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Is telomerase a hidden player? Therapeutic potential of natural telomerase activators against age-related diseases

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Abstract

There is a huge demand for novel treatment and/or prevention approaches for age-related diseases, which reduce life quality and one of the main reasons for death worldwide. Many age-related diseases were found to be associated with dysfunctional telomeres, which accelerate aging process due to the decrease in repair potential of tissues. An enzyme called telomerase is mainly responsible for keeping telomeres healthful. In the last two decades, the progress in the field, including in vitro studies, preclinical data, and human trials, demonstrated that telomerase and related genes might be powerful targets for the treatment of those diseases. Considering telomerase reactivation as a treatment strategy in age-related degenerative diseases, telomerase activators obtained from natural products stand out as promising agents. Although various research showed that those activators have protective/therapeutic activity against age-related diseases, the role of telomerase activation is often neglected in studies. In this context, we focused on the natural products as telomerase activator and their activities on age-related diseases, specifically neurodegenerative, cardiovascular, and osteodegenerative disorders, in which telomere dysfunction plays a causal role. Thus, this review aims to draw attention to the possibility of telomerase activation in therapy, in which some well-known natural products such as telomerase activators might play a role.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

AAV:

Adeno-associated virus

AD:

Alzheimer’s disease

AD-MSC:

Adipose derived-MSC

Akt:

Protein kinase B

ALS:

Amyotrophic lateral sclerosis

AMPK:

AMP-activated protein kinase

AQPs:

Aquaporins

ARE:

Antioksidant response element

AST IV:

Astragaloside IV

Aβ:

Amyloid-beta peptide

BM-MSC:

Bone marrow-derived-MSC

CA:

Cycloastragenol

CAE:

Centella asiatica extract

CNS:

Central nervous system

CREB:

CAMP response element binding protein

EGFR:

Epidermal growth factor receptor

ERK:

Ras-extracellular signal-regulated kinase

ESC:

Embryonic stem cell

GABA:

Gamma-aminobutyric acid

GBE:

Ginkgo biloba extract

GSH:

Glutathione

HD:

Huntington’s disease

HIF-1α:

Hypoxia-inducible factor-1α

HO-1:

Heme oxygenase 1

HT22:

Mouse hippocampal neuronal cells

iPSC:

Induced pluripotent stem cell

IS:

Ischemic stroke

MMP-9:

Metalloprotein-9

MS:

Multiple sclerosis

MSC:

Mesenchymal stem cell

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor kappa B

NPC:

Neural stem/precursor cell

Nrf2:

Nuclear factor erythroid 2‐related factor 2

OAC:

Oleanolic acid

PD:

Parkinson’s disease

PHF:

Paired helical filaments

PI3K:

Phosphatidylinositol 3-kinase

PNS:

Peripheral nervous system

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

SIRT1:

Member of sirtuin family

STAT:

Signal transducers and activators of transcription

TBI:

Traumatic brain injury

TERC:

Telomerase RNA subunit

TERT:

Telomerase catalytic subunit

TH:

Tyrosine hydroxylase

TL:

Telomere length

UC-MSC:

Umbilical cord-derived-MSC

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  1. Gülten Kuru and Göklem Üner have contributed equally to this work.

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  1. Department of Bioengineering, Faculty of Engineering, İzmir Institute of Technology, 35430, Urla, İzmir, Turkey

    Gülten Kuru, Göklem Üner & Erdal Bedir

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  1. Gülten Kuru
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Kuru, G., Üner, G. & Bedir, E. Is telomerase a hidden player? Therapeutic potential of natural telomerase activators against age-related diseases. Phytochem Rev 22, 35–72 (2023). https://doi.org/10.1007/s11101-022-09829-w

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