Regulation of Stem Cell Aging by Metabolism and Epigenetics

Ren, Rui; Ocampo, Alejandro; Liu, Guanghui; Belmonte, Juan Carlos Izpisúa

doi:10.1016/j.cmet.2017.07.019

Cited by 205 publications

(154 citation statements)

References 188 publications

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“…One striking hallmark of aging is altered stem cell behavior and, in some cases, stem cell exhaustion (López-Otín et al, 2013). In addition, there is increasing evidence that age-related changes in metabolism contribute to the age-associated decline in stem cell function (Ren et al, 2017). Lipid homeostasis is one of the metabolic parameters that are affected by aging.…”

Section: Aging and Degenerative Diseasesmentioning

confidence: 99%

Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot

Demarco

Jones

2020

Front. Cell Dev. Biol.

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Adult stem cells constitute an important reservoir of self-renewing progenitor cells and are crucial for maintaining tissue and organ homeostasis. The capacity of stem cells to self-renew or differentiate can be attributed to distinct metabolic states, and it is now becoming apparent that metabolism plays instructive roles in stem cell fate decisions. Lipids are an extremely vast class of biomolecules, with essential roles in energy homeostasis, membrane structure and signaling. Imbalances in lipid homeostasis can result in lipotoxicity, cell death and diseases, such as cardiovascular disease, insulin resistance and diabetes, autoimmune disorders and cancer. Therefore, understanding how lipid metabolism affects stem cell behavior offers promising perspectives for the development of novel approaches to control stem cell behavior either in vitro or in patients, by modulating lipid metabolic pathways pharmacologically or through diet. In this review, we will first address how recent progress in lipidomics has created new opportunities to uncover stem-cell specific lipidomes. In addition, genetic and/or pharmacological modulation of lipid metabolism have shown the involvement of specific pathways, such as fatty acid oxidation (FAO), in regulating adult stem cell behavior. We will describe and compare findings obtained in multiple stem cell models in order to provide an assessment on whether unique lipid metabolic pathways may commonly regulate stem cell behavior. We will then review characterized and potential molecular mechanisms through which lipids can affect stem cell-specific properties, including self-renewal, differentiation potential or interaction with the niche. Finally, we aim to summarize the current knowledge of how alterations in lipid homeostasis that occur as a consequence of changes in diet, aging or disease can impact stem cells and, consequently, tissue homeostasis and repair.

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Section: Aging and Degenerative Diseasesmentioning

confidence: 99%

Lipid Mediated Regulation of Adult Stem Cell Behavior

Clémot

Demarco

Jones

2020

Front. Cell Dev. Biol.

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“…Alpha-ketoglutaric acid (α-KG) is a known key co-factor for PHF8 and is essential for PHF8 to regulate expression of downstream target genes [26][27][28]. To investigate the mechanism underlying PHF8 activation associated with APOC2, we measured the level of α-KG in APOC2 overexpressing RKO cells and in APOC2 knockdown SW620 cells, as well as in the respective control cells.…”

Section: Apoc2 Activates Downstream Oncogenes By Modulating the Transmentioning

confidence: 99%

APOC2 accelerates colorectal cancer progression via modulating lipid metabolism and transcriptional activity of PHF8

Chen

Xiao

Wang

et al. 2019

Preprint

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The apolipoproteins (APOs) are the major proteins in blood lipid transportation.Emerging evidence has demonstrated that APOs might exert important function in tumor cells, but the underlying mechanism remains inclusive. In this study, we aim to explore the relationship between APOC2 dysfunction and colorectal cancer (CRC) malignancy. By analyzing the expression of APOC2 in 507 patients with CRC, we demonstrated that the APOC2 was overexpressed and associated with poor prognosis in CRC. We then found that high levels of APOC2 resulted in proliferation, invasion and metastasis of CRC cells in vitro and in vivo. Mechanistically, we revealed that APOC2 directly interacted with FASN which resulted in decreased levels of omega-3 fatty acids and increased levels of alpha-ketoglutarate (α-KG). Both RNA-seq and ChIP-seq analysis revealed that APOC2 overexpression resulted accumulation of α-KG leads to activation on the transcriptional program of PHF8 and thereby contributed to activation on genes involved in cell proliferation, invasion and metastasis. Together, our study unveiled the oncogenic role of APOC2 in tumor cells, which sheds new light on the potential of APOC2 as a biomarker in the prognosis of CRC.

