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Background: Coenzyme Q 10 (CoQ 10 ), also known as ubiquinone-10, is an important molecule of the mitochondrial respiratory chain that acts as an electron carrier between complexes I, II, and III and additionally functions as an antioxidant. Due to its bioenergetic properties, CoQ 10 is of high interest for therapeutic and cosmetic use. This study aims to characterize the metabolic impact of CoQ 10 on primary human dermal fibroblasts (HDF) using fluorescence lifetime imaging microscopy (FLIM) and electron microscopy., Methods: FLIM of nicotinamide adenine dinucleotide (NADH) is a robust method to characterize cellular energy metabolism that also provides spatial information. Electron microscopy offers a way to characterize the ultrastructure of mitochondria and reveal features not visible in FLIM., Results: We reported a shift towards longer lifetimes of NADH in primary fibroblasts from ten different donors upon treatment with CoQ 10 , which indicates the stimulation of oxidative phosphorylation. This is confirmed by phasor-based metabolic pattern segmentation, which showed localization of longer NADH lifetimes in CoQ 10 -treated cells, indicating activated mitochondria in the cytoplasm. In addition, a complementary investigation of the mitochondrial ultrastructure using transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography showed a reduction in stress granules in CoQ 10 -treated cells., Conclusions: Together, FLIM and electron microscopy (EM) imaging strongly imply that CoQ 10 stimulates cellular energy metabolism., (© 2024 The Author(s). Published by IMR Press.)

Background: Coenzyme Q10 (CoQ10) is a naturally produced, lipid-soluble molecule crucial for cellular energy production and antioxidant activity. It diminishes with age and under external stress factors in skin, leading to signs of aging. Beyond its role in cellular energy production within the mitochondria, CoQ10 is vital to skin's defense against oxidative stress, a key contributor to premature aging. Use of topical skincare products with CoQ10 can be effective to replenish levels of CoQ10 and reverse skin aging., Objective: This publication discusses the role of CoQ10 in skin aging along with the benefits of topical skincare products that incorporate CoQ10 as an ingredient., Methods: We searched the PubMed database using terms "Coenzyme Q10" and "skin" and "aging." Overall, the search yielded 80 results, but a limitation of 10 years was then applied to restrict publications to those with the most up-to-date science., Results: A total of 36 publications were identified and included as background for this article. These 36 publications encompassed both original research articles and review articles., Discussion: Applying topical skincare products with CoQ10 replenishes CoQ10 cellular levels, helping to normalize cellular energy homeostasis and providing antioxidative effects to support and repair cutaneous damage including signs of skin aging. In ex vivo and in vivo studies, application of CoQ10 increased CoQ10 levels both on the skin surface (i.e., stratum corneum) and even more in deeper levels of the skin. Clinically, topical application of CoQ10-formulated products reduces the depth of cutaneous wrinkles, a sign associated with aging., Conclusion: Aging and stressed skin are, in part, the result of alterations in cellular metabolic homeostasis, which can be reversed via the benefits of topical application of CoQ10-enriched formulations that stimulate cutaneous energy metabolism and reduce free radicals via antioxidant function. By restoring physiological homeostasis, topical skincare products with CoQ10 replenish the skin's antioxidant levels, increase cellular (energy) metabolism, and reduce the signs of skin aging., Competing Interests: DISCLOSURES: Dr. Lain has served as consultant and/or investigator for AbbVie, Aclaris Therapeutics Inc., AlfaSigma, Allergan Inc., Almirall, Arcutis, AstraZeneca, Athenix, Biofrontera, Biopelle Inc., BioPharmX, Biorasi LLC, Bristol Myers Squibb, Brickell Biotech Inc., Cassiopea S.p.A., Castle Biosciences, Celgene, Cellceutix, ChemoCentryx, Concert Pharma, Cutanea Life Sciences, Demira, Dermavant, Dermtech, Dow Pharmaceutical Sciences Inc., Dr Reddy’s Laboratory, Eli Lily, EPI Health, Endo Pharma, Evelo, Gage Development Company LLC, Galderma Laboratories, LP, Hovione, Incyte, Janssen, Johnson & Johnson, Kadmon Corporation LLC, La Roche-Posay Laboratorie Pharmaceutique, LEO Laboratories Ltd., Medimmune, Menlo Therapeutics, Mindera, Neothetics, Nielsen Holdings NV, Novartis, Ortho Dermatologics, Pierre Fabre, Pfizer Inc, Promius Pharma LLC, Sanofi, Sebacia Inc., Sienna Labs Inc., SkinCeuticals LLC, Sol-Gel Technologies, SUN Pharma, Symatese Timber Pharma, UCB, Valeant Pharmaceuticals North America LLC, and Vyne Therapeutics, and is a stockholder in Moleculin LLC; Agrawal, Ruvolo, and Dr. Weise are employees of Beiersdorf; Dr. Callender has served as an investigator and/or received grants from AbbVie/Allergan, Almirall, Aerolase, Arcutis, Avava, Beiersdorf, Eirion, Eli Lilly, Janssen, L’Oréal, Pfizer, Prollenium, Skinbetter Science, Symatese, Teoxane; as a consultant or advisor for Acne Store, Aerolase, Arcutis, Avita Medical, Beiersdorf, Cutera, Dermavant, EPI Health, Jeune Aesthetics, L’Oréal, OrthoDerm, Scientis, Sente, SkinCeuticals, UCB; as a speaker for Eli Lilly, L’Oréal, SkinCeuticals; and has received royalties from Elsevier and UpToDate., (Copyright © 2024. Matrix Medical Communications. All rights reserved.)

