bims-agimec 2024-10-27 papers

Issue of 2024–10–27
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

NPJ Aging. 2024 Oct 24. 10(1): 48

The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.

Nirmalya Dasgupta, Rouven Arnold, Anais Equey, Armin Gandhi, Peter D Adams.

Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells undergo epigenetic changes and how these alterations govern SASP expression.

DOI: https://doi.org/10.1038/s41514-024-00172-2

Ageing Res Rev. 2024 Oct 19. pii: S1568-1637(24)00367-2. [Epub ahead of print]102 102549

Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions.

Luigi Ferrucci, Flora Guerra, Cecilia Bucci, Emanuele Marzetti, Anna Picca.

Mitophagy is the intracellular recycling system that disposes damaged/inefficient mitochondria and allows biogenesis of new organelles to ensure mitochondrial quality is optimized. Dysfunctional mitophagy has been implicated in human aging and diseases. Multiple evolutionarily selected, redundant mechanisms of mitophagy have been identified, but their specific roles in human health and their potential exploitation as therapeutic targets are unclear. Recently, the characterization of the endosomal-lysosomal system has revealed additional mechanisms of mitophagy and mitochondrial quality control that operate via the production of mitochondria-derived vesicles (MDVs). Circulating MDVs can be isolated and characterized to provide an unprecedented opportunity to study this type of mitochondrial recycling in vivo and to relate it to human physiology and pathology. Defining the role of MDVs in human physiology, pathology, and aging is hampered by the lack of standardized methods to isolate, validate, and characterize these vesicles. Hence, some basic questions about MDVs remain unanswered. While MDVs are generated directly through the extrusion of mitochondrial membranes within the cell, a set of circulating extracellular vesicles leaking from the endosomal-lysosomal system and containing mitochondrial portions have also been identified and warrant investigation. Preliminary research indicates that MDV generation serves multiple biological roles and contributes to restoring cell homeostasis. However, studies have shown that MDVs may also be involved in pathological conditions. Therefore, further research is warranted to establish when/whether MDVs are supporting disease progression and/or are extracting damaged mitochondrial components to alleviate cellular oxidative burden and restore redox homeoastasis. This information will be relevant for exploiting these vesicles for therapeutic purpose. Herein, we provide an overview of preclinical and clinical studies on MDVs in aging and associated conditions and discuss the interplay between MDVs and some of the hallmarks of aging (mitophagy, inflammation, and proteostasis). We also outline open questions on MDV research that should be prioritized by future investigations.

Keywords: Exosomes; Extracellular vesicles; Inflammaging; Mitochondrial DNA; Mitochondrial quality control; Mitophagy

DOI: https://doi.org/10.1016/j.arr.2024.102549

NPJ Aging. 2024 Oct 21. 10(1): 46

Cell senescence in cardiometabolic diseases.

Mandy O J Grootaert.

Cellular senescence has been implicated in many age-related pathologies including atherosclerosis, heart failure, age-related cardiac remodeling, diabetic cardiomyopathy and the metabolic syndrome. Here, we will review the characteristics of senescent cells and their endogenous regulators, and summarize the metabolic stressors that induce cell senescence. We will discuss the evidence of cell senescence in the onset and progression of several cardiometabolic diseases and the therapeutic potential of anti-senescence therapies.

DOI: https://doi.org/10.1038/s41514-024-00170-4

Mol Cells. 2024 Oct 19. pii: S1016-8478(24)00162-6. [Epub ahead of print] 100137

Genetic and Epigenetic Alterations in Aging and Rejuvenation of Human.

Kyunghyuk Park, Min Chul Jeon, Dakyung Lee, Jong-Il Kim, Sun-Wha Im.

All the information essential for life is encoded within our genome and epigenome, which orchestrates diverse cellular states spatially and temporally. In particular, the epigenome interacts with internal and external stimuli, encoding and preserving cellular experiences, and it serves as the regulatory base of the transcriptome across diverse cell types. The emergence of single-cell transcriptomic and epigenomic data collection has revealed unique omics signatures in diverse tissues, highlighting cellular heterogeneity. Recent research has documented age-related epigenetic changes at the single-cell level, alongside the validation of cellular rejuvenation through partial reprogramming, which involves simultaneous epigenetic modifications. These dynamic shifts, primarily fueled by stem cell plasticity, have catalyzed significant interest and cross-disciplinary research endeavors. This review explores the genomic and epigenomic alterations with aging, elucidating their reciprocal interactions. Additionally, it seeks to discuss the evolving landscape of rejuvenation research, with a particular emphasis on dissecting stem cell behavior through the lens of single-cell analysis. Moreover, it proposes potential research methodologies for future studies.

