Novel roles for telomerase in aging

The effects of chronic sun exposure on skin are readily apparent when skin not typically exposed to the sun and skin regularly exposed to the sun are compared. While the sun is not the only aetiological factor in the dynamic process of skin ageing, it is the primary exogenous cause among several internal and environmental elements. Thus, photo-ageing, the main focus of this article, is a subset of extrinsic skin ageing. The influence of the sun in extrinsic skin ageing, as well as its role in potentially altering the normal course of intrinsic (also known as natural or cellular) ageing, is discussed. Telomeres, the specialized structures found at the ends of chromosomes, are believed to be integral to cellular ageing as well as in the development of cancer. The ageing process, both intrinsic and extrinsic, is also believed to be influenced by the formation of free radicals, also known as reactive oxygen species. The loss of collagen is considered the characteristic histological finding in aged skin. Wrinkling and pigmentary changes are directly associated with photo-ageing and are considered its most salient cutaneous manifestations. Such photodamage represents the cutaneous signs of premature ageing. In addition, deleterious consequences of chronic sun exposure, specifically various forms of photo-induced skin cancer, are also linked to acute and chronic sun exposure. The only known strategies aimed at preventing photo-ageing include sun avoidance, using sunscreens to block or reduce skin exposure to UV radiation, using retinoids to inhibit collagenase synthesis and to promote collagen production, and using anti-oxidants, particularly in combination, to reduce and neutralize free radicals.

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“…Intact telomeres are integral in extending the lifespan of cells [9]. With age, telomere length shortens.…”

Section: Intrinsic Ageingmentioning

confidence: 99%

Skin ageing and its treatment

Baumann¹

2007

The Journal of Pathology

531

477

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“…Besides its telomere-lengthening function, there is increasing evidence that TERT can have physiological roles that are independent of this central function in both mammals [11][12][13][14][15] and zebrafish 16 . Zebrafish telomerase promotes the development of haematopoietic cells through a non-canonical mechanism that is independent of the authentic telomerase activity of TERT and the role of this enzyme in telomere lengthening 16 .…”

mentioning

confidence: 99%

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

et al. 2014

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Dyskeratosis congenita (DC) is an inherited disorder with mutations affecting telomerase or telomeric proteins. DC patients usually die of bone marrow failure. Here we show that genetic depletion of the telomerase RNA component (TR) in the zebrafish results in impaired myelopoiesis, despite normal development of haematopoietic stem cells (HSCs). The neutropenia caused by TR depletion is independent of telomere length and telomerase activity. Genetic analysis shows that TR modulates the myeloid-erythroid fate decision by controlling the levels of the master myeloid and erythroid transcription factors spi1 and gata1, respectively. The alteration in spi1 and gata1 levels occurs through stimulation of gcsf and mcsf. Our model of TR deficiency in the zebrafish illuminates the non-canonical roles of TR, and could establish therapeutic targets for DC.

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“…This downregulation is thought to reduce the probability of tumor development (17). Telomerase is activated during the immune response and wound healing and is reactivated in approximately 85% of human tumors (4,19,21,35,58).…”

mentioning

confidence: 99%

Alternatively Spliced Telomerase Reverse Transcriptase Variants Lacking Telomerase Activity Stimulate Cell Proliferation

Hrdličková

Nehyba

Bose

2012

Molecular and Cellular Biology

113

138

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Eight human and six chicken novel alternatively spliced (AS) variants of telomerase reverse transcriptase (TERT) were identified, including a human variant (⌬4-13) containing an in-frame deletion which removed exons 4 through 13, encoding the catalytic domain of telomerase. This variant was expressed in telomerase-negative normal cells and tissues as well as in transformed telomerase-positive cell lines and cells which employ an alternative method to maintain telomere length. The overexpression of the ⌬4-13 variant significantly elevated the proliferation rates of several cell types without enhancing telomerase activity, while decreasing the endogenous expression of this variant by use of small interfering RNA (siRNA) technology reduced cell proliferation. The expression of the ⌬4-13 variant stimulated Wnt signaling. In chicken cells, AS TERT variants containing internal deletions or insertions that eliminated or reduced telomerase activity also enhanced cell proliferation. This is the first report that naturally occurring AS TERT variants which lack telomerase activity stimulate cell proliferation.

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Novel roles for telomerase in aging

Cited by 54 publications

References 40 publications

Skin ageing and its treatment

Skin ageing and its treatment

A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish

Alternatively Spliced Telomerase Reverse Transcriptase Variants Lacking Telomerase Activity Stimulate Cell Proliferation

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