Aging & Longevity

Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans

3 days 2 hours ago
Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with...
Seokjin Ham

Human alpha-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing

3 days 2 hours ago
Parkinson's disease (PD) is characterised by progressive loss of dopaminergic (DA) neurons from the substantia nigra (SN) and α-synuclein (αSyn) accumulation. Age is the biggest risk factor for PD and may create a vulnerable pre-parkinsonian state, but the drivers of this association are unclear. It is known that ageing increases αSyn expression in DA neurons and that this may alter molecular processes that are central to maintaining nigrostriatal integrity. To model this, adult female...
Noelia Morales-Prieto

Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan in Saccharomyces cerevisiae

4 days 2 hours ago
A major consequence of aging and stress, in yeast to humans, is an increased accumulation of protein aggregates at distinct sites within the cells. Using genetic screens, immunoelectron microscopy, and three-dimensional modeling in our efforts to elucidate the importance of aggregate annexation, we found that most aggregates in yeast accumulate near the surface of mitochondria. Further, we show that virus-like particles (VLPs), which are part of the retrotransposition cycle of Ty elements, are...
K L Schneider

The genetic architecture of multimodal human brain age

5 days 2 hours ago
The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10^(-8)). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and...
Junhao Wen

Design and validation of a reporter mouse to study the dynamic regulation of TFEB and TFE3 activity through <em>in vivo</em> imaging techniques

5 days 2 hours ago
TFEB and TFE3 belong to the MiT/TFE family of transcription factors that bind identical DNA responsive elements in the regulatory regions of target genes. They are involved in regulating lysosomal biogenesis, function, exocytosis, autophagy, and lipid catabolism. Precise control of TFEB and TFE3 activity is crucial for processes such as senescence, stress response, energy metabolism, and cellular catabolism. Dysregulation of these factors is implicated in various diseases, thus researchers have...
Electra Brunialti

Resting-State Functional Connectivity of the Motor and Cognitive Areas is Preserved in Masters Athletes

5 days 2 hours ago
Aging is characterized by a decline in physical and cognitive functions, often resulting in decreased quality of life. Physical activity has been suggested to potentially slow down various aspects of the aging process, a theory that has been supported by studies of Masters Athletes (MA). For example, MA usually have better cognitive and physical functions than age-matched sedentary and healthy older adults (OA), making them a valuable model to gain insights into mechanisms that promote physical...
Alexandra Potvin-Desrochers

Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging

6 days 2 hours ago
Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis...
Katalin Todorov-Völgyi

Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology

6 days 2 hours ago
The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial-derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity. Our research uncovered a unique humanin variant, P3S, specifically enriched in centenarians with the APOE4 allele. Through in silico analyses and subsequent experimental...
Brendan Miller

Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice

6 days 2 hours ago
Nucleolar stress (NS) has been associated with age-related diseases such as cancer or neurodegeneration. To investigate how NS triggers toxicity, we used (PR)n arginine-rich peptides present in some neurodegenerative diseases as inducers of this perturbation. We here reveal that whereas (PR)n expression leads to a decrease in translation, this occurs concomitant with an accumulation of free ribosomal (r) proteins. Conversely, (PR)n-resistant cells have lower rates of r-protein synthesis, and...
Oleksandra Sirozh

Global fertility in 204 countries and territories, 1950-2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

6 days 2 hours ago
BACKGROUND: Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global...
GBD 2021 Fertility and Forecasting Collaborators

CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa

1 week ago
Retinitis pigmentosa (RP) is one of the most common forms of hereditary neurodegeneration. It is caused by one or more of at least 3,100 mutations in over 80 genes that are primarily expressed in rod photoreceptors. In RP, the primary rod-death phase is followed by cone death, regardless of the underlying gene mutation that drove the initial rod degeneration. Dampening the oxidation of glycolytic end products in rod mitochondria enhances cone survival in divergent etiological disease models...
Nicholas D Nolan

Optical coherence tomography as a potential surrogate marker of dopaminergic modulation across the life span

1 week ago
The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation of the retina, shows promise to be used as a surrogate marker of dopaminergic neuromodulation in cognition. Overall, most evidence supports reduced...
Julia Elmers

Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation

1 week ago
Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear....
Wayne Mitchell

Variable aging and storage of dissolved black carbon in the ocean

1 week ago
During wildfires and fossil fuel combustion, biomass is converted to black carbon (BC) via incomplete combustion. BC enters the ocean by rivers and atmospheric deposition contributing to the marine dissolved organic carbon (DOC) pool. The fate of BC is considered to reside in the marine DOC pool, where the oldest BC ^(14)C ages have been measured (>20,000 ^(14)C y), implying long-term storage. DOC is the largest exchangeable pool of organic carbon in the oceans, yet most DOC (>80%) remains...
Alysha I Coppola

Age-related cholesterol and colorectal cancer progression: Validating squalene epoxidase for high-risk cases

1 week ago
As people age, the risk and progression of colorectal cancer (CRC), along with cholesterol levels, tend to increase. Nevertheless, epidemiological studies on serum lipids and CRC have produced conflicting results. We previously demonstrated that the reduction of squalene epoxidase (SQLE) due to accumulated cholesterol within cells accelerates CRC progression through the activation of the β-catenin pathway. This study aimed to investigate the mechanism by which age-related cholesterol...
Soo Young Jun

Alzheimer's Drugs APPlication for Down syndrome?

1 week 1 day ago
Accumulation of the amyloid β (Aβ) peptide, derived from Aβ precursor protein (APP), is a trait of Down syndrome (DS), as is early development of dementia like Alzheimer's disease (AD). Treatments for AD in DS simply do not exist. New drug therapies for AD, e.g., Lecanemab, are monoclonal antibodies designed to clear amyloid plaques composed of Aβ. The increasingly real ability to target and dispose of Aβ favors the use of these drugs in individuals with DS for AD, perhaps as earlier...
Debomoy K Lahiri

Vascular dementia: From pathobiology to emerging perspectives

1 week 1 day ago
Vascular dementia (VaD) is the second most common type of dementia. VaD is synonymous with ageing, and its symptoms place a significant burden on the health and wellbeing of older people. Despite the identification of a substantial number of risk factors for VaD, the pathological mechanisms underpinning this disease remain to be fully elucidated. Consequently, a biogerontological imperative exists to highlight the modifiable lifestyle factors which can mitigate against the risk of developing...
Amy Elizabeth Morgan
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