Keywords: Aging; Cell differentiation; Cellular reprogramming; Cellular senescence; DNA damage; DNA repair; Double strand breaks; Epigenetics; Epigenomic instability; Genomic instability; Rejuvenation; Stem cell

DOI: https://doi.org/10.1016/j.mocell.2024.100137

J Transl Med. 2024 Oct 22. 22(1): 959

Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer.

Yicong Cheng, Yang Yang, Ling Bai, Jiuwei Cui.

The presence of microplastics within the human body has raised significant concerns about their potential health implications. Numerous studies have supported the hypothesis that the accumulation of microplastics can trigger inflammatory responses, disrupt the microbiome, and provoke immune reactions due to their physicochemical properties. Chronic inflammation, characterized by tissue damage, angiogenesis, and fibrosis, plays a crucial role in cancer development. It influences cancer progression by altering the tumor microenvironment and impairing immune surveillance, thus promoting tumorigenesis and metastasis. This review explores the fundamental properties and bioaccumulation of microplastics, as well as their potential role in the transition from chronic inflammation to carcinogenesis. Additionally, it provides a comprehensive overview of the associated alterations in signaling pathways, microbiota disturbances, and immune responses. Despite this, the current understanding of the toxicity and biological impacts of microplastics remains limited. To mitigate their harmful effects on human health, there is an urgent need to improve the detection and removal methods for microplastics, necessitating further research and elucidation.

Keywords: Chronic inflammation; Immune regulation; Microplastics; Oncogenesis; Tumor microenvironment

DOI: https://doi.org/10.1186/s12967-024-05731-5

Biochim Biophys Acta Mol Basis Dis. 2024 Oct 20. pii: S0925-4439(24)00541-6. [Epub ahead of print] 167547

Mitostasis in age-associated neurodegeneration.

Mrutyunjaya Panda, Maria Markaki, Nektarios Tavernarakis.

Mitochondria are essential organelles that play crucial roles in various metabolic and signalling pathways. Proper neuronal function is highly dependent on the health of these organelles. Of note, the intricate structure of neurons poses a critical challenge for the transport and distribution of mitochondria to specific energy-intensive domains, such as synapses and dendritic appendages. When faced with chronic metabolic challenges and bioenergetic deficits, neurons undergo degeneration. Unsurprisingly, disruption of mitostasis, the process of maintaining cellular mitochondrial content and function within physiological limits, has been implicated in the pathogenesis of several age-associated neurodegenerative disorders. Indeed, compromised integrity and metabolic activity of mitochondria is a principal hallmark of neurodegeneration. In this review, we survey recent findings elucidating the role of impaired mitochondrial homeostasis and metabolism in the onset and progression of age-related neurodegenerative disorders. We also discuss the importance of neuronal mitostasis, with an emphasis on the major mitochondrial homeostatic and metabolic pathways that contribute to the proper functioning of neurons. A comprehensive delineation of these pathways is crucial for the development of early diagnostic and intervention approaches against neurodegeneration.

Keywords: Age-associated neurodegenerative disorders; Metabolism; Mitochondria; Mitostasis; Neurodegeneration; Neurodegenerative diseases

DOI: https://doi.org/10.1016/j.bbadis.2024.167547

Biogerontology. 2024 Oct 23. 26(1): 1

The dynamic crosslinking between gut microbiota and inflammation during aging: reviewing the nutritional and hormetic approaches against dysbiosis and inflammaging.

Sakshi Chaudhary, Pardeep Kaur, Thokchom Arjun Singh, Kaniz Shahar Bano, Ashish Vyas, Alok Kumar Mishra, Prabhakar Singh, Mohammad Murtaza Mehdi.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.

Keywords: Aging; Gut microbiota; Homeostasis; Hormesis; Inflammation; Nutrition

DOI: https://doi.org/10.1007/s10522-024-10146-2