Hallmarks of Aging in the Liver

Hunt, Nicholas J.; Kang, Sun Woo; Lockwood, Glen P.; Couteur, David G. Le; Cogger, Victoria C.

doi:10.1016/j.csbj.2019.07.021

Cited by 218 publications

(248 citation statements)

References 150 publications

(211 reference statements)

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“…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). Taken together, these data showed that multiple H2O2 treatments markedly induced premature senescence in AML12 cells [1].…”

Section: Senescence Induction and Validation In Aml12 Cellssupporting

confidence: 53%

“…Senescent cells secrete senescence-associated secretory proteins (SASP) such as IL6 and IL1b, and are thought to be responsible for creating a pro-inflammatory environment to neighbouring cells during aging-associated diseases [1,26,27]. We found that senescent AML12 cells showed higher expression of pro-inflammatory genes IL1b and IL6 (Figure 6a).…”

Section: Senescent Aml12 Cells Create a Pro-inflammatory Environmentmentioning

confidence: 95%

“…Senescent cells also had increased mitochondrial activity compared to control cells. However, this increased activity did not lead to more ATP production due to concomitant increases in basal uncoupling and proton leakage, which are hallmarks of senescent cells [1,25,27,29]. These findings thus explains the reason why there is increased AMP:ATP ratio leading to the AMPK activation often found in senescent cells [1,27,29].…”

Section: Senescent Cells Are Metabolically Hyperactive and Display Amentioning

confidence: 97%

“…Aging is a major risk factor for many chronic diseases. In the liver, aging increases the susceptibility towards acute liver injury and hepatic fibrotic response [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…Cellular senescence in the main feature manifested in tissues of the aging organism [1,[5][6][7][8]. It is characterized by permanent cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype [5].…”

Section: Introductionmentioning

confidence: 99%

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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.

show abstract

Section: Senescence Induction and Validation In Aml12 Cellssupporting

confidence: 53%

Section: Senescent Aml12 Cells Create a Pro-inflammatory Environmentmentioning

confidence: 95%

Section: Senescent Cells Are Metabolically Hyperactive and Display Amentioning

confidence: 97%

“…Aging is a major risk factor for many chronic diseases. In the liver, aging increases the susceptibility towards acute liver injury and hepatic fibrotic response [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Singh

Tripathi

Yen

et al. 2020

Preprint

View full text Add to dashboard Cite

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A glitch in the matrix: Age‐dependent changes in the extracellular matrix facilitate common sites of metastasis

Marino

Weeraratna

2020

Aging and Cancer

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People over 55 years old represent the majority of cancer patients and suffer from increased metastatic burden compared to the younger patient population. As the aging population increases globally, it is prudent to understand how the intrinsic aging process contributes to cancer progression. As we age, we incur aberrant changes in the extracellular matrix (ECM) of our organs, which contribute to numerous pathologies, including cancer. Notably, the lung, liver, and bone represent the most common sites of distal metastasis for all cancer types. In this review, we describe how age-dependent changes in the ECM of these organs influence cancer progression. Further, we outline how these alterations prime the premetastatic niche and why these may help explain the disparity in outcome for older cancer patients.

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Aging exaggerates acute‐on‐chronic alcohol‐induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1‐C/EBPα‐miRNA‐223 axis

Ren

Ding

et al. 2021

Hepatology

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Background and Aims: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and micro-RNA-223 (miR-223), and their contribution to ALD pathogeneses. Approach and Results: Young and aged myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR-223 expression were down-regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronicplus-binge ethanol-induced liver injury and inflammation and down-regulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, down-regulation of

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Hallmarks of Aging in the Liver

Cited by 218 publications

References 150 publications

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

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

A glitch in the matrix: Age‐dependent changes in the extracellular matrix facilitate common sites of metastasis

Aging exaggerates acute‐on‐chronic alcohol‐induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1‐C/EBPα‐miRNA‐223 axis

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