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The spatial landscape of glial pathology and T cell response in Parkinson's disease substantia nigra

2 months 1 week ago
Parkinson's Disease (PD) is an incurable neurodegenerative disease that causes movement disorders. Neurons in PD aggregate α-synuclein and are depleted from the substantia nigra (SN), which is a movement control hub. The presence of α-synuclein-reactive T cells in PD patient blood suggests a role for adaptive immunity in the pathogenesis of PD. However, the characteristics of this response within the brain are not well understood. Here, we employed single-nucleus RNAseq, spatial transcriptomics,...
Maxwell Ma

Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer's disease

2 months 1 week ago
Caloric restriction slows or prevents Alzheimer's disease in animal models. Calorie restriction is typically implemented in rodents through feeding once per day; as the animals quickly consume their food, they are subject to a prolonged self-imposed fasting period between meals. Here, we examine the distinct contributions of fasting and reduced calories to the beneficial effects of calorie restriction on Alzheimer's disease by placing male and female 3xTg and non-transgenic control mice on a...
Reji Babygirija

Telomerase dynamics in stem cells: Unraveling the molecular nexus of cellular aging and regeneration

2 months 1 week ago
The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in...
Yanhua Jiang

Lysosomal membrane homeostasis and its importance in physiology and disease

2 months 1 week ago
Lysosomes are membranous organelles that are crucial for cell function and organ physiology. Serving as the terminal stations of the endocytic pathway, lysosomes have fundamental roles in the degradation of endogenous and exogenous macromolecules and particles as well as damaged or superfluous organelles. Moreover, the lysosomal membrane is a docking and activation platform for several signalling components, including mTOR complex 1 (mTORC1), which orchestrates metabolic signalling in the cell....
Maja Radulovic

Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling

2 months 1 week ago
Frailty is a multifaceted clinical state associated with accelerated aging and adverse health outcomes. Informed etiological models of frailty hold promise for producing widespread health improvements across the aging population. Frailty is currently measured using aggregate scores, which obscure etiological pathways that are only relevant to subcomponents of frailty. Here we perform a multivariate genome-wide association study of the latent genetic architecture between 30 frailty deficits,...
Isabelle F Foote

Characterizing sarcopenia and sarcopenic obesity in patients aged 65 years and over, at risk of mobility disability: a multicenter observational trial (SARA-OBS)

2 months 1 week ago
CONCLUSIONS: SARA-OBS results contribute to defining subgroups of older adults at risk of functional decline over 6 months, specifically subjects with SPPB = 8, affecting GS and the 6MWD. Additionally, the SO subpopulation exhibited a relevant deterioration in physical function as evaluated by the 6MWD.
Roger A Fielding

Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species

2 months 1 week ago
Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is...
Jongsun Lee

Autophagy activator AA-20 improves proteostasis and extends Caenorhabditis elegans lifespan

2 months 1 week ago
The degradation of cellular components through autophagy is essential for longevity and healthy aging. However, autophagy function decreases with aging, contributing to age-related diseases. In this study, we characterized a small-molecule activator of autophagy called AA-20 that enhances autophagy and lipid droplet clearance in human cells and in the nematode Caenorhabditis elegans. AA-20 reduces polyglutamine aggregation in an autophagy-dependent manner in both human cells and C. elegans,...
Ee Phie Tan

Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species

2 months 1 week ago
Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of messenger RNA (mRNA) homeostasis and protein synthesis. Defects in RQC are implicated in cellular dysfunction and proteotoxicity, but their impact on aging remains elusive. Here, we show that Pelota, the ribosome rescue factor, promotes longevity and protects against age-related pathological phenotypes in multiple metazoan species. By performing a targeted genetic screen, we find that Pelota is...
Jongsun Lee