High glucose-induced replicative senescence: Point of no return and effect of telomerase

Shraga Blazer, Eli Khankin, Yardena Segev, Rachel Ofir, Michal Yalon-Hacohen, Zipora Kra-Oz, Yossi Gottfried, Sarit Larisch, Karl L. Skorecki

Research output: Contribution to journalArticlepeer-review


Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5 mM glucose (normoglycemia); addition of 16.5 mM D-glucose to a concentration of 22 mM (hyperglycemia); and addition of 16.5 mM L-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42 ± 1.5 PDs compared to 57.9 ± 3.83 PDs under normoglycemia (p < 0.0001). L-Glucose had no effect, suggesting that the effect of hyperglycemia was not attributed to hyperosmolarity. Activated caspase-3 measurement showed a significantly higher percentage of apoptotic cells in high glucose medium. Telomerase overexpression circumvented the effects of hyperglycemia on replicative capacity and apoptosis. The "point of no return," beyond which hyperglycemia resulted in irreversible progression to premature replicative senescence, occurred after exposure to hyperglycemia for as few as 20 PDs. These results may provide a biochemical basis for the relationship between hyperglycemia and those complications of diabetes, which are reminiscent of accelerated senescence.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by a grant (5210) from the Chief Scientist, Israeli Ministry of Health, and by a grant (180–341) from Technion V.P.R. Fund–Atkins Medical Research Fund for Gerontology. We gratefully acknowledge the valuable input and technical assistance of Dr. Sara Selig, Dr. Moshe Lewin, and Mrs. Shoshana Sperber.


  • Apoptosis
  • Diabetes
  • Hyperglycemia
  • Hyperosmolality
  • Replicative arrest
  • Senescence
  • Skin fibroblasts
  • Telomerase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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