Wnt-induced, TRP53-mediated Cell Cycle Arrest of Precursors Underlies Interstitial Cell of Cajal Depletion During Aging.

ABSTRACT:

Background & aims

Gastric dysfunction in the elderly may cause reduced food intake, frailty, and increased mortality. The pacemaker and neuromodulator cells interstitial cells of Cajal (ICC) decline with age in humans, and their loss contributes to gastric dysfunction in progeric klotho mice hypomorphic for the anti-aging Klotho protein. The mechanisms of ICC depletion remain unclear. Klotho attenuates Wnt (wingless-type MMTV integration site) signaling. Here, we examined whether unopposed Wnt signaling could underlie aging-associated ICC loss by up-regulating transformation related protein TRP53 in ICC stem cells (ICC-SC).

Methods

Mice aged 1-107 weeks, klotho mice, APC^Δ468 mice with overactive Wnt signaling, mouse ICC-SC, and human gastric smooth muscles were st

SUBMITTER: Hayashi Y 

PROVIDER: S-EPMC7672319 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature