Aspirin ameliorates the long‐term adverse effects of doxorubicin through suppression of cellular senescence

Feng, Mingxiao; Kim, Joohwee; Field, Kevin; Reid, Christine D.; Chatzistamou, Ioulia; Shim, Minsub

doi:10.1096/fba.2019-00041

Cited by 19 publications

(8 citation statements)

References 82 publications

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“…Recent evidence also suggests the role of metformin and acarbose in modulating the gut microbiome, thereby suppressing inflammation (Ahmadi et al, 2020; Smith et al, 2019). In addition to senolytics, metformin, rapamycin, MB, and aspirin have also been shown to lower senescence‐associated secretory phenotype (SASP) levels (Atamna et al, 2008; Feng et al, 2019; Moiseeva et al, 2013; Wang et al, 2017; Xiong et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

et al. 2022

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Common chronic diseases represent the greatest driver of rising healthcare costs, as well as declining function, independence, and quality of life. Geroscience-guided approaches seek to delay the onset and progression of multiple chronic conditions by targeting fundamental biological pathways of aging. This approach is more likely to improve overall health and function in old age than treating individual diseases, by addressing aging the largest and mostly ignored risk factor for the leading causes of morbidity in older adults. Nevertheless, challenges in repurposing existing and moving newly discovered interventions from the bench to clinical care have impeded the progress of this potentially transformational paradigm shift. In this article, we propose the creation of a standardized process for evaluating FDA-approved medications for their geroscience potential. Criteria for systematically evaluating the existing literature that spans from animal models to human studies will permit the prioritization of efforts and financial investments for translating geroscience and allow immediate progress on the design of the next Targeting Aging with MEtformin (TAME)-like study involving such candidate gerotherapeutics.

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Section: Resultsmentioning

confidence: 99%

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

et al. 2022

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“…Several novel drugs have been explored as senolytic, including Dasatinib (D), Quercetin (Q), D+Q [213], Luteolin [214], Fisetin [215,216], Navitoclax (ABT263) [217], BCL-XL inhibitors [216], HSP90 inhibitors [212] Piperlongumine [218], RG7112 [219], O-Vanillin [219], ABT-737 [220], and CD153 Vaccine [221] and aspirin [222,223], reviewed by Robbins et al recently [224] (Figure 2).…”

Section: Senolytics and Sasp Modulatorsmentioning

confidence: 99%

Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

Chandra

Rajawat

2021

IJMS

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Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis, which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in the bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Furthermore, we and others have shown that targeting cellular senescence pharmacologically was an effective tool to alleviate age- and radiation-induced osteoporosis. Senescent cells also have an altered secretome known as the senescence associated secretory phenotype (SASP), which may have autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton and how bone homeostasis is affected during age-related osteoporosis. The review has also discussed existing therapeutics for the treatment of osteoporosis and rationalizes for novel therapeutic options based on cellular senescence and the SASP as an underlying pathogenesis of an aging bone.

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“…Aspirin, consumed by around one-fifth of adults in the United States, has been associated with senolytic characteristics as well [ 163 , 164 ]. A 2019 randomized placebo-controlled trial assessed the impact of daily Aspirin consumption over 4–6 weeks in older adults.…”

Section: Interventionsmentioning

confidence: 99%

Young at Gut—Turning Back the Clock with the Gut Microbiome

et al. 2021

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Over the past century, we have witnessed an increase in life-expectancy due to public health measures; however, we have also seen an increase in susceptibility to chronic disease and frailty. Microbiome dysfunction may be linked to many of the conditions that increase in prevalence with age, including type 2 diabetes, cardiovascular disease, Alzheimer’s disease, and cancer, suggesting the need for further research on these connections. Moreover, because both non-modifiable (e.g., age, sex, genetics) and environmental (e.g., diet, infection) factors can influence the microbiome, there are vast opportunities for the use of interventions related to the microbiome to promote lifespan and healthspan in aging populations. To understand the mechanisms mediating many of the interventions discussed in this review, we also provide an overview of the gut microbiome’s relationships with the immune system, aging, and the brain. Importantly, we explore how inflammageing (low-grade chronic inflammation that often develops with age), systemic inflammation, and senescent cells may arise from and relate to the gut microbiome. Furthermore, we explore in detail the complex gut–brain axis and the evidence surrounding how gut dysbiosis may be implicated in several age-associated neurodegenerative diseases. We also examine current research on potential interventions for healthspan and lifespan as they relate to the changes taking place in the microbiome during aging; and we begin to explore how the reduction in senescent cells and senescence-associated secretory phenotype (SASP) interplay with the microbiome during the aging process and highlight avenues for further research in this area.

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Aspirin ameliorates the long‐term adverse effects of doxorubicin through suppression of cellular senescence

Cited by 19 publications

References 82 publications

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

Young at Gut—Turning Back the Clock with the Gut Microbiome

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