The role of cycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity

Yılmaz, Sinem; Bedіr, Erdal; Ballar, Petek

doi:10.1016/j.freeradbiomed.2022.06.230

Cited by 10 publications

(3 citation statements)

References 87 publications

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“…1999 ) and telomerase-related genes ( Ahmad et al. 2016 ; Yilmaz et al. 2022 and references therein).…”

Section: Discussionmentioning

confidence: 99%

Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

Romero-Haro,

Figuerola,

Alonso-Alvarez

2023

Integrative Organismal Biology

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Telomeres are repetitive DNA sequences at the end of chromosomes that protect them from degradation. They have been the focus of intense research because short telomeres would predict accelerated ageing and reduced longevity in vertebrates. Oxidative stress is considered a physiological driver of the telomere shortening and, consequently, short lifespan. Among molecules fighting against oxidative stress, glutathione is involved in many antioxidant pathways. Literature supports that oxidative stress may trigger a compensatory “hormetic” response increasing glutathione levels and telomere length. Here we tested the link between total glutathione concentration and telomere length in captive birds (zebra finches; Taeniopygia guttata). Total glutathione levels were experimentally decreased during birds’ growth using a specific inhibitor of glutathione synthesis (buthionine sulfoximine; BSO). We monitored the birds’ reproductive performance in an outdoor aviary during the first months of life, and their longevity for almost nine years. Among control individuals, erythrocyte glutathione levels during development positively predicted erythrocyte telomere length in adulthood. However, BSO-treated females, but not males, showed longer telomeres than control females in adulthood. This counterintuitive finding suggests that females mounted a compensatory response. Such compensation agrees with precedent findings in the same population where the BSO treatment increased growth and adult body mass in females but not males. BSO did not influence longevity or reproductive output in any sex. However, early glutathione levels and adult telomere length interactively predicted longevity only among control females. Those females with “naturally” low (non-manipulated) glutathione levels at the nestling age but capable of producing longer telomeres in adulthood seem to live longer. The results suggest that the capability to mount a hormetic response triggered by low early glutathione levels can improve fitness via telomere length. Overall, the results may indicate a sex-specific link between glutathione and telomere values. Telomerase activity and sexual steroids (estrogens) are good candidates to explain the sex-biased mechanism underlying the early-life impact of oxidative stress on adult telomere length.

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“…1999 ) and telomerase-related genes ( Ahmad et al. 2016 ; Yilmaz et al. 2022 and references therein).…”

Section: Discussionmentioning

confidence: 99%

Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

Romero-Haro,

Figuerola,

Alonso-Alvarez

2023

Integrative Organismal Biology

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“…Cycloastragenol is the only telomerase activator that has antiaging effects by increasing telomerase levels to delay telomere shortening (116,117). Astragaloside IV (AG-IV) has a variety of drug properties, such as anti-inflammatory, anti-IR and neuroprotective effects (118)(119)(120).…”

Section: Drug Therapy Of Diabetic Iddmentioning

confidence: 99%

From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration

Li,

Du,

Huang

et al. 2024

Front. Immunol.

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The incidence of lumbar disc herniation has gradually increased in recent years, and most patients have symptoms of low back pain and nerve compression, which brings a heavy burden to patients and society alike. Although the causes of disc herniation are complex, intervertebral disc degeneration (IDD) is considered to be the most common factor. The intervertebral disc (IVD) is composed of the upper and lower cartilage endplates, nucleus pulposus, and annulus fibrosus. Aging, abnormal mechanical stress load, and metabolic disorders can exacerbate the progression of IDD. Among them, high glucose and high-fat diets (HFD) can lead to fat accumulation, abnormal glucose metabolism, and inflammation, which are considered important factors affecting the homeostasis of IDD. Diabetes and advanced glycation end products (AGEs) accumulation- can lead to various adverse effects on the IVD, including cell senescence, apoptosis, pyroptosis, proliferation, and Extracellular matrix (ECM) degradation. While current research provides a fundamental basis for the treatment of high glucose-induced IDD patients. further exploration into the mechanisms of abnormal glucose metabolism affecting IDD and in the development of targeted drugs will provide the foundation for the effective treatment of these patients. We aimed to systematically review studies regarding the effects of hyperglycemia on the progress of IDD.

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“…The paper by Yao et al [22] uses panaxatriol saponin to ameliorate myocardial infarction-induced cardiac fibrosis in a NRF2/KEAP1 dependent manner. Yilmaz et al [23] report that cycloastragenol activates telomerase in a NRF2-dependent manner, suggesting an anti-ageing effect. Finally, Moreno et al [24], show that a biotinylated derivative of an acetylenic tricyclic bis(cyanoenone), but not its parent compound, exhibits bifunctional effects, activating NRF2 and inhibiting BACH1, a transcriptional repressor of a subset of NRF2-target genes.…”

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confidence: 99%

Introduction to Special Issue on “Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases”

Cuadrado

Dinkova‐Kostova

Mann

2023

Free Radical Biology and Medicine

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The role of cycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity

Cited by 10 publications

References 87 publications

Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?

From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration

Introduction to Special Issue on “Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases”

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