Breaking the aging epigenetic barrier

Sikder, Sweta; Arunkumar, Ganesan; Melters, Daniël P.; Dalal, Yamini

doi:10.3389/fcell.2022.943519

Cited by 5 publications

(5 citation statements)

References 162 publications

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“…The average human life expectancy has increased in recent times, and the burden of age-related diseases has increased along with it. A developing field of research is focused on the reversal of the aging phenotype via in vivo partial reprogramming through introducing Yamanaka factors ( Ocampo et al, 2016 ; Sikder et al, 2022 ). It is intriguing to see VSELs and Yamanaka factors at the crossroads of aging research, similar to making iPS cells.…”

Section: Discussionmentioning

confidence: 99%

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front “war” against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and “reprogram” into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the “light at the end of the tunnel.”

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Section: Discussionmentioning

confidence: 99%

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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“…A number of excellent articles concerned with chromatin changes during senescence have been published (Olan et al, 2020; Parry et al, 2018; Parry and Narita, 2016; Rocha et al, 2022; Sikder et al, 2022; Sławińska and Krupa, 2021; Swanson et al, 2015). These articles document both the similarities and differences observed comparing cellular senescence in different types of cells.…”

Section: Resultsmentioning

confidence: 99%

The Multifaceted Phenotype of Senescent HL-60/S4 Macrophages

Olins,

Mark Welch,

Saul

et al. 2024

Preprint

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Every cell has a multifaceted phenotype. Transcriptional analysis of functionally defined groups of genes can provide insight into this phenotypic complexity. In the present study, the mRNA transcriptome of phorbol ester (TPA) differentiated HL-60/S4 macrophage cells was scrutinized using Gene Set Enrichment Analysis (GSEA), which evaluates the strengths of various cellular phenotypes by examining the enrichment of functionally different gene sets. Employing GSEA, we obtained supporting evidence that HL-60/S4 macrophages are senescent, probably a consequence of enriched TGFβ and NOTCH signaling transcripts. There appears to be a reduction of transcripts for heterochromatin, nucleosome formation, and chromatin remodeling phenotypes. In addition, despite upregulated oxidative stress gene transcription, we observed a reduction of DNA damage and repair transcripts. GSEA indicated that transcripts for autophagy, extracellular matrix, and inflammation/inflammasomes are enriched. We also observed that the HL-60/S4 macrophage is enriched for apoptosis gene transcripts, which may promote necrotic death by pyroptosis. The long-term goal of this research direction is to see whether this complex multifaceted phenotypic pattern is shared with other types of macrophages and to determine what mechanisms might exist to coordinate these phenotypic facets within a single cell.

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“…[2][3][4][5][6] Aging is characterized by progressive changes and loss of cell function, and is an inexorable event faced by all organic organisms. [7] Most cancers were diagnosed over the age of 60. By the year of 2050, The World Health Organization estimated that over 20% of the global population will be over the age of 60.…”

Section: Introductionmentioning

confidence: 99%

“…During natural aging process, different aspects of cancer have been widely investigated, including individual accumulation of deleterious mutations, cancer-related immune surveillance, immunopathogenesis, immune therapy responses, genomic and epigenomic changes, and associated microbiota. [7,[9][10][11] A series of studies reported the aging microenvironment may have significant influence on tumor progression. [8,12,13] Significant studies that represent and reflect the key points and findings between the aging process and cancer genesis remain to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

A bibliometric study of the top 100 most cited papers on aging and cancer

Zhang

Guo

Zhang³

2023

Medicine

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Cancer has been the major and increasing cause of premature death and years of life lost. Various studies suggested the correlation between the aging process and cancer genesis. To evaluate the performance of the articles and to identify and compare the top-cited articles on aging and cancer, a cross-sectional bibliometric analysis was performed. Top-cited articles that were indexed in the Core databases in Web of Science were utilized to identify articles published from inception to September 3, 2022. The top 100 most-cited articles on aging and cancer were evaluated for their specific characteristics. Both Microsoft Office Excel and Visual Basic for Applications were used to analyze the number of publications and scientific cooperations among authors over time. The query identified the top 100 most-cited articles from the 368,504 articles. The top cited articles accumulated 308,106 citations. The citations per article ranged from 39,141 to 1040. Thirty journals published these 100 articles, with the Ca-A Cancer Journal for Clinicians publishing the largest number. Most articles have focused on the trend analysis of incidence, survival outcomes, and prognosis of cancer from different origins. Co-authorship analysis revealed intense collaborative activity between United States authoritative academic institutions and scholars. The present study is the first to analyze most cited papers in “aging and cancer.” The historical trends, current status, and future direction in the field of older patients with cancer are systematically summarized. The occurrence and development of cancer is correlated with aging.

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Breaking the aging epigenetic barrier

Cited by 5 publications

References 162 publications

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

The Multifaceted Phenotype of Senescent HL-60/S4 Macrophages

A bibliometric study of the top 100 most cited papers on aging and cancer

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