<i>Sirtuins</i>, a key regulator of ageing and age-related neurodegenerative diseases

Bhatt, Vidhi; Tiwari, Anjana

doi:10.1080/00207454.2022.2057849

Cited by 13 publications

(4 citation statements)

References 299 publications

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“…Studies have suggested a protective effect of sirtuins against a range of age‐related diseases such as cancer, diabetes, and NDs. SIRT1, especially, is implicated in processes including DNA repair, inhibition of inflammation, regulation of mitochondrial biogenesis, and stress resistance to ROS (Bernier et al., 2011 ; Bhatt & Tiwari, 2023 ; Brunet et al., 2004 ; Cohen et al., 2004 ; Liu et al., 2019 ). These age‐associated metabolic signaling pathways regulate not only nutrient sensing and response but also core aspects of stress response, cell survival, and inflammatory response.…”

Section: Age‐related Changes In the Human Bodymentioning

confidence: 99%

Microphysiological systems for human aging research

Park,

Laskow,

Chen

et al. 2024

Aging Cell

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Recent advances in microphysiological systems (MPS), also known as organs‐on‐a‐chip (OoC), enable the recapitulation of more complex organ and tissue functions on a smaller scale in vitro. MPS therefore provide the potential to better understand human diseases and physiology. To date, numerous MPS platforms have been developed for various tissues and organs, including the heart, liver, kidney, blood vessels, muscle, and adipose tissue. However, only a few studies have explored using MPS platforms to unravel the effects of aging on human physiology and the pathogenesis of age‐related diseases. Age is one of the risk factors for many diseases, and enormous interest has been devoted to aging research. As such, a human MPS aging model could provide a more predictive tool to understand the molecular and cellular mechanisms underlying human aging and age‐related diseases. These models can also be used to evaluate preclinical drugs for age‐related diseases and translate them into clinical settings. Here, we provide a review on the application of MPS in aging research. First, we offer an overview of the molecular, cellular, and physiological changes with age in several tissues or organs. Next, we discuss previous aging models and the current state of MPS for studying human aging and age‐related conditions. Lastly, we address the limitations of current MPS and present future directions on the potential of MPS platforms for human aging research.

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Section: Age‐related Changes In the Human Bodymentioning

confidence: 99%

Microphysiological systems for human aging research

Park,

Laskow,

Chen

et al. 2024

Aging Cell

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“…9,[35][36][37] The initial studies in neurodegeneration mouse models (Parkinson's disease and AD) suggested abnormal dysfunctional histone modifiers such as SIRT and HDAC family. 38,39 Further studies on heterochromatin protein 1α (HP1α), Polycomb group proteins, and ATP-dependent chromatin remodeler-like CHD5 indicated that the disrupted chromatin structures and organization contributed to aging and age-related neurodegenerative disorders. [40][41][42] Chromatin accessibility assays in bulk (ATAC-seq) showed that the AD-associated cis-regulatory domains were enriched in A compartments.…”

Section: Chromosomal Epigenome Erosion In Ad Brain Cell Typesmentioning

confidence: 99%

Epigenome erosion in Alzheimer’s disease brain cells and induced neurons

Wang,

Jones,

Zhou

et al. 2023

Preprint

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Late-onset Alzheimer's disease (LOAD) is typically sporadic, correlated only to advanced age, and has no clear genetic risk factors. The sporadic nature of LOAD presents a challenge to understanding its pathogenesis and mechanisms. Here, we comprehensively investigated the epigenome of LOAD primary entorhinal cortex brain tissues via single-cell multi-omics technologies, simultaneously capturing DNA methylation and 3D chromatin conformation. We identified AD-specific DNA methylation signatures and found they interact with bivalent promoters of AD differentially expressed genes. In addition, we discovered global chromosomal epigenome erosion of 3D genome structure within and across brain cell types. Furthermore, to evaluate whether these age- and disease-dependent molecular signatures could be detected in the in vitro cellular models, we derived induced neurons (iNs) converted directly from AD patients' fibroblasts and found a set of conserved methylation signatures and shared molecular processes. We developed a machine-learning algorithm to identify robust and consistent methylation signatures of LOAD in vivo primary brain tissues and in vitro fibroblast-derived iNs. The results recapitulate the age- and disease-related epigenetic features in iNs and highlight the power of epigenome and chromatin conformation for identifying molecular mechanisms of neuronal aging and generating biomarkers for LOAD.

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“…As recently reviewed, SIRTs are crucial, at different molecular levels, for the regulation of neuronal cell death and the pathology of neurodegenerative diseases, like Alzheimer's and Parkinson's diseases, multiple sclerosis and amyotrophic lateral sclerosis (Manjula et al 2020, Bhatt & Tiwari 2022, Leite et al 2022. Several studies revealed that SIRT1 and 3 expression is reduced in the brain of patients with Alzheimer's disease (Lutz et al 2014, Yin et al 2018.…”

Section: Sirtuins In Neurological Diseasesmentioning

confidence: 99%

Sirtuins as potential therapeutic targets for mitigating OxInflammation in typical Rett syndrome: plausible mechanisms and evidence

Cordone

Pecorelli

Valacchi

2022

Redox Experimental Medicine

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Graphical abstract Abstract Rett syndrome (RTT), a monogenic neurodevelopmental disorder mainly affecting female, is caused by mutations in X-linked MECP2 gene, an ubiquitous epigenetic regulator. In addition to neurological issues, RTT patients show a variety of multisystem manifestations and impairment of different signalling and metabolic pathways, including compromised mitochondrial function, altered redox homeostasis, improper cholesterol metabolism and subclinical inflammation. The sirtuin family (SIRTs), comprising seven members, catalyses the NAD+-dependent deacetylation, ADP-ribosylation and deacylation of a wide range of targets and works as sensors of cellular energetic status. In addition, SIRTs can modulate activities and gene expression of proteins involved in cellular stress responses related to oxidative stress, mitochondrial dysfunctions and inflammation, in both physiological and pathological conditions. Given some shared molecular aspects, herein, we revised the current scientific literature and hypothesized the possible relationship of SIRTs signalling involvement in RTT pathogenesis and OxInflammation. Although further research is needed, uncovering the possible involvement of SIRTs in RTT could reveal new potential pharmacological targets for the disorder. In light of this, SIRT-enhancing compounds could likely represent a new option to be tested as co-adjuvant alternatives to the current therapies.

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Sirtuins, a key regulator of ageing and age-related neurodegenerative diseases

Cited by 13 publications

References 299 publications

Microphysiological systems for human aging research

Microphysiological systems for human aging research

Epigenome erosion in Alzheimer’s disease brain cells and induced neurons

Sirtuins as potential therapeutic targets for mitigating OxInflammation in typical Rett syndrome: plausible mechanisms and evidence

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