Epigenetic regulations in adult stem cells: the role of DNA methyltransferase in stem cell aging

Epigenomics ◽  
2011 ◽  
Vol 3 (6) ◽  
pp. 671-673 ◽  
Author(s):  
Kyung-Sun Kang
2011 ◽  
Vol 193 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Ling Liu ◽  
Thomas A. Rando

Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases.


Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.


2011 ◽  
pp. 35-55 ◽  
Author(s):  
Yoshiko Matsumoto ◽  
Hiroko Iwasaki ◽  
Toshio Suda

2020 ◽  
Vol 100 (1) ◽  
pp. 90-97
Author(s):  
R.L. Yang ◽  
H.M. Huang ◽  
C.S. Han ◽  
S.J. Cui ◽  
Y.K. Zhou ◽  
...  

To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism–related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen–positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.


2019 ◽  
Vol 98 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Nagarajan Maharajan ◽  
Karthikeyan Vijayakumar ◽  
Chul Ho Jang ◽  
Goang-Won Cho

Author(s):  
Shanshan Chen ◽  
Wenqi Wang ◽  
Hor-Yue Tan ◽  
Yuanjun Lu ◽  
Zhiping Li ◽  
...  

Autophagy is an intracellular scavenging mechanism induced to eliminate damaged, denatured, or senescent macromolecular substances and organelles in the body. The regulation of autophagy plays essential roles in the processes of cellular homeostasis and senescence. Dysregulated autophagy is a common feature of several human diseases, including cancers and neurodegenerative disorders. The initiation and development of these disorders have been shown to be associated with the maintenance of disease-specific stem cell compartments. In this review, we summarize recent advances in our understanding of the role of autophagy in the maintenance of stemness. Specifically, we focus on the intersection between autophagy and adult stem cells in the initiation and progression of specific diseases. Accordingly, this review highlights the role of autophagy in stemness maintenance from the perspective of disease-associated mechanisms, which may be fundamental to our understanding of the pathogeneses of human diseases and the development of effective therapies.


Author(s):  
Sarah Karimi ◽  
Setareh Raoufi ◽  
Zohreh Bagher

Introduction: Aging is a natural phenomenon that is caused by changes in the cells of the body. Theoretically, aging starts from birth and lasts throughout life. These changes affect the function of the cells. Also, in old tissues, the capacity for homeostasis and tissue repair is decline due to destructive changes in specific tissue stem cells, niche of stem cells and systemic factors that regulate stem cell activity. Understanding molecular pathways that disrupt stem cell function during aging is crucial for the development of new treatments for aging-associated diseases. In this article, the symptoms of stem cell aging and the key molecular pathways that are commonly used for the aging of stem cells were discussed. We will consider experimental evidence for all of the mechanisms and evaluate the way that can slow down or even stop the aging process. Finally, we will look at the aging process of three types of stem cells.


2021 ◽  
pp. 495-518
Author(s):  
Shikha Sharma ◽  
Avinash Sanap ◽  
Kalpana Joshi ◽  
Ramesh Bhonde
Keyword(s):  

2018 ◽  
Vol 74 (9) ◽  
pp. 1396-1407 ◽  
Author(s):  
Mujib Ullah ◽  
Zhongjie Sun

Abstract Understanding the effect of molecular pathways involved in the age-dependent deterioration of stem cell function is critical for developing new therapies. The overexpression of Klotho (KL), an antiaging protein, causes treated animal models to enjoy extended life spans. Now, the question stands: Does KL deficiency accelerate stem cell aging and telomere shortening? If so, what are the specific mechanisms by which it does this, and is cycloastragenol (CAG) treatment enough to restore telomerase activity in aged stem cells? We found that KL deficiency diminished telomerase activity by altering the expression of TERF1 and TERT, causing impaired differentiation potential, pluripotency, cellular senescence, and apoptosis in stem cells. Telomerase activity decreased with KL-siRNA knockdown. This suggests that both KL and telomeres regulate the stem cell aging process through telomerase subunits TERF1, POT1, and TERT using the TGFβ, Insulin, and Wnt signaling. These pathways can rejuvenate stem cell populations in a CD90-dependent mechanism. Stem cell dysfunctions were largely provoked by KL deficiency and telomere shortening, owing to altered expression of TERF1, TGFβ1, CD90, POT1, TERT, and basic fibroblast growth factor (bFGF). The CAG treatment partially rescued telomerase deterioration, suggesting that KL plays a critical role in life-extension by regulating telomere length and telomerase activity.


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