An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging

Kaur, Amanpreet; Macip, Salvador; Stover, Cordula M.

doi:10.3389/fcell.2020.00218

Cited by 22 publications

(15 citation statements)

References 88 publications

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“…Since several studies reported that synthetic senolytic chemical show side effect such as toxicity to normal cell despite the low effective concentration, the demand for natural substances that can offer similar effectiveness with fewer side effects is increasing [ 49 ]. Plant-derived compounds such as olive polyphenols, green tea catechins, resveratrol, fisetin has been reported to exert senolytic or senomorphic activity [ 50 ]. The effective concentration of these active compounds is less than 10 μg/mL while that of SMFE is 100–200 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

Senotherapeutic-like effect of Silybum marianum flower extract revealed on human skin cells

et al. 2021

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Cellular senescence causes irreversible growth arrest of cells. Prolonged accumulation of senescent cells in tissues leads to increased detrimental effects due to senescence associated secretory phenotype (SASP). Recent findings suggest that elimination of senescent cells has a beneficial effect on organismal aging and lifespan. In this study, using a validated replicative senescent human dermal fibroblasts (HDFs) model, we showed that elimination of senescent cells is possible through the activation of an apoptotic mechanism. We have shown in this replicative senescence model, that cell senescence is associated with DNA damage and cell cycle arrest (p21, p53 markers). We have shown that Silybum marianum flower extract (SMFE) is a safe and selective senolytic agent targeting only senescent cells. The elimination of the cells is induced through the activation of apoptotic pathway confirmed by annexin V/propidium iodide and caspase-3/PARP staining. Moreover, SMFE suppresses the expression of SASP factors such as IL-6 and MMP-1 in senescent HDFs. In a co-culture model of senescent and young fibroblasts, we demonstrated that senescent cells impaired the proliferative capacities of young cells. Interestingly, when the co-culture is treated with SMFE, the cell proliferation rate of young cells is increased due to the decrease of the senescent burden. Moreover, we demonstrated in vitro that senescent fibroblasts trigger senescent process in normal keratinocytes through a paracrine effect. Indeed, the conditioned medium of senescent HDFs treated with SMFE reduced the level of senescence-associated beta-galactosidase (SA-β-Gal), p16INK4A and SASP factors in keratinocytes compared with CM of senescent HDFs. These results indicate that SMFE can prevent premature aging due to senescence and even reprograms aged skin. Indeed, thanks to its senolytic and senomorphic properties SMFE is a candidate for anti-senescence strategies.

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Section: Discussionmentioning

confidence: 99%

Senotherapeutic-like effect of Silybum marianum flower extract revealed on human skin cells

et al. 2021

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“…Disruption of redox homeostasis due to prolonged exposure to oxidative stress (OS), manifested as reactive oxygen species (ROS)-mediated damage to biomolecules, has been identified as a crucial mediator for the progression of CS [ 5 – 9 ]. Although selective elimination of senescent cells (via senolytics) and prevention/slowed progression of senescence features (via senostatics) are attractive strategies, they also have undesirable adverse-effects such as high toxicity, low bioavailability, and chemical instability [ 10 – 12 ]. Therefore, the roles of biomolecules in maintenance of physiological homeostasis between OS and CS may provide novel strategies to promote healthy aging.…”

Section: Introductionmentioning

confidence: 99%

Differential role of melatonin in healthy brain aging: a systematic review and meta-analysis of the SAMP8 model

Sumsuzzman

Khan

Choi

et al. 2021

Aging

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The relationship between oxidative stress (OS) and cellular senescence (CS) is an important research topic because of the rapidly aging global population. Melatonin (MT) is associated with aging and plays a pivotal role in redox homeostasis, but its role in maintaining physiological stability in the brain (especially in OS-induced senescence) remains elusive. Here, we systematically reviewed the differential role of MT on OS-induced senescence in the SAMP8 mouse model. Major electronic databases were searched for relevant studies. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Overall, 10 studies met the inclusion criteria. MT treatment was associated with the reduction of lipid peroxidation (SMD = −2.00, 95% CI [−2.91, −1.10]; p < 0.0001) and carbonylated protein (MD = −5.74, 95% CI [−11.03, –0.44]; p = 0.03), and with enhancement of the reduced-glutathione/oxidized-glutathione ratio (MD = 1.12, 95% CI [0.77, 1.47]; p < 0.00001). No differences were found in catalase and superoxide dismutase activities between MT-treated and vehicle-treated groups. Furthermore, nuclear-factor-κB, cyclin-dependent kinase-5, and p53 were regulated by MT administration. MT may improve physiological stability during aging by regulating interactions in brain senescence, but acts differentially on the antioxidant system.

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“…Nonetheless, as these cells are important to normal homeostasis and physiology (99,101), their destruction comes at a fair cost. To illustrate the latter, the use of senolytics has been associated with reactivation of latent viral infections (242), systemic toxicity (243) and aberrant wound healing (244). Formal studies and clinical trials to assess their clinical efficacy are required prior to their consideration as therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

et al. 2021

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There is strong evidence that COVID-19 pathophysiology is mainly driven by a spatiotemporal immune deregulation. Both its phenotypic heterogeneity, spanning from asymptomatic to severe disease/death, and its associated mortality, are dictated by and linked to maladaptive innate and adaptive immune responses against SARS-CoV-2, the etiologic factor of the disease. Deregulated interferon and cytokine responses, with the contribution of immune and cellular stress-response mediators (like cellular senescence or uncontrolled inflammatory cell death), result in innate and adaptive immune system malfunction, endothelial activation and inflammation (endothelitis), as well as immunothrombosis (with enhanced platelet activation, NET production/release and complement hyper-activation). All these factors play key roles in the development of severe COVID-19. Interestingly, another consequence of this immune deregulation, is the production of autoantibodies and the subsequent development of autoimmune phenomena observed in some COVID-19 patients with severe disease. These new aspects of the disease that are now emerging (like autoimmunity and cellular senescence), could offer us new opportunities in the field of disease prevention and treatment. Simultaneously, lessons already learned from the immunobiology of COVID-19 could offer new insights, not only for this disease, but also for a variety of chronic inflammatory responses observed in autoimmune and (auto)inflammatory diseases.

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An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging

Cited by 22 publications

References 88 publications

Senotherapeutic-like effect of Silybum marianum flower extract revealed on human skin cells

Senotherapeutic-like effect of Silybum marianum flower extract revealed on human skin cells

Differential role of melatonin in healthy brain aging: a systematic review and meta-analysis of the SAMP8 model

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

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