Klotho Deficiency Accelerates Stem Cells Aging by Impairing Telomerase Activity.
Adipose stem cells
Antiaging genes
CD90
Cycloastragenol
Klotho
Pluripotency
Telomerase enzyme
Telomere
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
16 08 2019
16 08 2019
Historique:
received:
02
12
2017
pubmed:
20
11
2018
medline:
12
6
2020
entrez:
20
11
2018
Statut:
ppublish
Résumé
Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGFβ, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGFβ1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.
Identifiants
pubmed: 30452555
pii: 5188011
doi: 10.1093/gerona/gly261
pmc: PMC6696722
doi:
Substances chimiques
Telomerase
EC 2.7.7.49
Glucuronidase
EC 3.2.1.31
Klotho Proteins
EC 3.2.1.31
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1396-1407Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL118558
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122166
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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