Table 1.

Experimental models of senescent cell deficiency/induction/depletion and their effects on renal outcomes

ReferenceRenal ModelModulation of SenescenceRenal Disease OutcomeEffect of Intervention
Baker et al.26Natural aging in INK-ATTAC miceINK-ATTAC +AP20187 or vehicle administration to deplete p16ink4a+ cells↑Glomerulosclerosis↓Glomerulosclerosis
ß-gal positivityß-gal positivity
Baar et al.71Natural-aging p16-3MR mice and fast-aging Xpd TTD/TTD miceFOXO4-DRI agent causes p53 nuclear exclusion. Ganciclovir treatment to p163MR mice causes p16ink4a-positive restricted cell death↑Serum ureaFOXO4-DRI or GCV to p16-3MR admin
↓Serum urea
↓Lmnb1 expression↑Lmnb1 expression
↑SASP expression (both XpdTTD/TTD and aged p16-3MR)↓SASP expression (both XpdTTD/TTD and aged p16-3MR)
Muñoz-Espín et al.13NephrogenesisWT versus P21cip1 KO mice with deficient growth arrest in nephrogenesisß-gal positivity in P21cip1 KO mice in uteroUse of PI3K inhibitor augments developmental senescence in WT mice
↑Ki67 expression but apoptosis maintains development
Wolstein et al.41UUOWT versus p16ink4a KO mice with impaired cell-cycle arrestUUO induces ß-gal positivity, apoptosis, and collagen deposition in WT miceß-gal positivity
↑Proliferation after UUO in p16ink4a KO
Megyesi et al.18Renal IRIWT versus P21cip1 KO mice with impaired cell-cycle arrestWT mice show tubular injury and raised blood urea levels after IRI↑Proliferation
↓Renal function
↑Mortality in P21cip1 KO
Lee et al.19Renal IRIWT versus p16ink4a/p19ARF double KO mice with impaired cell-cycle arrestWT mice show marked p16ink4a and p19ARF induction 28 d after IRI, with apoptosis and reduced tubular densityp16ink4a- and p19ARF-deficient mice show improved epithelial and microvascular repair, with increased myeloid cell recruitment
Al-Douahji et al.53DiabeticWT versus p21cip1 KOWT mice develop albuminuria and glomerular hypertrophyBoth p27kip1 KO and p21Cip1 KO mice were protected from proteinuria and glomerular expansion
Wolf et al.54NephropathyWT versus p27kip1 KO
Braun et al.66Renal transplantp16ink4a KO mice with impaired cell-cycle arrestWT mice develop interstitial fibrosis and tubular atrophyp16ink4a KO mice develop less atrophy and fibrosis after Tx
  • Transgenic and genetic knockout mice have been used to study the effect of (1) deficiencies in the induction of senescence or (2) depletion of established senescent cells. Several of these models are summarized in this table, with description of the experimental model of renal disease used, the alteration in senescence induction used, and any alterations in renal disease outcomes. TTD/TTD, trichothiodystrophy/trichothiodystrophy; GCV, ganciclovir; WT, wild-type; KO, knock-out; UUO, unilateral ureteric obstruction; IRI, ischemia-reperfusion injury; Tx, Transplant.