Identification of markers for neurescence through transcriptomic profiling of postmortem human brains DOI
Shiva Kazempour Dehkordi, Sogand Sajedi, Amirreza Heshmat

et al.

Published: April 9, 2025

Abstract Neuronal senescence (i.e., neurescent) is an important hallmark of aging and neurodegeneration, but it remains poorly characterized in the human brain due to lack reliable markers. This study aimed identify neurescent markers based on single-nucleus transcriptome data from postmortem prefrontal cortex. Using eigengene approach, we integrated three gene panels: a) SenMayo, b) Canonical Senescence Pathway (CSP), c) Initiating (SIP), signatures. We found that paired outperform single markers; for instance, by combining CDKN2D ETS2 a decision tree, high accuracy 99% perfect specificity (100%) were achieved distinguishing neurescent. Differential expression analyses identified 324 genes are overexpressed These showed significant associations with neurodegeneration-related pathways including Alzheimer’s disease, Parkinson’s Huntington’s disease. Interestingly, several these linked mitochondrial dysfunction cytoskeletal dysregulation. findings provide valuable insights into complexities neurescent, emphasizing need further exploration histologically viable validation broader datasets.

Language: Английский

Chronic stress induces senescence build-up early in life DOI Creative Commons
Victor Lau, Ifeoluwa O. Awogbindin, Marie‐Ève Tremblay

et al.

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

Citations

0
Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities DOI Creative Commons

Hannah R. Hudson,

Xuehan Sun,

Miranda E. Orr

et al.

Neurotherapeutics, Journal Year: 2025, Volume and Issue: 22(3), P. e00519 - e00519

Published: Jan. 6, 2025

Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including toxic secretome and resistance to apoptosis. When form faster than they are cleared the immune system, accumulate in tissues throughout body contribute age-related diseases, neurodegeneration. This review highlights evidence of brain their role Alzheimer's disease (AD), leading cause dementia older adults. We also discuss progress challenges senotherapies, pharmacological strategies clear mitigate effects, which hold promise as interventions for AD related dementias (ADRD).

Language: Английский

Citations

0
Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration DOI Creative Commons
Jonathan Plessis‐Belair, Taylor Russo, Markus Rießland

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two these hallmarks, cell cycle dysregulation (CCD) nucleocytoplasmic transport (NCT) defects, long debated as being either causal or consequential in the pathology accelerated aging. Specifically, aberrant activation post-mitotic neurons has shown to trigger neuronal death pathways cellular senescence. Additionally, NCT observed be progressively dysregulated during aging neurodegeneration, where increased subcellular redistribution nuclear proteins such TAR DNA-Binding Protein-43 (TDP43) cytoplasm is primary driver many NDDs. However, functional significance defects consequence pathology, how machinery contributes remains unclear. Here, we describe that pharmacological inhibition importin-β import capable perturbing both mitotic lines vitro . Our Nemf R86S mouse model motor neuron disease, characterized further recapitulates hallmarks CCD , spinal vivo The consistent with transcriptional phenotypical senescence Together, this evidence suggests impairment resulting may common neurodegeneration. Graphical Abstract: Overview Dysregulated Cell Cycle Mechanisms Neuronal Cells. A block drives re-entry from G 0 culminating arrest at 1 /S. This associated CKIs INK locus (p15, p16, p18, p19) Cip/Kip (p21, p27) which act on specific CDK/Cyclin complexes. activity /S downregulation E2F stathmins, microtubule arrest.

Language: Английский

Citations

0
Identification of markers for neurescence through transcriptomic profiling of postmortem human brains DOI
Shiva Kazempour Dehkordi, Sogand Sajedi, Amirreza Heshmat

et al.

Published: April 9, 2025

Abstract Neuronal senescence (i.e., neurescent) is an important hallmark of aging and neurodegeneration, but it remains poorly characterized in the human brain due to lack reliable markers. This study aimed identify neurescent markers based on single-nucleus transcriptome data from postmortem prefrontal cortex. Using eigengene approach, we integrated three gene panels: a) SenMayo, b) Canonical Senescence Pathway (CSP), c) Initiating (SIP), signatures. We found that paired outperform single markers; for instance, by combining CDKN2D ETS2 a decision tree, high accuracy 99% perfect specificity (100%) were achieved distinguishing neurescent. Differential expression analyses identified 324 genes are overexpressed These showed significant associations with neurodegeneration-related pathways including Alzheimer’s disease, Parkinson’s Huntington’s disease. Interestingly, several these linked mitochondrial dysfunction cytoskeletal dysregulation. findings provide valuable insights into complexities neurescent, emphasizing need further exploration histologically viable validation broader datasets.

Language: Английский

Citations

0