Table 2 Senescent pathways and outcomes in cardiac, hepatic, and brain ischemia/reperfusion injury.

Heart

C57BL/6J mice;

LAD ischemia 60 min and reperfusion 24 h, 72 h, 1w, 4w

p16/pRb pathway

P53/p21 pathway

Cardiac senescence ↑ (SA-β-gal ↑, SASP, p16^INK4A ↑, p21^CIP1 ↑)

Cardiac function↓

[56]

Heart

C57BL/6J mice;

Coronary artery ischemia 1d, 2d, 7d, 28d

p53/p21 pathway

p16/pRb pathway

Cardiac senescence ↑ (SASP ↑, p53 ↑, p21 ^CIP1 ↑, p16 ^INK4A ↑)

[72]

Heart

In vivo: C57BL/6J mice;

LCA ischemia 45 min and reperfusion 24 h

In vitro: Neonatal rat cardiomyocytes;

Hypoxia 12 h and reoxygenation 24 h

p53/p21 pathway

p16/pRb pathway

In vivo: Cardiac senescence ↑ (SA-β-gal ↑, SASP ↑, p16 ^INK4A ↑, p53 ↑, p19 ↑)

Cardiac function↓

In vitro: Cardiac senescence ↑ (SA-β-gal ↑, SASP ↑, p16 ^INK4A ↑, p53 ↑, p19 ↑)

[123]

Heart

In vivo: C57BL/6 mice;

LAD ischemia 7d

In vitro: Primary mice cardiomyocytes;

H₂O₂ culture 24 h

p53/p21 pathway

p16/pRb pathway

In vivo: Cardiac senescence ↑ (SASP ↑, p53 ↑, p16 ^INK4A ↑)

Cardiac function↓

In vitro: Cardiac senescence ↑ (SA-β-gal ↑, p53 ↑, p16 ^INK4A ↑)

[143]

Heart

In vivo: mice and rats;

LAD ischemia 1w, 4w;

In vitro: neonatal rat cardiomyocytes;

hypoxia 16 h and reoxygenation 10 h

p53/p21 pathway

In vivo: Cardiac senescence ↑ (p53 ↑, SA-β-gal ↑)

Cardiac function↓

Cardiac fibrosis↑

In vitro: Cardiac senescence ↑ (SA-β-gal ↑, p53 ↑)

[43]

Heart

C57BL/6 mice;

LAD ischemia 1d, 1w, 2w, 4w

p53/p21 pathway

p16/pRb pathway

Cardiac senescence ↑ (SA-β-gal ↑, SASP ↑, p16 ^INK4A ↑, p53↑ and p21^CIP1 ↑)

[98]

Heart

C57BL/6N mice;

TAC 2w, 6 w

p53/p21 pathway

p16/pRb pathway

Cardiac senescence ↑ (SA-β-gal ↑, p16 ^INK4A ↑, p21^CIP1 ↑)

[144]

Liver

In vivo: C57/B6 mice;

Partial hepatectomy, ischemia 1 h and reperfusion 6 h, 1d, 3d, 5d

In vitro: hiPSC-MSCs cell line

H₂O₂ culture 2 h and normal medium culture 48 h

p16/pRb pathway

In vivo: Hepatic senescence ↑ (SA-β-gal ↑, p16 ^INK4A ↑)

Hepatic function↓

In vitro: Hepatic senescence ↑ (SA-β-gal ↑, p16 ^INK4A ↑)

[57]

Brain

Adult male Wistar rats

tMCAO ischemia 1 h and reperfusion 24 h, 3 and 7 d

p53/p21 pathway

p16/pRb pathway

In vitro: Cerebral senescence ↑ (lipofuscin granules ↑, SASP ↑, p16 ^INK4A ↑, p53↑ and p21^CIP1 ↑)

[99]

Brain

In vivo: Male Sprague–Dawley rats;

left MCAO ischemia 1 h and reperfusion 4d

In vitro: Rat brain cortex astrocytes

Oxygen-Glucose Deprivation 4 h and Reoxygenation 20 h

p16/pRb pathway

In vivo: Cerebral senescence ↑ (SASP ↑, p16 ^INK4A ↑)

Inflammation ↑ (NOS2 ↑, MPO ↑)

neurological functions↓

In vitro: Cerebral senescence ↑ (SA-β-gal ↑)

[102]

Brain

In vivo: CD1 male mices;

tMCAO ischemia 1 h and reperfusion 30 min and 72 h

p53/p21 pathway

p16/pRb pathway

Cerebral senescence ↑ (p16 ↑, p21 ↑)

Inflammation ↑ (TNFɑ↑, IL6 ↑, Cxcl1 ↑)

[100]