Divergent mechanisms of metabolic dysfunction drive fibroblast and T-cell senescence

Callender, Lauren A.; Carroll, Elizabeth C.; Bober, Emilia A.; Henson, Sian M.

doi:10.1016/j.arr.2018.06.001

Cited by 11 publications

(7 citation statements)

References 70 publications

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“…There is abundant evidence that the immunosenescence, e.g. the changes in T and B cells, is not identical to the senescence encountered in non-immune cells (Callender et al, 2018;Pawelec, 2019). It seems likely that the chronic pro-inflammatory condition of inflammaging remodels the immune system to prevent excessive inflammation with aging.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Activation of immunosuppressive network in the aging process

Salminen

2020

Ageing Research Reviews

114

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Activation of immunosuppressive network in the aging process

Salminen

2020

Ageing Research Reviews

114

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“…There is evidence that changes in surface markers of T cells, e.g., lack of CD28 expression, might cause an attrition of telomeres [ 210 , 211 ]. However, it seems that the markers of cellular senescence are not identical in fibroblasts and immune cells, although, for instance, CD8 + T and memory B cells can express the senescence-associated secretory phenotype (SASP), a common cellular marker of non-immune senescence [ 212 , 213 ]. Recently, Ong et al [ 214 ] identified a non-classical monocyte subset in elderly people which displayed a pro-inflammatory SASP phenotype as well as many other hallmarks of cellular senescence.…”

Section: Introductionmentioning

confidence: 99%

Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency

Salminen

Kaarniranta

Kauppinen

2019

Cell. Mol. Life Sci.

115

126

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The aging process is associated with chronic low-grade inflammation in both humans and rodents, commonly called inflammaging. At the same time, there is a gradual decline in the functional capacity of adaptive and innate immune systems, i.e., immunosenescence, a process not only linked to the aging process, but also encountered in several pathological conditions involving chronic inflammation. The hallmarks of immunosenescence include a decline in the numbers of naïve CD4 + and CD8 + T cells, an imbalance in the T cell subsets, and a decrease in T cell receptor (TCR) repertoire and signaling. Correspondingly, there is a decline in B cell lymphopoiesis and a reduction in antibody production. The age-related changes are not as profound in innate immunity as they are in adaptive immunity. However, there are distinct functional deficiencies in dendritic cells, natural killer cells, and monocytes/macrophages with aging. Interestingly, the immunosuppression induced by myeloid-derived suppressor cells (MDSC) in diverse inflammatory conditions also targets mainly the T and B cell compartments, i.e., inducing very similar alterations to those present in immunosenescence. Here, we will compare the immune profiles induced by immunosenescence and the MDSC-driven immunosuppression. Given that the appearance of MDSCs significantly increases with aging and MDSCs are the enhancers of other immunosuppressive cells, e.g., regulatory T cells (Tregs) and B cells (Bregs), it seems likely that MDSCs might remodel the immune system, thus preventing excessive inflammation with aging. We propose that MDSCs are potent inducers of immunosenescence.

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“…Cellular metabolism is essential for fibroblasts’ phenotype and function [ 34 ]. Previous research has suggested that despite the massive demand for oxygen in keloid fibroblasts, these cells do not rely on the oxidative metabolism but mainly on glycolysis for their ATP requirements [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM

Huang¹,

Han²,

Yan³

et al. 2023

IJMS

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Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.

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Divergent mechanisms of metabolic dysfunction drive fibroblast and T-cell senescence

Cited by 11 publications

References 70 publications

Activation of immunosuppressive network in the aging process

Activation of immunosuppressive network in the aging process

Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM

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