The Use of Natural Agents to Counteract Telomere Shortening: Effects of a Multi-Component Extract of Astragalus mongholicus Bunge and Danazol

Guinobert, Isabelle; Blondeau, Claude; Colicchio, Bruno; Oudrhiri, Noufϊssa; Dieterlen, Alain; Jeandidier, Éric; Deschênes, Georges; Bardot, Valérie; Cotte, César; Ripoche, Isabelle; Carde, Patrice; Berthomier, Lucile; M’Kacher, Radhia

doi:10.3390/biomedicines8020031

Cited by 9 publications

(5 citation statements)

References 49 publications

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“…In addition, these data represent a first step in the establishment of the bridge between the genome and the chromosome [55], permitting better detection of chromosomal aberrations, and the introduction of this approach to the clinic, providing higher efficiency at a low cost. These data could help define potential therapeutic strategies including telomeres [56,57].…”

Section: Discussionmentioning

confidence: 96%

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

M’Kacher¹,

Colicchio

Borie

et al. 2020

Genes

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Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogenetics. We ascribe this discrepancy to the identification of the unique configuration of dicentric chromosomes. We observed significantly higher frequencies of telomere loss and deletion in patients with dicentric chromosomes (p < 10−4). TC+M-FISH analysis is superior to classical cytogenetics for the detection of chromosomal instability. Our approach is a relatively simple but useful tool for documenting telomere dysfunction and chromosomal instability with the potential to become a standard additional diagnostic tool in medical genetics and the clinic.

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Section: Discussionmentioning

confidence: 96%

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

M’Kacher¹,

Colicchio

Borie

et al. 2020

Genes

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“…Preventing and reversing cell aging and age-related changes in cells, tissues, and animals includes in vitro work in human cells [ 246 ], in vitro and ex vivo work in human tissues [ 81 , 247 , 248 ], and in vivo work in animals [ 61 , 249 ]. The promise of this approach is supported by data from various approaches inducing telomerase activity [ 62 , 250 , 251 , 252 , 253 , 254 ]. These include the use of TERT -activating compounds in acute coronary syndrome [ 255 ], whether via canonical or non-canonical effects [ 256 ].…”

Section: Perspective On Optimal Clinical Interventionmentioning

confidence: 99%

A Unified Model of Age-Related Cardiovascular Disease

Fossel

Bean

Khera

et al. 2022

Biology

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Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, affects all components of the cardiovascular system, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, cardiac fibroblasts, and immune cells. The unified model offers insights into the relationship between upstream risk factors and downstream clinical outcomes and explains why interventions aimed at either of these components have limited success. Potential therapeutic approaches are considered based on this model. Because telomerase activity can prevent and reverse cell senescence, telomerase gene therapy is discussed as a promising intervention. Telomerase gene therapy and similar systems interventions based on the unified model are expected to be transformational in cardiovascular medicine.

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“…A. membranaceus water extract can suppress cytokine production by inhibiting the NF-κB signaling pathway, alleviating inflammatory responses [ 20 ]. Ethanol extracts of Astragalus mongholicus roots induce significant telomere elongation in lymphocytes [ 21 ]. TA-65, a compound containing cycloastragenol isolated from A. membranaceus roots, has been shown to increase telomerase activity in embryonic fibroblasts, inhibit DNA damage, and enhance immune function [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Rosa roxburghii Fruit Extracts Upregulate Telomerase Activity and Ameliorate Cell Replicative Senescence

Huang,

Peng,

et al. 2024

Foods

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Anti-aging functional foods benefit the elderly. Telomeres are chromosomal ends that maintain genome stability extended by telomerase catalytic subunit TERT. Due to the end-replication problem, telomeres shorten after each cell cycle without telomerase in most human cells, and eventually the cell enters the senescence stage. Natural products can attenuate the aging process by increasing telomerase activity, such as TA-65. However, TA-65 is expensive. Other Chinese natural products may achieve comparable effects. Here, we found that Rosa roxburghii fruit extracts effectively increase TERT expression and telomerase activity in cultured human mesenchymal stem cells. Both R. roxburghii fruit extracts obtained by freeze-drying and spray-drying increased the activity of telomerase. R. roxburghii fruit extracts were able to reduce reactive oxygen species levels, enhance superoxide dismutase activity, and reduce DNA damage caused by oxidative stress or radiation. R. roxburghii fruit extracts promoted cell proliferation, improved senescent cell morphology, delayed replicative cellular senescence, attenuated cell cycle suppressors, and alleviated the senescence-associated secretory phenotype. Transcriptome and metabolic profiling revealed that R. roxburghii fruit extracts promote DNA replication and telomere maintenance pathways and decrease triglyceride levels. Overall, we provide a theoretical basis for the application of R. roxburghii fruit as an anti-aging product.

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The Use of Natural Agents to Counteract Telomere Shortening: Effects of a Multi-Component Extract of Astragalus mongholicus Bunge and Danazol

Cited by 9 publications

References 49 publications

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

A Unified Model of Age-Related Cardiovascular Disease

Rosa roxburghii Fruit Extracts Upregulate Telomerase Activity and Ameliorate Cell Replicative Senescence

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