Objective: Advanced glycation end-products (AGEs) represent a large group of compounds generated by a non-enzymatic reaction between reducing sugars and amino groups. The formation and accumulation of AGEs in the skin lead to protein crosslinking, dermal stiffening and yellowing, which ultimately contribute to cutaneous ageing. Amino acids have been described to exhibit anti-glycation effects. The objective of this study was to understand the inhibitory role of the amino acid derivative N-acetyl-L-hydroxyproline (NAHP) as an anti-glycation active for human skin., Methods: A cell-free assay investigating the inhibition of glycation of serum albumin by NAHP was used to determine the capability of NAHP to decrease AGE formation. Also, by assessing the amount of the AGE N-(carboxymethyl)lysine (CML) the anti-glycation abilities of NAHP were investigated utilizing dot blot analysis. The improvement of cell-matrix interaction by NAHP was determined in vitro using a glycated fibroblast-populated collagen lattice (FPCL) dermis model. In skin biopsies, AGE autofluorescence was determined after treatment with NAHP and/or glucose ex vivo., Results: NAHP significantly and dose-dependently inhibited levels of AGEs, which were induced by the glycation of a protein solution. This decrease could be visualized by showing that the brownish appearance as well as the AGE-specific fluorescence of glucose-treated samples were reduced after the application of increasing amounts of NAHP. Also, CML formation was dose-dependently inhibited by NAHP. In FPCLs, the contractile capacity of fibroblasts was significantly disturbed after glycation. This could be prevented by the addition of NAHP. Compared to glyoxal-treated samples, the co-application of NAHP significantly decreased the diameter as well as the weight of glycated FPCLs. Ex vivo application of glucose to skin explants showed a higher AGE fluorescence signal compared to control explants. Co-treatment with NAHP and glucose decreased the level of AGE fluorescence in comparison to glucose-treated explants., Conclusion: These data provide clear evidence that under glycation stress conditions treatment with NAHP inhibited AGE formation in vitro and ex vivo and prevented the loss of cellular contractile forces in a glycated dermis model. Thus, NAHP obviously provides a beneficial treatment option to counteract AGE-related changes in human skin such as dermal stiffening and yellowish skin appearance., (© 2023 Beiersdorf AG. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Background: Hyaluronic acid (HA) is a unique molecule of the extracellular matrix with multiple biological activities. In skin, HA plays an essential role as a humectant, capable of binding up to 1,000 times its mass with water, providing skin with moisture and viscoelastic properties. HA concentration and synthesis decrease significantly in aging skin, due to exogenous and endogenous factors, including photoaging and HA metabolism. A key driver for HA degradation and reduced concentration is mediated via induction of reactive oxygen species (ROS) and other free radicals., Objective: In this study, we evaluate antioxidant ingredients essential in the development of next-generation HA-based topical formulations aimed at leveraging HA's ability to maximize anti-aging properties., Methods: Two antioxidants, glycine saponin ( Glycine soja germ extract) and glycyrrhetinic acid (enoxolone), were evaluated for stimulation of endogenous HA production and inhibition of endogenous hyaluronidase activity, respectively., Results: The antioxidant glycine saponin induced endogenous HA synthesis in fibroblasts, while the antioxidant glycyrrhetinic acid decreased the degradation rate of HA by 54 percent., Conclusion: While HA has been included in numerous topical skin products, critical aspects of HA metabolism, especially in aging skin, have often been overlooked, including decreases in HA synthesis with increasing age, and increases in HA degradation mediated by exogenously induced reactive oxygen species and free radicals and increased enzymatic degradation by endogenous hyaluronidases. Here, we describe a unique approach to inclusion of two antioxidants essential for the development of the next generation of antioxidant complex-based topical skin formulations to limit the signs of aging skin., Competing Interests: DISCLOSURES: Dr. Zeichner has served as a consultant for Beiersdorf; Dr. Bussmann, Dr. Weiss, Ms. Maass, Ms. Krüger, Ms. Schade, and Mr. Kirchner are employees of Beiersdorf; Dr. Lain has served as a clinical trial investigator, consultant, advisor, and/or speaker for Beiersdorf, Pierre Fabre, L’Oreal, AbbVie, Galderma, Kenvue; Dr. Mariwalla has served as a consultant for Beiersdorf; Dr. Draelos has served as a trial investigator, consultant, advisor and/or speaker for Aveda, Beiersdorf, Estee Lauder, Galderma, La Roche Posay, L’Oreal, and SkinCeuticals., (Copyright © 2024. Matrix Medical Communications. All rights reserved.)

