Mammalian Target of Rapamycin (mTOR), Aging, Neuroscience, and Their Association with Aging-Related Diseases

Celebi-Birand, Ergul Dilan; Karoğlu, Elif Tuğçe; Doldur-Balli, Fusun; Adams, Michelle M.

doi:10.1016/b978-0-12-802733-2.00007-4

Cited by 3 publications

(3 citation statements)

References 215 publications

(200 reference statements)

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“…It takes part in two distinct complexes, each with different structures and biological functions: the mammalian target of rapamycin complex 1 (mTORC1) and the mammalian target of rapamycin complex 2 (mTORC2). mTORC1 consists of mTOR, mLST8, DEPTOR, Raptor, AKT1S1/PRAS40 and possesses two main downstream effectors, p70 ribosomal S6 kinase (p70S6K) and the eukaryotic initiation factor 4E-binding protein (4E-BP), that regulate protein synthesis, cell cycle progression, and cell growth [49] by modulating the levels of key regulator proteins such as cyclin D1, which is essential for the promotion of G1/S cell cycle progression [50] (Figure 3). A growth factor binds the extracellular domain of a receptor tyrosine kinase at the cell membrane leading to its activation and autophosphorylation of tyrosine residues, which promotes recruitment of the amino-terminal domain of p85, the regulatory subunit of PI3K.…”

Section: Dis3l2 Knockdown Leads To Suppression Of the Mtor Signaling ...mentioning

confidence: 99%

DIS3L2: Unveiling a New Player in Tumorigenesis, with a Key Role in Colorectal Cancer

García-Moreno,

Matos,

Romão

2023

J Cell Signal

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DIS3L2 is a 3’-5’ exoribonuclease that recognizes and degrades uridylated transcripts in an exosome-independent manner and participates in several RNA degradation pathways, such as the nonsense-mediated mRNA decay, or the surveillance of aberrant structured non-coding RNAs. Although some studies have linked DIS3L2 to tumorigenesis and cancer-related processes, its exact role in the development and progression of cancer has remained unclear since the discovery of DIS3L2's ribonuclease activity a decade ago. While some authors have reported evidence of a tumor suppressor role for this exoribonuclease, other studies have shown DIS3L2 as a driver of tumorigenesis. Although differences in tissue type and methodologic approaches may somewhat account for the opposing findings, a recent study from our group further supports a pro-tumorigenic role for DIS3L2, this time in promoting colorectal cancer (CRC) progression. Indeed, proper DIS3L2 expression was proven essential to maintain key tumorigenic properties in CRC cells, including cell proliferation and invasion. Here, we summarize the current state of knowledge regarding the impact of DIS3L2 in cancer, namely in colorectal cancer. The collected data unveils DIS3L2 as a novel putative therapeutic target in cancer that warrants further investigation.

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Section: Dis3l2 Knockdown Leads To Suppression Of the Mtor Signaling ...mentioning

confidence: 99%

DIS3L2: Unveiling a New Player in Tumorigenesis, with a Key Role in Colorectal Cancer

García-Moreno,

Matos,

Romão

2023

J Cell Signal

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“…The mechanism related to this process and nutrient sensing pathways are believed to be intersecting with the mammalian target of rapamycin (mTOR) pathway, which is thought to be the target of regulation by CR. mTOR is a serine/threonine kinase that is named after its sensitivity to rapamycin, which directly inhibits mTOR activity and its downstream targets (Celebi-Birand et al, 2016). The nutrient deficiency that occurs during fasting or CR also inhibits the mTOR pathway.…”

Section: Deregulated Nutrient Sensing and Crmentioning

confidence: 99%

Effects of caloric restriction on the antagonistic and integrative hallmarks of aging

Erbaba

Arslan-Ergül

Adams

2021

Ageing Research Reviews

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Aging is a significant risk factor for cognitive decline associated with neurodegenerative diseases, which makes understanding what promotes 'healthy brain aging' very important. Studies suggest that caloric restriction (CR) is a non-genetic intervention that reliably extends life-and healthspan. Here, we review the CR literature related to both the subject of aging and alterations in cell cycle machinery, especially surrounding the regulation of the E2F/DP1 complex, to elucidate the cellular protection mechanisms in the brain induced via dietary applications. The alterations extending lifespan via CR appear to exert their effects by promoting survival of individual cells, downregulating cell proliferation, and inducing stem cell quiescence, which results in keeping the stem cell reserve for extreme needs. This survival instinct of cells is believed to cause some molecular adaptations for their maintenance of the system. Avoiding energy waste of proliferation machinery promotes the long term survival of the individual cells and this is due to adaptations to the limited nutrient supply in the environment. Such a protective mechanism induced by diet could be promoted via the downregulation of crucial cell cycle-related transcription activators. This review article aims to bring attention to the importance of molecular adaptations induced by diet that promote healthy brain aging. It will provide insights into alternative targets for new treatments or neuroprotective approaches against neurodegenerative pathophysiologies.

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“…Interestingly, many of the dermal ECM-related genes that are downregulated in aged human skin are regulated by the TGF-β pathway [9]. And many other pathways are also involved in skin aging, such as IGF-FOXO pathway, MAPK pathway, rapamycin (mTOR) pathway [10][11][12]. There are few literatures revealing the molecular mechanism of oligopeptides on skin aging.…”

Section: Introductionmentioning

confidence: 99%

Anti-wrinkle Effect of a Palmitoyl Oligopeptide Complex on Human Keratinocytes and Fibroblasts Through TGF-β1 Pathway

Lu¹,

Liu²,

Tian³

2020

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Many researchers revealed that dermal fibroblast which mainly synthesis the collagen and elastin in dermis were affects by skin ageing, such as the proliferation rate and gene expression level. Oligopeptides were verified by many reports on anti-aging focus on collagen synthesis, but few literatures revealed the molecular mechanism of oligopeptides on skin aging. The potential anti-ageing effect and the mechanism of PTC, a new palmitoyl oligopeptide complex, were evaluated. MTT assay was adopted to detect the anti-aging effect of PTC in both human dermal fibroblast HDF-a and keratinocyte NHEK. The mechanism of PTC was detected further by full transcriptome analysis using RNA-sequencing method, and ELISA analysis of key proteins. Skin wrinkles were measured by VC98 in vivo. PTC showed positive effect in cell proliferation and the biosynthesis of collagens, intergrins not only on fibroblasts, but also on keratinocytes. Moreover, many pathways were confirmed in the anti-aging effect of PTC, such as TGF-β1 pathway and ECM-receptor interaction. A cream contained 5.0% PTC showed significant improvement of skin wrinkles and roughness. So that, PTC has a potentially beneficial effect on the cell proliferation, the biosynthesis of ECM related proteins and the expression of many genes which are involved in cell cycle and secretory features to slow down skin aging. The molecular pathway maybe targets the TGF-β1 in both epidermis and dermis.

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Mammalian Target of Rapamycin (mTOR), Aging, Neuroscience, and Their Association with Aging-Related Diseases

Cited by 3 publications

References 215 publications

DIS3L2: Unveiling a New Player in Tumorigenesis, with a Key Role in Colorectal Cancer

DIS3L2: Unveiling a New Player in Tumorigenesis, with a Key Role in Colorectal Cancer

Effects of caloric restriction on the antagonistic and integrative hallmarks of aging

Anti-wrinkle Effect of a Palmitoyl Oligopeptide Complex on Human Keratinocytes and Fibroblasts Through TGF-β1 Pathway

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