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.2021 Nov;48(5):199.
doi: 10.3892/ijmm.2021.5032. Epub 2021 Sep 13.

Reversal of brain aging by targeting telomerase: A nutraceutical approach

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Reversal of brain aging by targeting telomerase: A nutraceutical approach

Dimitris Tsoukalas et al. Int J Mol Med.2021 Nov.

Abstract

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age‑related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containingCentella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18‑month‑old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR‑ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle‑aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Keywords: Centella asiatica; aging; telomerase activators; telomerase reverse transcriptase; vitamin D; vitamin C; zinc.

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Conflict of interest statement

DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. DT is a scientific advisor for Natural Doctor S.A. The other authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Workflow of the study design. TRAP, telomeric repeat amplification protocol; TERT, telomerase reverse transcriptase.
Figure 2
Figure 2
Telomerase activity following 3 months of treatment expressed as absorbance units (A450 nm). (A) In the cerebellum and (B) in the cortex.*P<0.05 and**P<0.01.
Figure 3
Figure 3
TERT protein level in (A) the cerebellum; and (B) the cortex.*P<0.05. TERT, telomerase reverse transcriptase.
Figure 4
Figure 4
Telomerase reverse transcriptase immunoreactivity in the cytoplasm and nucleus of brain cells in the cortex (brown color; magnification, ×20), 3,3′-diaminobenzidine staining. (A) Young control group; (B) old-aged control group; (C) old-aged group 1; (D) old-aged group 2.
Figure 5
Figure 5
Microscopic structure of the cerebral cortex. (A) Young control group. Fragment with the microscopic structure of the cerebral cortex with normal differentiation. H&E staining; magnification, ×100. (B) Young control group. More detailed view of the image in panel A. H&E staining; magnification, ×200. (C) Old-aged control group. Fragment with the microscopic structure of the cerebral cortex with cytoarchitectonic structure modified by edema and a poor neuronal cell distribution is shown. H&E staining; magnification, ×100. (D) Old-aged control group. More detailed view of the image in panel C, with rare large and medium pyramidal neurons dissociated by marked edema. H&E staining; magnification, ×200. H&E, hematoxylin and eosin.
Figure 6
Figure 6
Microscopic structure of the cerebral cortex. (A) Old-aged group 1. Fragment of the microscopic structure of cerebral cortex with cytoarchitectonic structure modified by edema and poor neuronal cellular distribution is shown. H&E staining; magnification, ×100. (B) Old-aged group 1. More detailed view of the image in panel A, with the identification of cerebral cortex layers. H&E staining; magnification, ×200. (C) Old-aged group 2. Fragment of the microscopic structure of the cerebral cortex with relative normal cytoarchitectonic structure is shown. H&E staining; magnification, ×100; (D) More detailed view of the image in panel C, with the identification of the deep layers of the cerebral cortex. H&E staining; magnification, ×200. H&E, hematoxylin and eosin.
Figure 7
Figure 7
Microscopic structure of the cerebellar cortex. (A) Young control group. Fragment of the microscopic structure of cerebellar cortex with normal differentiation is shown. H&E staining; magnification, ×100. (B) Young control group. More detailed view of the image in panel A, in which the layers of the cerebellar cortex are observed. H&E staining; magnification, ×200. (C) Old-aged control group. Fragment of the microscopic structure of the cerebellar cortex with the modified architecture of the layers of the cerebellar cortex is shown. H&E staining; magnification, ×100; (D) Old-aged control group. More detailed view of the image in panel C, in which the modification of the architecture of the layers of the cerebellar cortex is observed, with increased interneuronal edema. H&E staining; magnification, ×200. H&E, hematoxylin and eosin.
Figure 8
Figure 8
Microscopic structure of the cerebellar cortex. (A) Old-aged group 1. Fragment of the microscopic structure of the cerebellar cortex with the modified architecture of the layers of the cerebellar cortex with discrete interneuronal edema is shown. H&E staining; magnification, ×100. (B) Old-age group 1. More detailed view of the image in panel A. H&E staining; magnification, ×200. (C) Old-aged group 2. Fragment of the microscopic structure of cerebellar cortex with a relatively normal cytoarchitectonic structure is shown. H&E staining; magnification, ×100. (D) More detailed view of the image in panel C revealing the layers of the cerebellar cortex. H&E staining; magnification, ×200. H&E, hematoxylin and eosin.
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