Excessive exposure to ultraviolet (UV) light leads to acute and chronic UV damage and is the main risk factor for the development of skin cancer. In most countries with western lifestyle, the topical application of sunscreens on UV-exposed skin areas is by far the most frequently used preventive measure against sunburn. Further than preventing sunburns, increasing numbers of consumers are appreciating sunscreens with a medium- to high-level sun protective factor (SPF) as basis for sustainable-skin ageing or skin cancer prevention programs. However, recent investigations indicate that clinically significant DNA damages as well as a lasting impairment of cutaneous immunosurveillance already occur far below the standard of one minimal erythema dose (MED) sunburn level, which contributes to the current discussion of the clinical value of high-protective SPF values. Ex vivo investigations on human skin showed that the application of SPF30 reduces DNA damage for a day long sun exposure (24 MED) drastically by about 53% but is significantly surpassed by SPF100 reducing DNA damage by approx. 73%. Further analysis on different SPF protection levels in UV-exposed cell culture assays focusing on IL-18, cell vitality and cis/trans-urocanic acid support these findings. Whereas SPF30 and SPF50 + sunscreens already offer a solid UVB cover for most indications, our results indicate that SPF100 provides significant additional protection against mutagenic (non-apoptotic-) DNA damage and functional impairment of the cutaneous immunosurveillance and therefore qualifies as an optimized sunscreen for specifically vulnerable patient groups such as immunosuppressed patients, or skin cancer patients., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

The decline of mitochondrial function throughout the lifespan is directly linked to the development of ageing phenotypes of the skin. Here, we assessed alterations in markers of epidermal mitochondrial energy metabolism as a function of skin age. Human skin samples from distinct anatomical regions were obtained during routine dermatological surgery from 21 young (27.6 ± 1.71 year) and 22 old (76.2 ± 1.73 year) donors. Sections of skin samples were analysed by immunohistochemistry for mitochondrial subunits of each electron transport chain complex (I-V)/oxidative phosphorylation (OXPHOS), as well as proteins serving as a marker of mitochondrial mass (VDAC1) and the regulation of DNA transcription (TFAM). Staining intensities of ATP5F1A (comprising complex V) and TFAM in the epidermis of older subjects were significantly decreased compared with younger donors. Moreover, these effects were independent of UV exposure of the stained skin section. Overall, we demonstrate that ageing is associated with reduced protein levels of complex V of the mitochondrial respiratory chain and TFAM. These alterations may impair essential mitochondrial functions, exacerbating the cutaneous ageing process., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

X-ray fluorescence (XRF) imaging is a highly sensitive non-invasive imaging method for detection of small element quantities in objects, from human-sized scales down to single-cell organelles, using various X-ray beam sizes. Our aim was to investigate the cellular uptake and distribution of Q 10 , a highly conserved coenzyme with antioxidant and bioenergetic properties. Q 10 was labeled with iodine (I 2 -Q 10 ) and individual primary human skin cells were scanned with nano-focused beams. Distribution of I 2 -Q 10 molecules taken up inside the screened individual skin cells was measured, with a clear correlation between individual Q 10 uptake and cell size. Experiments revealed that labeling Q 10 with iodine causes no artificial side effects as a result of the labeling procedure itself, and thus is a perfect means of investigating bioavailability and distribution of Q 10 in cells. In summary, individual cellular Q 10 uptake was demonstrated by XRF, opening the path towards Q 10 multi-scale tracking for biodistribution studies.

