bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–09–24
seven papers selected by
Ayesh Seneviratne, Western University
  1. Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches.
  2. Long-term longitudinal analysis of 4,187 participants reveals new insights into determinants of incident clonal hematopoiesis.
  3. Past and Future Directions for Research on Cellular Senescence.
  4. Senescent cells at the crossroads of aging, disease, and tissue homeostasis.
  5. Mitochondrial protein and organelle quality control-Lessons from budding yeast.
  6. Prescription for a healthy diet.
  7. Aging adipose tissue, insulin resistance, and type 2 diabetes.
  1. Free Radic Biol Med. 2023 Sep 20. pii: S0891-5849(23)00643-3. [Epub ahead of print]
    Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches.
    Cristina Mas-Bargues.
      Aging is a complex biological process characterized by a progressive decline in cellular and tissue function, ultimately leading to organismal aging. Stem cells, with their regenerative potential, play a crucial role in maintaining tissue homeostasis and repair throughout an organism's lifespan. Mitochondria, the powerhouses of the cell, have emerged as key players in the aging process, impacting stem cell function and contributing to age-related tissue dysfunction. Here are discuss the mechanisms through which mitochondria influence stem cell fate decisions, including energy production, metabolic regulation, ROS signalling, and epigenetic modifications. Therefore, this review highlights the role of mitochondria in driving stem cell senescence and the subsequent impact on tissue function, leading to overall organismal aging and age-related diseases. Finally, we explore potential anti-aging therapies targeting mitochondrial health and discuss their implications for promoting healthy aging. This comprehensive review sheds light on the critical interplay between mitochondrial function, stem cell senescence, and organismal aging, offering insights into potential strategies for attenuating age-related decline and promoting healthy longevity.
    Keywords:  Aging; Anti-aging therapies; Mitochondria; Senescence; Stem cells
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2023.09.019
  2. medRxiv. 2023 Sep 07. pii: 2023.09.05.23295093. [Epub ahead of print]
    Long-term longitudinal analysis of 4,187 participants reveals new insights into determinants of incident clonal hematopoiesis.
    Md Mesbah Uddin, Seyedmohammad Saadatagah, Abhishek Niroula, Bing Yu, Whitney Hornsby, Shriienidhie Ganesh, Kim Lannery, Art Shuermans, Michael C Honigberg, Alexander G Bick, Peter Libby, Benjamin L Ebert, Christie M Ballantyne, Pradeep Natarajan.
      Clonal hematopoiesis (CH), characterized by blood cells predominantly originating from a single mutated hematopoietic stem cell, is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CH is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CH. We found that age at baseline, sex, and dyslipidemia significantly influence the incidence of CH, while ASCVD and other traditional risk factors for ASCVD did not exhibit such associations. Our study also revealed associations between germline genetic variants and incident CH, prioritizing genes in CH development. Our comprehensive longitudinal assessment yields novel insights into the factors contributing to incident CH in older adults.
    DOI:  https://doi.org/10.1101/2023.09.05.23295093
  3. Cold Spring Harb Perspect Med. 2023 Sep 21. pii: a041205. [Epub ahead of print]
    Past and Future Directions for Research on Cellular Senescence.
    Yi Zhu, Zacharias P Anastasiadis, Jair Machado Espindola Netto, Tamara Evans, Tamar Tchkonia, James L Kirkland.
      Cellular senescence was initially described in the early 1960s by Hayflick and Moorehead. They noted sustained cell-cycle arrest after repeated subculturing of human primary cells. Over half a century later, cellular senescence has become recognized as one of the fundamental pillars of aging. Developing senotherapeutics, interventions that selectively eliminate or target senescent cells, has emerged as a key focus in health research. In this article, we note major milestones in cellular senescence research, discuss current challenges, and point to future directions for this rapidly growing field.
    DOI:  https://doi.org/10.1101/cshperspect.a041205
  4. Aging Cell. 2023 Sep 20. e13988
    Senescent cells at the crossroads of aging, disease, and tissue homeostasis.
    Chisaka Kuehnemann, Christopher D Wiley.
      Originally identified as an outcome of continuous culture of primary cells, cellular senescence has moved beyond the culture dish and is now a bona fide driver of aging and disease in animal models, and growing links to human disease. This cellular stress response consists of a stable proliferative arrest coupled to multiple phenotypic changes. Perhaps the most important of these is the senescence-associated secretory phenotype, or senescence-associated secretory phenotype -a complex and variable collection of secreted molecules release by senescent cells with a number of potent biological activities. Senescent cells appear in multiple age-associated conditions in humans and mice, and interventions that eliminate these cells can prevent or even reverse multiple diseases in mouse models. Here, we review salient aspects of senescent cells in the context of human disease and homeostasis. Senescent cells increase in abundance during several diseases that associated with premature aging. Conversely, senescent cells have a key role in beneficial processes such as development and wound healing, and thus can help maintain tissue homeostasis. Finally, we speculate on mechanisms by which deleterious aspects of senescent cells might be targeted while retaining homeostatic aspects in order to improve age-related outcomes.
    Keywords:  cellular senescence; disease drivers of aging; homeostasis; progeria; senolytics
    DOI:  https://doi.org/10.1111/acel.13988
  5. IUBMB Life. 2023 Sep 20.
    Mitochondrial protein and organelle quality control-Lessons from budding yeast.
    Emily Jie-Ning Yang, Pin-Chao Liao, Liza Pon.
      Mitochondria are essential for normal cellular function and have emerged as key aging determinants. Indeed, defects in mitochondrial function have been linked to cardiovascular, skeletal muscle and neurodegenerative diseases, premature aging, and age-linked diseases. Here, we describe mechanisms for mitochondrial protein and organelle quality control. These surveillance mechanisms mediate repair or degradation of damaged or mistargeted mitochondrial proteins, segregate mitochondria based on their functional state during asymmetric cell division, and modulate cellular fitness, the response to stress, and lifespan control in yeast and other eukaryotes.
    Keywords:  ageing; mitochondria; mitochondrial reactive oxygen species; oxidative stress; reactive oxygen species
    DOI:  https://doi.org/10.1002/iub.2783
  6. Nat Med. 2023 Sep 21.
    Prescription for a healthy diet.
    Karen O'Leary.
      
    Keywords:  Cardiovascular diseases; Nutrition; Obesity
    DOI:  https://doi.org/10.1038/d41591-023-00082-y
  7. Biogerontology. 2023 Sep 19.
    Aging adipose tissue, insulin resistance, and type 2 diabetes.
    Yixuan Zhao, Rensong Yue.
      With the increase of population aging, the prevalence of type 2 diabetes (T2D) is also rising. Aging affects the tissues and organs of the whole body, which is the result of various physiological and pathological processes. Adipose tissue has a high degree of plasticity and changes with aging. Aging changes the distribution of adipose tissue, affects adipogenesis, browning characteristics, inflammatory status and adipokine secretion, and increases lipotoxicity. These age-dependent changes in adipose tissue are an important cause of insulin resistance and T2D. Understanding adipose tissue changes can help promote healthy aging process. This review summarizes changes in adipose tissue ascribable to aging, with a focus on the role of aging adipose tissue in insulin resistance and T2D.
    Keywords:  Adipose tissue; Aging; Insulin resistance; Type 2 diabetes
    DOI:  https://doi.org/10.1007/s10522-023-10067-6
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