Related Experiment Video

Updated: Apr 18, 2026

In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
18:48

In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients

Published on: August 12, 2017

15.0K

Gerosuppression in confluent cells

Olga V Leontieva1, Mikhail V Blagosklonny1

  • 1Department of Cell Stress Biology, Roswell Park Cancer Institute, Elms and Carlson Streets, Buffalo, NY 14263, USA.

Aging
|January 15, 2015
PubMed

Insights

Contact inhibition prevents cell senescence by inactivating mTOR (mechanistic target of rapamycin). Reactivating mTOR can trigger senescence, even in dense cultures, mimicking organismal gerosuppression.

Area of Science:

  • Cellular senescence
  • Cell cycle regulation
  • Gerontology

Background:

  • Contact inhibition is a physiological cell cycle arrest in dense cultures, yet it is poorly understood.
  • Contact-inhibited cells do not senesce, suggesting a mechanism suppressing senescence (geroconversion).
  • Mammalian target of rapamycin (mTOR) is inactive in contact-inhibited cells, suppressing geroconversion.

Purpose of the Study:

  • To extend the gerosuppression model by investigating senescence induction in contact-inhibited cells.
  • To explore the role of mTOR reactivation in etoposide-induced senescence in confluent cells.
  • To compare senescence suppression in vitro with gerosuppression observed in vivo.

Main Methods:

  • Induction of senescence using etoposide in cells at normal and high densities.
  • Manipulation of mTOR activity in confluent, contact-inhibited cells.
  • Analysis of senescence markers (p16, p21) and signaling pathways (mTOR, p-S6, p-Akt) in cell culture and murine tissues.

Main Results:

  • Etoposide induced senescence in normal cell density but failed in contact-inhibited cells.
  • Transient mTOR reactivation in etoposide-treated confluent cells promoted geroconversion.
  • p16, similar to p21, did not induce senescence in high cell density cultures.
  • Low p-S6 and high p-Akt levels in murine tissues mirrored suppressed geroconversion, contrasting with cell culture findings.

Conclusions:

  • Suppression of geroconversion in contact-inhibited cells mimics organismal gerosuppression.
  • mTOR activity is a key regulator of geroconversion, with its inactivation preventing senescence in dense cultures.
  • In vivo signaling (low p-S6, high p-Akt) supports the concept of inherent gerosuppression in tissues.

More Related Videos

Generation of Human Chimeric Antigen Receptor Regulatory T Cells10:29

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

2.7K
Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance14:01

Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance

Published on: July 22, 2011

15.1K

Related Concept Videos

Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.5K
Replicative Cell Senescence02:15

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...
4.7K
Replicative Cell Senescence02:15

Replicative Cell Senescence

3.5K
Cell Lines01:16

Cell Lines

A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...
11.3K
Transcytosis of IgG01:15

Transcytosis of IgG

Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
4.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
5.0K