Senescent cells in the brain and where to find them

Rachmian, Noa; Krizhanovsky, Valery

doi:10.1111/febs.16649

Cited by 11 publications

(8 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cellular senescence is a process in which cells change their characteristic phenotype in response to stress and enter a state of prolonged cell cycle arrest accompanied by a distinctive secretory phenotype which can alter the tissue microenvironment and contribute to inflammation, oxidative stress, and tissue dysfunction ( Tchkonia et al, 2013 ; Rachmian and Krizhanovsky, 2022 ). It is known that senescent cells accumulate during obesity ( Minamino et al, 2009 ; Ogrodnik et al, 2017 ; Schafer et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

Salas-Venegas

Santín-Márquez

Ramírez-Carreto

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes that produce various pro-inflammatory molecules. These molecules cause chronic low-intensity inflammation, affecting the organism’s functioning and the central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during obesity occurs in different structures of the CNS involved in memory and learning, such as the cortex and the hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect CNS physiology, generating neuroinflammation and promoting cellular senescence establishment. Since some studies have shown an increase in senescent cells during aging, obesity, and neurodegenerative diseases, we proposed that cellular senescence participation may contribute to the cognitive decline in an obesity model of middle-aged female Wistar rats. The inflammatory state of 6 and 13 months-old female Wistar rats fed with a hypercaloric diet was measured in serum and CNS (cortex and hippocampus). Memory was evaluated using the novel object recognition (NOR) test; the presence of senescent markers was also determined. Our data suggest that the systemic inflammation generated by obesity induces a neuroinflammatory state in regions involved in learning and memory, with an increase in senescent markers, thus proposing senescence as a potential participant in the negative consequences of obesity in cognition.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

Salas-Venegas

Santín-Márquez

Ramírez-Carreto

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…This study suggests that targeting senescent cells may open new potential therapeutic strategies for AD, which might be effective even at late-disease stages. However, the senolytic drugs available today have limited applicability to humans due to their side effects 10,42 . In the future, developing new senolytic therapies that exclusively target senescent cells, or specifically, senescent microglia should be considered.…”

Section: Discussionmentioning

confidence: 99%

TREM2-dependent senescent microglia conserved in aging and Alzheimer’s disease

Rachmian

Medina

Cherqui

et al. 2023

Preprint

View full text Add to dashboard Cite

Dementia in general, and Alzheimer's disease (AD) in particular, are age-related diseases (1,2). AD is associated with multiple causative factors (3,4), among which local brain inflammation plays a significant role (5). Microglia, the brain-resident immune cells, are activated along the disease course (6,7). Yet, their contribution to the disease progression is still controversial. Here, using high-throughput mass cytometry for microglial immuno-phenotyping, we identified accumulation of senescent microglia in several pathologies associated with cognitive decline. These senescent microglia have a unique profile conserved across the multiple conditions investigated, including aging, mouse models of amyloidosis, and tauopathy. Moreover, we found that the expression of markers of senescence correlates with levels of TREM2, whose polymorphism was identified by GWAS as an AD risk factor (8,9). A TREM2-null AD mouse model showed lower levels of senescent microglia, relative to TREM2-intact AD mice. Senolysis using the drug ABT-73710,11 in an AD mouse model reduced the abundance of TREM2-senescent microglia without affecting levels of TREM2-dependent activated microglia, ameliorated cognitive deficits, and reduced brain inflammation. These results reveal the unexpected contribution of TREM2 to accumulation of senescent microglia in AD pathology, an effect that must be considered when targeting TREM2 as a therapeutic approach.

show abstract

“…As a consequence, SnCs from different tissues exhibit variations in both the composition and function of the SASP, and in the clearance process (Hernandez‐Segura et al., 2017 ; Ritschka et al., 2017 ; Storer et al., 2013 ; Victorelli et al., 2019 ). This observation may have clinical implications since different cell types from the same organ can undergo senescence, such as in kidneys (where senescence has been noted in tubular epithelial cells, endothelial cells, mesangial cells, and podocytes; Huang et al., 2022 ), liver (with reported senescence in hepatocytes, stellate cells, and cholangiocytes; Aravinthan & Alexander, 2016 ), lungs (with observed senescence in fibroblasts, epithelial cells, and endothelial cells) (Hansel et al., 2020 ), and brain (in which both glia and neurons can undergo senescence; Rachmian & Krizhanovsky, 2023 ). Therefore, given that the phenotype of SnCs from different tissues can differ within the same organ, a significant challenge in the field is to mitigate the detrimental effects of SnCs while preserving their beneficial roles.…”

Section: Heterogeneities Plasticity and Dynamics Of Cellular Senescencementioning

confidence: 99%

Subcellular structure, heterogeneity, and plasticity of senescent cells

Bitencourt,

Vargas,

Silva

et al. 2024

Aging Cell

View full text Add to dashboard Cite

Cellular senescence is a state of permanent growth arrest. It can be triggered by telomere shortening (replicative senescence) or prematurely induced by stresses such as DNA damage, oncogene overactivation, loss of tumor suppressor genes, oxidative stress, tissue factors, and others. Advances in techniques and experimental designs have provided new evidence about the biology of senescent cells (SnCs) and their importance in human health and disease. This review aims to describe the main aspects of SnCs phenotype focusing on alterations in subcellular compartments like plasma membrane, cytoskeleton, organelles, and nuclei. We also discuss the heterogeneity, dynamics, and plasticity of SnCs' phenotype, including the SASP, and pro‐survival mechanisms. We advance on the multiple layers of phenotypic heterogeneity of SnCs, such as the heterogeneity between inducers, tissues and within a population of SnCs, discussing the relevance of these aspects to human health and disease. We also raise the main challenges as well alternatives to overcome them. Ultimately, we present open questions and perspectives in understanding the phenotype of SnCs from the perspective of basic and applied questions.

show abstract

Senescent cells in the brain and where to find them

Cited by 11 publications

References 115 publications

Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

TREM2-dependent senescent microglia conserved in aging and Alzheimer’s disease

Subcellular structure, heterogeneity, and plasticity of senescent cells

Contact Info

Product

Resources

About