Coenzyme Q 10 (CoQ 10 ) is an endogenous lipophilic quinone found in equilibrium between its oxidised (ubiquinone) and reduced (ubiquinol) form, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the ageing process. CoQ 10 biosynthesis decreases with age in different tissues including skin and its biosynthesis can be modulated by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins. Statin-induced CoQ 10 deprivation has previously been shown to be associated with the development of a senescence phenotype in cultured human dermal fibroblasts (HDF), hence this model was used to further investigate the role of CoQ 10 in skin ageing. The present study aimed to compare the bioavailability of exogenously added CoQ 10 , in the form of ubiquinone or ubiquinol, to CoQ 10 -deprived HDF, and to determine their efficacy in rescuing the senescent phenotype induced by CoQ 10 deprivation. First, additional senescence markers were implemented to further support the pro-ageing effect of statin-induced CoQ 10 deprivation in HDF. Indeed, numerous senescence-associated secretory phenotype (SASP) markers such as p21, IL-8, CXCL1, and MMP-1 were upregulated, whereas components of the extracellular matrix were downregulated (elastin, collagen type 1). Next, we showed that CoQ 10 supplementation to statin-treated HDF was able to counteract CoQ 10 deprivation and rescued the development of selected senescence/ageing markers in HDF. Ubiquinol resulted more bioavailable than ubiquinone at the same concentration (15 μg/mL) and it significantly improved the cellular oxidative status even within isolated mitochondria highlighting an effective subcellular delivery. Ubiquinol was also more efficient compared to ubiquinone in reverting the expression of the senescent phenotype, quantified in terms of β-galactosidase positivity, p21, collagen type 1, and elastin at the gene and protein expression levels. In conclusion, our results highlight the pivotal role of CoQ 10 for skin vitality and strongly support the use of both forms as a beneficial and effective anti-ageing skin care treatment., (Copyright © 2021. Published by Elsevier Inc.)

Coenzyme Q 10 (CoQ 10 ) is an endogenous lipophilic quinone, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the aging process. In fact, coenzyme Q 10 synthesis is known to decrease with age in different tissues including skin. Moreover, synthesis can be inhibited by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins, that are widely used hypocholesterolemic drugs. They target a key enzymatic step along the mevalonate pathway, involved in the synthesis of both cholesterol and isoprenylated compounds including CoQ 10 .In the present study, we show that pharmacological CoQ 10 deprivation at concentrations of statins > 10000 nM triggers intracellular oxidative stress, mitochondrial dysfunction and generates cell death in human dermal fibroblasts (HDF). On the contrary, at lower statin concentrations, cells and mainly mitochondria, are able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. Importantly, our data demonstrate that CoQ 10 decrease promotes mitochondrial permeability transition and bioenergetic dysfunction leading to premature aging of human dermal fibroblasts in vitro .

Background: Periostin is a secreted 90kDa matricellular protein, which is predominantly expressed in collagen-rich tissues. Collagen is the most abundant protein in mammals and has great tensile strength. Recent investigations have shown that periostin influences collagen fibrillogenesis and biomechanical properties of murine connective tissues., Objective: We investigated the function of periostin concerning collagen homeostasis during intrinsic and extrinsic skin aging. For this purpose, human skin samples of young and old donors as well as samples of photoaged and sun-protected skin areas were analyzed for periostin expression. Using in vitro models, we determined the cell types responsible for periostin expression and performed functional analyses with periostin knockdown cells., Methods: TaqMan Real-Time PCR, UV irradiation, knockdown experiments, immunostaining, electron microscopy, collagen degradation assay, collagen crosslink analysis., Results: Periostin expression is highest in the papillary dermis and downregulated during skin aging. Fibroblasts and non-follicular skin derived precursors were identified as main source for periostin expression in human skin. Periostin knockdown in fibroblasts has no effect on collagen expression, but results in an increased fibril diameter and aberrant collagen structure. This leads to an increased susceptibility of collagen toward proteases, whereas recombinant periostin protects collagen fibrils from degradation., Conclusion: Our data show that periostin plays an important role for proper collagen assembly and homeostasis. During skin aging periostin expression decreases and contributes to the phenotype of aged skin., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Telomerase is activated in the majority of invasive breast cancers, but the time point of telomerase activation during mammary carcinogenesis is not clear. We have recently presented a transgenic mouse model to study human telomerase reverse transcriptase (TERT) gene expression in vivo (hTERTp-lacZ). In the present study, hTERTp-lacZxWAP-T bitransgenic mice were generated to analyze the mechanisms responsible for human and mouse TERT upregulation during tumor progression in vivo. We found that telomerase activity and TERT expression were consistently upregulated in SV40-induced invasive mammary tumors compared to normal and hyperplastic tissues and ductal carcinoma in situ (DCIS). Human and mouse TERT genes are regulated similarly in the breast tissue, involving the CEBP transcription factors. Loss of CEBP-α and induction of CEBP-β expression correlated well with the activation of TERT expression in mouse mammary tumors. Transfection of CEBP-α into human or murine cells resulted in TERT repression, whereas knockdown of CEBP-α in primary human mammary epithelial cells resulted in reactivation of endogenous TERT expression and telomerase activity. Conversely, ectopic expression of CEBP-β activated endogenous TERT gene expression. Moreover, ChIP and EMSA experiments revealed binding of CEBP-α and CEBP-β to human TERT-promoter. This is the first evidence indicating that CEBP-α and CEBP-β are involved in TERT gene regulation during carcinogenesis., (Copyright © 2012 UICC.)

Background: Collagen is the most abundant protein in human skin and is responsible for its resilience. In particular during photoaging, collagen homeostasis is out of balance leading to a continuous loss of intact collagen and to the observed signs of aged skin such as diminished tensile strength and wrinkle development. The process of collagen turnover is very slow and the relevance of cellular uptake of damaged collagen, most likely mediated via Endo180 or integrin α2β1, still remains a matter of investigation., Objective: We investigated the role of different collagen receptors on dermal fibroblasts for collagen internalization and their impact on collagen homeostasis during photoaging., Methods: TaqMan Real-Time PCR, flow cytometry, UV irradiation, knockdown experiments and immunostaining., Results: We show that Endo180 and integrin α2 are regulated in photoaged skin and after acute UV stress in vivo and in vitro. Knockdown experiments revealed that Endo180 is essential for cellular uptake of collagen fragments by dermal fibroblasts, whereas integrin α2 is important for initial binding of collagen. UV irradiation decreases collagen endocytosis. This correlates with reduced Endo180 expression and pericellular accumulation of collagen fragments during photoaging., Conclusion: Our findings correlate for the first time impaired collagen uptake via Endo180 with the pericellular accumulation of collagen fragments during photoaging. We assume an altered pericellular niche of fibroblasts in photoaged skin that has an impact on collagen homeostasis., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Numerous studies have shown that extracellular matrix (ECM)-based scaffolds are suitable for dermal constructs for the differentiation of various cell types in vitro and for constructive tissue remodeling after implantation in vivo. However, a shortcoming of these ECM materials is its limited elastogenesis. Elastic fibers constitute an essential component of mammalian connective tissue and the presence of elastic fibers is crucial for the proper function of the cardiovascular, pulmonary, and intestinal systems. Since it is still largely unknown how cells coordinate the molecular events of elastic-fiber assembly, understanding the ability to regenerate elastic fibers in tissues remains a significant challenge. For this reason, human neonatal dermal fibroblasts (HDFneo) were analyzed for their potential to serve as a cell culture model for elastic fiber assembly. Using optical technologies such as multiphoton laser-scanning microscopy (MPSLM) we demonstrate that