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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

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Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity

Mujib Ullah1,2, Zhongjie Sun1,3

  • 1Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Biomedical Research Center, Oklahoma City.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|November 20, 2018
PubMed

Insights

Klotho deficiency accelerates stem cell aging by impairing telomerase activity and telomere length. Cycloastragenol partially restored telomerase, indicating Klotho

Area of Science:

  • Gerontology and Stem Cell Biology
  • Molecular Mechanisms of Aging

Background:

  • Aging involves stem cell functional decline.
  • Klotho (KL) is an antiaging protein linked to extended lifespan.
  • The role of KL deficiency in stem cell aging requires elucidation.

Purpose of the Study:

  • To investigate if Klotho deficiency accelerates stem cell aging and telomere shortening.
  • To identify mechanisms linking KL deficiency to stem cell dysfunction.
  • To assess cycloastragenol's efficacy in restoring telomerase activity in aged stem cells.

Main Methods:

  • Klotho knockdown using siRNA.
  • Assessment of telomerase activity, differentiation potential, pluripotency, senescence, and apoptosis.
  • Analysis of gene expression (TERF1, TERT, POT1, TGFβ1, CD90, bFGF).
  • Evaluation of cycloastragenol treatment effects.

Main Results:

  • Klotho deficiency diminished telomerase activity and altered TERF1 and TERT expression.
  • KL deficiency impaired stem cell differentiation, pluripotency, and induced senescence and apoptosis.
  • Telomerase activity decreased with KL knockdown.
  • Cycloastragenol partially rescued telomerase deterioration.

Conclusions:

  • Klotho deficiency accelerates stem cell aging via reduced telomerase activity and telomere shortening.
  • KL and telomeres regulate stem cell aging through TERF1, POT1, and TERT, influenced by TGFβ, Insulin, and Wnt signaling.
  • KL plays a critical role in life extension by regulating telomere length and telomerase activity.
Keywords:
Adipose stem cellsAntiaging genesCD90CycloastragenolKlothoPluripotencyTelomerase enzymeTelomere

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