 2 hours ago
The Notch pathway is a major regulator of endothelial transcriptional specification. Targeting the Notch receptors or Delta-like ligand 4 (Dll4) dysregulates angiogenesis. Here, by analyzing single and compound genetic mutants for all Notch signaling members, we find significant differences in the way ligands and receptors regulate liver vascular homeostasis. Loss of Notch receptors caused endothelial hypermitogenic cell-cycle arrest and senescence. Conversely, Dll4 loss triggered a strong...
Macarena Fernández-Chacón

Silc1 long noncoding RNA is an immediate-early gene promoting efficient memory formation

3 days 2 hours ago
Long noncoding RNAs (lncRNAs) are expressed in many brain circuits and types of neurons; nevertheless, their functional significance for normal brain functions remains elusive. Here, we study the functions in the central nervous system of Silc1, an lncRNA we have shown previously to be important for neuronal regeneration in the peripheral nervous system. We found that Silc1 is rapidly and strongly induced in the hippocampus upon exposure to novelty and is required for efficient spatial learning....
Rotem Ben-Tov Perry

Age-dependent effects of dopamine on working memory and synaptic plasticity in hippocampal CA3-CA1 synapses in mice

4 days 2 hours ago
Normal aging in mammals is accompanied by a decline in learning and memory. Dopamine plays a vital role in regulating cognitive functions, but it declines with age: During non-pathological aging, dopamine levels, receptors, and transporters decrease. Regarding the role of the dopaminergic system's changes in old age, we examined the effect of age and applied dopamine on working memory, synaptic transmission, and long-term potentiation (LTP) induction and maintenance in young adult and mature...
Fatemeh Bakhtiarzadeh

Aging and urinary control: Alterations in the brain-bladder axis

4 days 2 hours ago
Age-associated alterations in bladder control affect millions of older adults, with a heavy burden added to families both economically and in quality of life. Therapeutic options are limited with poor efficacy in older adults, lending to a growing need to address the gaps in our current understanding of urinary tract aging. This review summarizes the current knowledge of age-associated alterations in the structure and function of the brain-bladder axis and identifies important gaps in the field...
Cara C Hardy

Acetylation discriminates disease-specific tau deposition

5 days 2 hours ago
Pathogenic aggregation of the protein tau is a hallmark of Alzheimer's disease and several other tauopathies. Tauopathies are characterized by the deposition of specific tau isoforms as disease-related tau filament structures. The molecular processes that determine isoform-specific deposition of tau are however enigmatic. Here we show that acetylation of tau discriminates its isoform-specific aggregation. We reveal that acetylation strongly attenuates aggregation of four-repeat tau protein, but...
Pijush Chakraborty

Altered ubiquitin signaling induces Alzheimer's disease-like hallmarks in a three-dimensional human neural cell culture model

5 days 2 hours ago
Alzheimer's disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB^(+1)), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem. We now detect UBB^(+1) in human brains during early AD stages. Our study employs a 3D neural culture platform derived from human neural...
Inbal Maniv

Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis

5 days 2 hours ago
Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients (mean age 58.7 ± 11.0 years; 47.5% male) with T2D were...
Byeong Chang Sim

Functional characterization of Alzheimer's disease genetic variants in microglia

6 days 2 hours ago
Candidate cis-regulatory elements (cCREs) in microglia demonstrate the most substantial enrichment for Alzheimer's disease (AD) heritability compared to other brain cell types. However, whether and how these genome-wide association studies (GWAS) variants contribute to AD remain elusive. Here we prioritize 308 previously unreported AD risk variants at 181 cCREs by integrating genetic information with microglia-specific 3D epigenome annotation. We further establish the link between functional...
Xiaoyu Yang

The VCAM1-ApoE pathway directs microglial chemotaxis and alleviates Alzheimer's disease pathology

6 days 2 hours ago
In Alzheimer's disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. Although extrinsic signals, including interleukin-33 (IL-33), can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ)...
Shun-Fat Lau
3 hours 56 minutes ago
Aging Research Papers: Latest results from PubMed
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