HDFneo stimulated with transforming growth factor β1 (TGF-β1) are able to produce a distinct and complex elastic fiber system in vitro. As shown by the desmosine and isodesmosine content, crosslinked elastic fibers were formed within the 3D ECM-based scaffold. This tissue-engineered dermal construct may prove to be an effective template for the development of medicinal approaches in regenerative soft skin tissue reconstruction through TGF-β1 induction., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The epidermis harbors adult stem cells that reside in the basal layer and ensure the continuous maintenance of tissue homeostasis. Various studies imply that stem cells generally possess specific defense mechanisms against several forms of exogenous stress factors. As sun exposition is the most prevalent impact on human skin, this feature would be of particular importance in terms of sensitivity to UV-induced DNA damage., Objective: To investigate whether human epidermal stem cells are susceptible to UV-induced DNA damage and subsequent functional impairment., Methods: A method to isolate human epidermal stem cells from suction blister epidermis was established and validated. Volunteers were treated with solar-simulated irradiation on test areas of the forearm and stem cells were isolated from suction blister material of this region. DNA damage was analyzed by staining for cyclobutane thymidine dimers. The functional consequences of UV-induced damages were assessed by colony forming efficiency assays and gene expression analyses., Results: Compared to an unirradiated control, stem cells isolated from areas that were exposed to solar-simulated radiation showed significantly more DNA lesions. Although the number of stem cells was not reduced by this treatment, a functional impairment of stem cells could be shown by reduced colony forming efficiency and altered gene expression of stem cell markers., Conclusions: Despite their essential role in skin maintenance, epidermal stem cells are sensitive to physiological doses of UV irradiation in vivo., (Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background & Aims: Telomerase activity has not been detected in healthy human liver biopsy samples, but it is up-regulated in most human liver tumors. It is not clear whether telomerase is activated in response to acute or chronic liver injury. Telomerase activity is closely associated with expression of its catalytic subunit, telomerase reverse transcriptase (TERT). We analyzed the activity of the human TERT (hTERT) promoter during liver regeneration in vivo and hepatocyte proliferation in vitro., Methods: We used hTERTp-lacZ transgenic mice, which contain an 8.0-kilobase pair fragment of the hTERT gene promoter, to study the role of TERT in liver regeneration following partial hepatectomy. As an in vitro model, we used the HepaRG cell line as a new model system for human hepatocyte proliferation and differentiation., Results: Activity of the hTERT promoter increased significantly after partial hepatectomy; it was also induced in hepatocytes, based on immunohistologic analysis. Similar to the in vivo results, telomerase activity and hTERT expression were up-regulated in proliferating HepaRG cells and repressed in response to growth arrest and differentiation. Promoter mapping revealed that a proximal 0.3-kilobase pair fragment contains all elements necessary for regulation of hTERT in HepaRG cells. We identified E2F2 and E2F7 as transcription factors that control the differential expression of hTERT in proliferating hepatocytes, in vitro and in vivo., Conclusions: hTERT is induced in hepatocytes during liver regeneration, indicating a functional role for telomerase in human liver., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In adult testis, telomerase activity is exclusively detectable during the early steps of spermatogenesis and is downregulated during differentiation to spermatozoa. Knowledge about telomerase activity during testis development from birth to adulthood is still scarce. Telomerase activity is regulated primarily via the transcriptional initiation of TERT expression which encodes its catalytic subunit. We used the hTERTp-lacZ transgenic mouse model that expresses the bacterial lacZ reporter gene under the control of an 8.0-kbp human TERT promoter fragment to analyze simultaneously endogenous mouse Tert gene expression as well as human TERT promoter activity during mouse testis development. We show that human TERT promoter activity increased during puberty and was highest in adult mouse testis whereas mouse Tert expression and telomerase activity were found to be high in testis from the earliest time point tested (6 days postpartum). Histological analysis revealed that beta-galactosidase expression, encoded by the lacZ reporter gene, is present in all seminiferous tubules in adult testis, but in a subset of tubules before puberty. We further analyzed the expression of SCF/ c-KIT, which was described to regulate spermatogonia proliferation and mouse Tert expression, in prepubertal and adult testis by immunohistochemistry. Whereas SCF and c-KIT were detectable in all seminiferous tubules, a spatial and preclusive expression pattern of human TERT promoter activity and activated c-KIT (p-c-KIT Tyr 567/569) was observed in prepubertal testes.

Since the discovery that telomerase is repressed in most normal human somatic cells but strongly expressed in most human tumours, telomerase emerged as an attractive target for diagnostic, prognostic and therapeutic purposes to combat human cancer. In this review, a synopsis of methods detecting telomerase is presented evaluating their potential for diagnostic and prognostic use. Also, the most promising telomerase therapeutics are discussed in the light of recent advances in the field.