A Senescence-Centric View of Aging: Implications for Longevity and Disease

Borghesan, Michela; Hoogaars, Willem M.H.; Varela‐Eirin, Marta; Talma, Nynke; Demaria, Marco

doi:10.1016/j.tcb.2020.07.002

Cited by 168 publications

(154 citation statements)

References 139 publications

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“…Cellular senescence would also lead to abnormal expression of in ammatory cytokines and this phenomenon was de ned as SASP [25]. SASP was composed of a series of cytokines such as proin ammatory cytokines, growth factors, chemokines and matrix remodeling enzymes and these factors could cause chronic low-grade in ammation and accelerate the senescent progresses in both cells and organs [26]. More and more evidences show that the chronic low-grade in ammation was one of the most important manifestations of AMD [27].…”

Section: Discussionmentioning

confidence: 99%

Grape Seed Proanthocyanindin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway

Dai²,

Long

et al. 2021

Preprint

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Background: Cellular senescence of retinal pigment epithelium (RPE) cell was an important cause of degenerative retinal disorders, however, the potential effects of grape seed proanthocyanindin extract (GSPE) through regulating NAMPT/SIRT1/NLRP3 pathway remained unclear.Methods: The effects of GSPE on the cellular senescence biomarkers as well as NAMPT and NAD+ contents were detected in both in-vivo and in-vitro RPE cell models. The protection of GSPE treatment on the mitochondrial homeostasis and barrier function of RPE cells were detected with mtDNA lesions, JC-1 staining, ZO1 expression, trans-epithelial cell resistance (TEER) as well as senescence-associated secretory phenotype (SASP) expressions. The GSPE treatment with NAMPT inhibitor, Fk866, and SIRT1 inhibitor, EX-527, was used in the potential NAMPT/SIRT1/NLRP3 mechanism detection.Results: GSPE significantly improve the NAMPT and NAD+ content in aging mice and thus alleviated the RPE cellular senescence. In advanced in-vitro studies, GSPE could be an activator of NAMPT and thus relieved H2O2 induced NAD+ depression. In advanced analyses, it was reported that GSPE could alleviate mitochondrial homeostasis, barrier function and SASP of aging RPE cells. Thus, detection the SASP in in-vitro aging model provided us knowledge in the understanding of the anti-aging role of GSPE and following detailed pathological mechanism analyses demonstrated that GSPE demonstrated the protective effects in aging RPE cells through NAMPT/SIRT1/NLRP3 pathway.Conclusions: These findings indicate that GSPE alleviated cellular senescence both in-vivo and in-vitro through NAMPT/SIRT1/NLRP3 pathway. This study highlighted the importance both the potential GSPE in degenerative retinopathy as well as the crosstalk of NAD+ metabolism, SIRT1 function and NLRP3 activation.

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Section: Discussionmentioning

confidence: 99%

Grape Seed Proanthocyanindin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway

Dai²,

Long

et al. 2021

Preprint

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“…To temporarily stabilize and then eliminate overly damaged cells, we have cellular processes such as senescence. However, senescent cells accumulate within tissues during aging, in particular due to a decrease in their elimination by the immune system, and this accumulation incurs many age-related diseases [ 36 ]. Moreover, not only cells but also cell organelles can be damaged.…”

Section: Understanding the Aging Processmentioning

confidence: 99%

Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues

Alle

Milhavet

et al. 2021

IJMS

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Aging is associated with a progressive and functional decline of all tissues and a striking increase in many “age-related diseases”. Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. Here, we review emerging rejuvenation strategies that are based on reprogramming toward pluripotency. Some of these approaches may eventually lead to medical applications to improve healthspan and longevity.

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“…Emerging evidence indicates EVs as important mediators of SASP effects, capable of transmitting paracrine senescence to nearby cells by regulating cell proliferation, and inflammation (Takasugi, 2018;Borghesan et al, 2020). It was shown that when "young" murine BMSCs endocytosed EVs derived from aged marrow, this led to reduction of osteogenic differentiation and proliferation in "young" MSCs, increasing their senescence (Davis et al, 2017).…”

Section: Influence Of Pathophysiologic Environments On Msc-evsmentioning

confidence: 99%

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

Herrmann

Diederichs

Melnik

et al. 2021

Front. Bioeng. Biotechnol.

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The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies.

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A Senescence-Centric View of Aging: Implications for Longevity and Disease

Cited by 168 publications

References 139 publications

Grape Seed Proanthocyanindin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway

Grape Seed Proanthocyanindin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway

Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

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