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“…b) epigenetic changes such as histone modifications (eg acetylation, phosphorylation) 14 , methylation of DNA, non-coding RNAs, etc. 13 ; c) telomeres shortening, whereby the degree of telomeres shortening is in correlation with the risks of diseases associated with the aging 15 ; d) mitochondrial dysfunction resulting in changes in regulation of various signal processes 16 ; e) disturbance of clearance and degradation of damaged protein by proteasomes or autophagy 17 ; f ) derangement of pathways of nutrient recognition including factors such as IGF-1 (Insulin like growth factor-1), mTOR (mammalian target of rapamycin) and NAD-dependent sirtuins 18,19,20 ; g) stem cell exhaustion; h) reduced regeneration capacity during aging and in age-related diseases 21 ; i) changed intercellular communication 22 ; j) cellular senescence -one of the basic causes of aging and the most frequently observed hallmark of aging 23 .…”

Section: Halmarks Of Aging Processmentioning

confidence: 99%

Aging and senotherapeutics

Čepelak¹,

Dodig²

2019

Rad Hrvatske akademije znanosti i umjetnosti

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One of the key mechanisms of the aging process of an organism and of the dysfunctionality and chronic diseases related with aging is the so-called cell senescence. It implies irreversible cell cycle arrest that occurs in response to different forms of cellular stress. Senescent cells that accumulate over time are viable, subject to phenotypic changes and excrete different soluble factors, and may affect adjacent cells, resulting in tissue and organ function disorders. Since old age is an important risk factor for many diseases, the interest of the scientific community is to reduce or avoid the effects of the aging processes. Among numerous developed therapeutic strategies, the development of senotherapeutics (i.e. the targeting strategy) has a significant place and is based on the removal of senescent cells and the abolishment of their adverse effects. Although many questions are still open, based on numerous experimental studies, it is expected that the development of senotherapeutics will contribute to the healthy life of the elderly and the treatment of specific age-related diseases. Sažetak:Jedan od ključnih mehanizama procesa starenja organizma i sa starenjem povezanih disfunkcionalnosti i kroničnih bolesti je tzv. stanična senescencija (stanično starenje). Podrazumijeva nepovratni zastoj staničnog ciklusa koji se javlja kao odgovor na različite oblike staničnog stresa. Senescentne stanice koje se tijekom vremena akumuliraju, viabilne su , podliježu fenotipskim promjenama i izlučuju različite topljive čimbenike, te mogu utjecati na susjedne stanice, što rezultira poremećajem funkcije tkiva i organa. Kako je starosna dob bitan čimbenik rizika za brojne bolesti, ublažavanje ili izbjegavanje učinaka procesa starenja u fokusu je interesa znanstvene zajednice. Među brojnim terapijskim strategijama koje se razvijaju, značajno mjesto zauzima razvoj senoterapeutika, odnosno strategija ciljanja , odnosno ukljanjanja senescentnih stanica i poništavanja njihovih nepovoljnih učinaka. Premda su još uvijek otvorena brojna pitanja, temeljem brojnih eksperimentalnih istraživanja očekuje se da će razvoj senoterapeutika doprinijeti zdravom životnom vijeku starijih osoba kao i tretmanu specifičnih bolesti povezanih sa starenjem. ključne riječi: starenje; stanična senescencija; senoterapeutici OPEN ACCESS

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Regulation of Stem Cell Aging by Metabolism and Epigenetics

Cited by 205 publications

References 188 publications

Lipid Mediated Regulation of Adult Stem Cell Behavior

Lipid Mediated Regulation of Adult Stem Cell Behavior

APOC2 accelerates colorectal cancer progression via modulating lipid metabolism and transcriptional activity of PHF8

Aging and senotherapeutics

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