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Replicative Cell Senescence

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...

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Related Experiment Video

Updated: Aug 2, 2025

Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts

Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts

Published on: January 2, 2018

Single-cell transcriptomic analysis uncovers diverse and dynamic senescent cell populations.

Noah Wechter¹, Martina Rossi¹, Carlos Anerillas¹

¹Laboratory of Genetics and Genomics, National Institute on Aging (NIA) Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, MD 21224, USA.

|April 22, 2023

Summary

Senescent cells contribute to aging diseases. This study used single-cell RNA sequencing to reveal diverse senescence programs and markers, aiding the development of targeted therapies for aging.

Keywords:

senescence single-cell analysis transcriptome

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Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry

Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry

Published on: April 6, 2022

Area of Science:

Cellular biology
Molecular biology
Gerontology

Background:

Cellular senescence, a state of irreversible growth arrest, is triggered by cell damage.
Accumulation of senescent cells is linked to aging and age-related diseases due to their secretion of inflammatory and matrix-remodeling proteins.
Identifying reliable markers for senescent cells is challenging due to the heterogeneous and dynamic nature of the senescent phenotype.

Purpose of the Study:

To comprehensively analyze the senescent transcriptome of human diploid fibroblasts at the single-cell level.
To identify distinct senescent cell subpopulations and dynamic transcriptional changes during senescence.
To investigate how proliferation status affects senescence pathways.

Main Methods:

Single-cell RNA sequencing (scRNA-seq) was employed on human diploid fibroblasts.
Analysis of cell states in cultures undergoing senescence induced by various stresses.
Tracking of transcriptomic dynamics during etoposide-induced senescence.

Main Results:

Distinct senescent cell subpopulations were identified, expressing mRNAs related to growth arrest, survival, and the secretory phenotype.
Two divergent senescence programs were discovered: one characterized by p16 (CDKN2A) mRNA expression, and another involving long noncoding RNAs and splicing dysregulation.
Evidence suggests that the proliferation status at senescence initiation influences the resulting senescence pathway.

Conclusions:

Cellular senescence exhibits diverse transcriptomic phenotypes at the single-cell level.
Understanding these distinct senescence programs and their regulation is crucial for developing targeted interventions against senescent cells.
This research provides a foundation for future therapeutic strategies aimed at mitigating the detrimental effects of senescent cells in aging and disease.