Sexual Dimorphic Metabolic and Cognitive Responses of C57BL/6 Mice to Fisetin or Dasatinib and Quercetin Cocktail Oral Treatment

Fang, Yimin; Medina, David; Stockwell, Robert; McFadden, Samuel; Quinn, Kathleen; Peck, Mackenzie R; Bartke, Andrzej; Hascup, Kevin N.; Hascup, Erin R.

doi:10.1101/2021.11.08.467509

Cited by 7 publications

(18 citation statements)

References 54 publications

(97 reference statements)

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“…Overall, the sex‐specificity observed in our results may be due to the sex‐specific effects of quercetin as a senolytic drug itself (40). Other studies have also demonstrated that dasatinib combined with quercetin can improve the cognitive ability of aged male Wistar rats, reflecting sex‐specific neuroprotective effects (41).…”

Section: Discussionmentioning

confidence: 68%

Senolytic Drug Quercetin Rescues Survival from Blue Light Toxicity in Drosophila Model

Zhang

Shan

Liang

et al. 2022

Photochem & Photobiology

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With the increasing frequency of human exposure to blue light, the harmfulness of blue light has received wider attention. The damaging effect of blue light is complex and long‐lasting. In this study, Drosophila melanogaster was used as a model organism to investigate the protective effect of the senolytic drug quercetin on blue light toxicity. As one of the first senolytic drugs discovered, quercetin not only has antioxidant properties, but also has been used to treat various neurological disorders. Our study shows that quercetin can effectively prolong the survival of flies under blue light irradiation, and it significantly increases the egg production of female flies under blue light. In addition, after flies intaking quercetin under blue light, both the spontaneous activity and nutrient metabolism show significant sex‐specificity. The experimental results provide a potentially effective intervention method for organisms to defend against blue light toxicity, and reveal a new function of the senolytic drug quercetin from another perspective.

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Section: Discussionmentioning

confidence: 68%

Senolytic Drug Quercetin Rescues Survival from Blue Light Toxicity in Drosophila Model

Zhang

Shan

Liang

et al. 2022

Photochem & Photobiology

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“…However, a new study showed that fisetin or dasatinib and quercetin cocktail oral treatment had sexually dimorphic and chemical dependent effects on C57BL/6 mice [59]. When fisetin was given monthly to young adulthood mice (4-13 months), markers of aging reduced in males but not females.…”

Section: Plant Ingredients With Senolytic Activitymentioning

confidence: 99%

Dietary Phytochemicals that Can Extend Longevity by Regulation of Metabolism

Shen

Shan

Zhong

et al. 2022

Plant Foods Hum Nutr

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Diet provides energy and nutrition for human survival, and also provides various joy of taste. Extensive studies have shown that the major components of diet, such as protein, carbohydrate and fat, play important roles in regulating aging and longevity. Whether other dietary ingredients can help prevent aging and extend longevity is a very interesting question. Here based on recent findings, we discussed dietary plant ingredients that can extend longevity by regulation of metabolism, targeting TRP channels, mitophagy, senescence pathways and circadian rhythms. Better understanding of the detailed effects and mechanisms of dietary ingredients on longevity regulation, would be helpful for developing new intervention tools for preventing aging and aging related diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s11130-021-00946-z.

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“…For instance, the use of senolytics to remove senescent cells has shown success in males with adverse effects in females. Following treatment of a senolytic cocktail in C57BL/6 mice, male mice showed reduced SASP and improved cognitive performance using Morris water maze, while female mice showed exacerbated SASP and reduced cognitive performance using novel object recognition task ( Fang et al, 2022 ). Similar outcomes were also recently reported in C57BL/6 mice with rmTBI, where a reduction in senescence-related markers and improved spatial learning and memory were seen in treated males, but not females ( Schwab et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury

et al. 2023

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Emerging evidence suggests cellular senescence, as a consequence of excess DNA damage and deficient repair, to be a driver of brain dysfunction following repeated mild traumatic brain injury (rmTBI). This study aimed to further investigate the role of deficient DNA repair, specifically BRCA1-related repair, on DNA damage-induced senescence. BRCA1, a repair protein involved in maintaining genomic integrity with multiple roles in the central nervous system, was previously reported to be significantly downregulated in post-mortem brains with a history of rmTBI. Here we examined the effects of impaired BRCA1-related repair on DNA damage-induced senescence and outcomes 1-week post-rmTBI using mice with a heterozygous knockout for BRCA1 in a sex-segregated manner. Altered BRCA1 repair with rmTBI resulted in altered anxiety-related behaviours in males and females using elevated zero maze and contextual fear conditioning. Evaluating molecular markers associated with DNA damage signalling and senescence-related pathways revealed sex-specific differences attributed to BRCA1, where females exhibited elevated DNA damage, impaired DNA damage signalling, and dampened senescence onset compared to males. Overall, the results from this study highlight sex-specific consequences of aberrant DNA repair on outcomes post-injury, and further support a need to develop sex-specific treatments following rmTBI.

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Sexual Dimorphic Metabolic and Cognitive Responses of C57BL/6 Mice to Fisetin or Dasatinib and Quercetin Cocktail Oral Treatment

Cited by 7 publications

References 54 publications

Senolytic Drug Quercetin Rescues Survival from Blue Light Toxicity in Drosophila Model

Senolytic Drug Quercetin Rescues Survival from Blue Light Toxicity in Drosophila Model

Dietary Phytochemicals that Can Extend Longevity by Regulation of Metabolism

BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury

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