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Table 2 Studies of sepsis-induced senescence in cell, preclinical and clinical studies

From: Long-term cardiovascular complications following sepsis: is senescence the missing link?

Cells

Species of origin

Sepsis model

Analysis time points

Results

References

In vitro

     

 Microglia cells (BV2 cell)

C57BL/6 mouse

10 ng/ml LPS stimulation:

once

3 times: once every 48 h for 4 h each

6 times: once every 24 h for 4 h each

After 1, 6 or 12 days

Kinetics (6–12 days):

•Inhibition of cell proliferation

•Elevated degree of:

 − Cell cycle arrest in the G0/G1 phase

 − The aging associated proteins p53

 − Senescence-associated β-galactosidase activity

 − Senescence-associated heterochromatic foci (SAHF)

[92]

 Type II pulmonary alveolar epithelial cells (A549 immortalized cells)

Human

5—20 μg/ml LPS single stimulation for 24 h

After 1, 3 or 7 days

•Elevated degree of:

 − Senescence-associated β-galactosidase activity

•No decrease in telomere length

[89]

 Dental pulp stem cells (DPSCs)

Human

10 ng/ml Escherichia coli LPS (serotype 0111:B4) stimulation:

once for 6 h

3 times: once every 48 h for 6 h each

6 times: once every 24 h for 6 h each

After 1 h

Senescence-like morphology

•Inhibition of cell proliferation

•Elevated degree of:

 − Cell cycle arrest in the G1 phase

 − Senescence-associated β-galactosidase activity

 − The aging associated p16INK4A

 − of p16INK4A mRNA

•Knockdown of p16INK4A expression by siRNA transfection reversed the senescent features of LPS-treated DPSCs

[94]

 Adipocyte progenitors (stromal-vascular cells)

C57BL/6 mouse

0.2 μg/ml LPS stimulation for 24 h

After 3 days

•Elevated degree of:

 − p53 phosphorylation

 − Senescence-associated β-galactosidase activity

 − β-galactosidase-positive cells

 − mRNA indicating significant SAPS (TNFα, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and VEGFα)

No accelerate telomere shortening

[93]

Type II pulmonary alveolar epithelial cells (A549 immortalized cells)

Human nasopharyngeal cells (HEp-2 immortalized cells)

Human

Human respiratory syncytial virus (Pneumovirus genus of the Paramyxoviridae family)

After 48 h

•Senescence-associated secretory phenotype (SASP) in supernatant

•Elevated degree of:

 − The aging associated proteins p53

 − Senescence-associated β-galactosidase activity

[90]

Neuroblastoma Neuro2a Cells

Mouse

H7N9 Influenza A Virus 

After 3 days

•Senescent cell-like morphology

•Increase senescence-associated β-galactosidase activity

[91]

In vivo

     

 Blood, spleen and kidney samples (unspecified cell type)

Young male BALB/c mice

15 mg/kg LPS intraperitoneal injection

After 1 h or 48 h

•Dose-dependent telomere shortening in the spleen and liver at 48 h (but not at 1 h) measured by quantitative polymerase chain reaction (PCR)

•No difference in telomerase expression in kidney homogenates 1 h after LPS

[95]

 Lung tissue (unspecified cell type)

Young male C57BL/6 mice

Two-hit mouse model using CLP followed by sublethal Pseudomonas aeruginosa lung infection 4 h later

24 h after Pseudomonas aeruginosa lung infection

•Upregulation of:

 − Senescence-associated biomarker p16ink4a  − Senescence-associated β-galactosidase activity

[96]

 Vascular tissue

Young Wistar male rats

CLP

3, 7 or 90 days after CLP

•Upregulation of:

 − The aging associated proteins p53, p21 and p16

 − The aging associated proteins p53 localized in the endothelium

[34]