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. 2025 Sep 4;26(5):178.
doi: 10.1007/s10522-025-10315-x.

Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity

Sarah Al-Dulaimi  1 , Ross Thomas  1 , Sheila Matta  2 , Terry Roberts  3
Affiliations

Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity

Sarah Al-Dulaimi et al. Biogerontology. .

Erratum in

Abstract

Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mammalian cells. This happens through the induction of telomerase enzyme activity, resulting in the extension of telomere length. A strong link exists between telomere length and aging-related diseases. Therefore, telomeres are considered to be one of the biomarkers of aging, and increasing or maintaining telomere length may contribute to healthy aging and longevity. Epitalon has been the subject of several anti-aging studies however, quantitative data on the biomolecular pathway leading to telomere length increase, hTERT mRNA expression, telomerase enzyme activity, and ALT activation have not been extensively studied in different cell types. In this article, the breast cancer cell lines 21NT, BT474, and normal epithelial and fibroblast cells were treated with epitalon then DNA, RNA, and proteins were extracted. qPCR and Immunofluorescence analysis demonstrated dose-dependent telomere length extension in normal cells through hTERT and telomerase upregulation. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation. Only a minor increase in ALT activity was observed in Normal cells, thereby showing that it was specific to cancer cells. Our data suggests that epitalon can extend telomere length in normal healthy mammalian cells through the upregulation of hTERT mRNA expression and telomerase enzyme activity.

Keywords: ALT; Mammalian cells; Telomerase; Telomere length.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Telomere length of breast cancer cells and normal cells treated with epitalon. A 21NT cells B BT474 cells. Both cells were treated for 4 days with varying concentrations of epitalon. (0.1, 0.2, 0.5 and 1 ug/ml). Untreated cells were used as a control. C Telomere length of IBR.3 cells (P.14) treated with 1 μg /ml epitalon for 3 weeks. D telomere length of HMEC (P.14) treated with 1 μg /ml epitalon for 3 weeks. Untreated cells were included as a control
Fig. 2
Fig. 2
hTERT expression (RQ) and telomerase enzyme activity in breast cancer cells and normal fibroblast cells treated with epitalon. A and B hTERT expression and telomerase activity for 21NT treated with 0.5 and 1 μg/ml of epitalon for 4 days. C and D hTERT expression and telomerase activity of BT474 treated with 0.5 and 1 μg/ml of epitalon for 4 days. PC3 was included as a positive control for telomerase activity. E and F hTERT expression and telomerase activity for IBR.3 were treated with 1 μg/ml of epitalon for three weeks. G and H hTERT expression and telomerase activity for HMEC treated with 1 ug/ml of epitalon for three weeks
Fig. 3
Fig. 3
ALT activity in breast cancer cells and normal cells treated with epitalon. A and B ALT activity in 21NT and BT474 treated with 1 μg/ml of epitalon for 4 days. Untreated cells and the ALT positive U2OS were included as controls. C IBR.3 and D HMEC treated with 1 μg/ml of epitalon for three weeks. E Immunofluorescence to detect PML bodies in 21NT and BT474 cells treated with epitalon for 4 days. The colocalization PML bodies (green staining) within the nucleus (blue staining) for 21NT and BT474 treated with epitalon indicated the presence of ALT. PML bodies were detected using Lecia microscope with X 100 objective
Fig. 3
Fig. 3
ALT activity in breast cancer cells and normal cells treated with epitalon. A and B ALT activity in 21NT and BT474 treated with 1 μg/ml of epitalon for 4 days. Untreated cells and the ALT positive U2OS were included as controls. C IBR.3 and D HMEC treated with 1 μg/ml of epitalon for three weeks. E Immunofluorescence to detect PML bodies in 21NT and BT474 cells treated with epitalon for 4 days. The colocalization PML bodies (green staining) within the nucleus (blue staining) for 21NT and BT474 treated with epitalon indicated the presence of ALT. PML bodies were detected using Lecia microscope with X 100 objective
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