Related Experiment Video

Updated: Jun 4, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a

Eriko Nitta1, Masayuki Yamashita, Kentaro Hosokawa

  • 1Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Tokyo, Japan.

Blood
|February 8, 2011
PubMed

Insights

Telomerase reverse transcriptase (TERT) protects hematopoietic stem cells (HSCs) from aging through a telomere-independent mechanism. This study shows TERT mitigates aging by safeguarding HSCs under stress, preventing premature senescence and extending lifespan.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Hematology

Background:

  • Telomerase reverse transcriptase (TERT) is implicated in aging, but its precise role, independent of telomere lengthening, remains unclear.
  • Ataxia-telangiectasia mutated (ATM) is another key regulator of aging.
  • Understanding the interplay between TERT, ATM, and aging is crucial for developing interventions.

Purpose of the Study:

  • To investigate the combined roles of ATM and TERT in the aging process using a mouse model.
  • To elucidate the mechanisms by which TERT influences aging, particularly in hematopoietic stem cells (HSCs).
  • To determine if TERT's anti-aging effects are dependent on telomere length.

Main Methods:

  • Utilized ATM and TERT doubly deficient mice to assess aging phenotypes and lifespan.
  • Analyzed in vivo senescence markers, including p16(INK4a), p19(ARF), and p21.
  • Examined hematopoietic stem cell (HSC) function, reactive oxygen species (ROS) levels, apoptosis, and associated signaling pathways (p38MAPK, BCL-2).

Main Results:

  • ATM and TERT doubly deficient mice exhibited accelerated aging and reduced lifespan compared to ATM-null mice.
  • Accelerated aging was linked to in vivo senescence in hematopoietic tissues, dependent on p16(INK4a) and p19(ARF).
  • TERT deficiency in HSCs led to ROS fragility, increased apoptosis, and impaired stem cell function, suggesting a critical role for TERT in HSC protection.

Conclusions:

  • TERT mitigates aging by protecting HSCs from stress-induced damage via telomere length-independent mechanisms.
  • TERT's protective role in HSCs involves managing ROS and preventing apoptosis, partly through p38MAPK and BCL-2 pathways.
  • ATM and TERT act synergistically in regulating the aging process, with TERT playing a vital role in maintaining stem cell integrity.

More Related Videos

Semi-quantitative Detection of RNA-dependent RNA Polymerase Activity of Human Telomerase Reverse Transcriptase Protein08:26

Semi-quantitative Detection of RNA-dependent RNA Polymerase Activity of Human Telomerase Reverse Transcriptase Protein

Published on: June 12, 2018

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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 the telomeric...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...