Senolytics: A Translational Bridge Between Cellular Senescence and Organismal Aging

Thoppil, Harikrishnan; Riabowol, Karl

doi:10.3389/fcell.2019.00367

Cited by 40 publications

(31 citation statements)

References 65 publications

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“…This might suggest that a more precise approach based on further research is required when selecting ingredients for synbiotic application in ageing. The application of senolytics, compounds that induce apoptosis in senescent cells, are currently undergoing clinical trials in humans for treating a variety of age-related pathologies [157,158]. Many senolytics, such as quercetin, fisetin, piperlongumine, and curcumin, have been identified as natural phytochemical compounds in foods [159].…”

Section: Synbioticsmentioning

confidence: 99%

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

et al. 2020

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Viral respiratory infections (VRIs) can spread quickly and cause enormous morbidity and mortality worldwide. These events pose serious threats to public health due to time lags in developing vaccines to activate the acquired immune system. The high variability of people’s symptomatic responses to viral infections, as illustrated in the current COVID-19 pandemic, indicates the potential to moderate the severity of morbidity from VRIs. Growing evidence supports roles for probiotic bacteria (PB) and prebiotic dietary fiber (DF) and other plant nutritional bioactives in modulating immune functions. While human studies help to understand the epidemiology and immunopathology of VRIs, the chaotic nature of viral transmissions makes it difficult to undertake mechanistic study where the pre-conditioning of the metabolic and immune system could be beneficial. However, recent experimental studies have significantly enhanced our understanding of how PB and DF, along with plant bioactives, can significantly modulate innate and acquired immunity responses to VRIs. Synbiotic combinations of PB and DF potentiate increased benefits primarily through augmenting the production of short-chain fatty acids (SCFAs) such as butyrate. These and specific plant polyphenolics help to regulate immune responses to both restrain VRIs and temper the neutrophil response that can lead to acute respiratory distress syndrome (ARDS). This review highlights the current understanding of the potential impact of targeted nutritional strategies in setting a balanced immune tone for viral clearance and reinforcing homeostasis. This knowledge may guide the development of public health tactics and the application of functional foods with PB and DF components as a nutritional approach to support countering VRI morbidity.

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Section: Synbioticsmentioning

confidence: 99%

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

et al. 2020

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“…Moreover, the mRNA expression of senescence marker genes, P53, P21 and P16 were increased in the senescent AML12 cells compared to control AML12 cells (Figure 1d). Similarly, the expression of these genes also was increased in livers from old mice (100-108 week age) compared to those from young mice (12)(13)(14)(15)(16)(17)(18)(19)(20) week age) (Figure 1e). Furthermore, multiple H2O2 treatments increased senescence since there was increased activated -Gal (SA -Gal)-positive cells (Figure 2a,b) and H2A.X-positive cells containing condensed chromatin in larger nuclei (Figure 2c,d).…”

Section: Senescence Induction and Validation In Aml12 Cellsmentioning

confidence: 82%

“…In this regard, senescent AML12 cells would be useful to identify SASPs and understand their roles in causing inflammation in hepatic cells. These cells also could be useful for understanding the pathological molecular and metabolic changes that occur in age-related chronic hepatic diseases such as NASH, hepatic cirrhosis, and HCC, as well as for screening nutraceuticals and pharmaceuticals that might be useful to treat the pathological features associated with aging and senescence, and their associated metabolic conditions [4,16,17,48,49,51,52].…”

Section: Senescent Cells Are Metabolically Hyperactive and Display A mentioning

confidence: 99%

“…Under pathological stress conditions, excessive accumulation of senescence cells in affected tissues adversely affects the tissue's regenerative ability and creates a proinflammatory environment that can resemble various age-related disorders such as Alzheimer's disease, cancer, arthritis, cataracts, osteoporosis, atherosclerosis, hypertension, cardiovascular disease, Type 2 diabetes, and chronic liver disorders [3,5,7,[9][10][11][12]. Targeting senescent cells has the potential to delay age-associated disorders and/or reverse pathological metabolic phenotypes [3,[13][14][15][16]. Recent studies in the liver show that inducing hepatocyte senescence promotes fat accumulation and hepatic steatosis in vitro and in vivo [17].…”

Section: Introductionmentioning

confidence: 99%

“…However, these models have certain limitations as different cell types will react differently to a given stressor [23]. Furthermore, the method of senescence induction i.e., oxidative stress, gamma irradiation or overexpression of an oncogene, may contribute to variable phenotypes that may not necessarily resemble aging in vivo [5,16,23]. Thus, it is critical to verify the fidelity of in vitro models to tissues from aged mice.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development of an in vitro senescent hepatic cell model for metabolic studies in aging

Singh

Tripathi

Yen

et al. 2020

Preprint

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Although in vitro senescence models have been developed using primary fibroblasts, they may not be applicable for the study of metabolically active organs such as the liver. We thus developed an in vitro protocol to induce senescence in AML12 nontransformed hepatocyte cell lines derived from mice transgenic for transforming growth factor alpha. Sequential oxidative stress with hydrogen peroxide induced premature senescence in these cells as they exhibited molecular and metabolic signatures, had increased SA-Gal and H2A.X staining, and elevated senescence and pro-inflammatory gene expression that resembled the livers from aged mice.Metabolic phenotyping showed fuel switching towards more glycolysis, mitochondrial glutamine oxidation, and impaired energy production that also was similar to the livers from aged mice. Additionally, Senescence Activated Secretory Proteins (SASPs) sensitized normal AML12 cells to palmitate-induced toxicity, a known pathological effect of hepatic aging. In summary, we have generated an in vitro senescent AML12 cell model that not only show the molecular hallmarks of aging, but also recapitulates the aberrant metabolic phenotype found in aged liver. As such, they represent a novel and useful model to study nutritional, pharmacological, or genetic factors on hepatic metabolism during aging.

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Targeted Therapeutics Delivery by Exploiting Biophysical Properties of Senescent Cells

Low

Chan

Tay

2021

Adv Funct Materials

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Cellular senescence refers to a state of irreversible arrest of cell proliferation in response to various forms of cellular stress. It is known that the accumulation of senescent cells is a hallmark of aging, and mounting evidence has shown that the chronic accumulation of senescent cells is a significant contributor to various deleterious age-related pathologies. To limit the detrimental impacts of cellular senescence, there has been growing interest in targeted delivery of therapeutics to senescent cells to treat age-related pathologies and promote healthy aging. Two popular strategies include the elimination of senescent cells using senolytic drugs, and rejuvenation of senescent cells. To that end, it is integral that the delivery of senolytics, senomorphics or rejuvenating biomolecules to senescent cells are highly selective to enhance delivery efficacy and safety. However, there is little understanding of how senescence-associated biophysical changes such as cellular size and stiffness can be exploited for targeted therapeutics delivery. In this review, the biomolecular and biophysical markers of senescence along with senescence models and emerging therapeutics are first described. This review then focuses on how biophysical properties can be exploited for targeted therapeutics delivery, using approaches like nanoparticles, electroporation, sonoporation, photoporation and high aspect-ratio nanostructures to senescent cells.

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Senolytics: A Translational Bridge Between Cellular Senescence and Organismal Aging

Cited by 40 publications

References 65 publications

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

Development of an in vitro senescent hepatic cell model for metabolic studies in aging

Targeted Therapeutics Delivery by Exploiting Biophysical Properties of Senescent Cells

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