bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–12–24
fiveteen papers selected by
Ayesh Seneviratne, Western University
  1. Epigenetic Mechanisms in Hematologic Aging and Premalignant Conditions.
  2. Exploring clonal hematopoiesis and its impact on aging, cancer, and patient care.
  3. Biomarkers of aging through the life course: A Recent Literature Update.
  4. The Information Theory of Aging.
  5. Age-Related Alternative Splicing: Driver or Passenger in the Aging Process?
  6. Age-related micro-environmental changes as drivers of clonal hematopoiesis.
  7. New anti-aging strategies: a narrative review.
  8. Editorial: The role of nutrition in healthy aging.
  9. The epigenetics of frailty.
  10. Cellular senescence and kidney aging.
  11. Muscle immune cells protect mitochondrial organelles during exercise.
  12. Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases.
  13. Microgravity Effects and Aging Physiology: Similar Changes or Common Mechanisms?
  14. Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.
  15. Inflammation in Heart Failure-Future Perspectives.
  1. Epigenomes. 2023 Dec 12. pii: 32. [Epub ahead of print]7(4):
    Epigenetic Mechanisms in Hematologic Aging and Premalignant Conditions.
    Bowen Yan, Qingchen Yuan, Olga A Guryanova.
      Hematopoietic stem cells (HSCs) are essential for maintaining overall health by continuously generating blood cells throughout an individual's lifespan. However, as individuals age, the hematopoietic system undergoes significant functional decline, rendering them more susceptible to age-related diseases. Growing research evidence has highlighted the critical role of epigenetic regulation in this age-associated decline. This review aims to provide an overview of the diverse epigenetic mechanisms involved in the regulation of normal HSCs during the aging process and their implications in aging-related diseases. Understanding the intricate interplay of epigenetic mechanisms that contribute to aging-related changes in the hematopoietic system holds great potential for the development of innovative strategies to delay the aging process. In fact, interventions targeting epigenetic modifications have shown promising outcomes in alleviating aging-related phenotypes and extending lifespan in various animal models. Small molecule-based therapies and reprogramming strategies enabling epigenetic rejuvenation have emerged as effective approaches for ameliorating or even reversing aging-related conditions. By acquiring a deeper understanding of these epigenetic mechanisms, it is anticipated that interventions can be devised to prevent or mitigate the rates of hematologic aging and associated diseases later in life. Ultimately, these advancements have the potential to improve overall health and enhance the quality of life in aging individuals.
    Keywords:  aging; epigenetics; hematopoietic stem cells
    DOI:  https://doi.org/10.3390/epigenomes7040032
  2. Aging (Albany NY). 2023 Dec 20. 15
    Exploring clonal hematopoiesis and its impact on aging, cancer, and patient care.
    Julieta Elena Rodriguez, Jean Baptiste Micol, Capucine Baldini.
      
    Keywords:  aging; clonal hematopoiesis; solid tumors
    DOI:  https://doi.org/10.18632/aging.205404
  3. Curr Opin Epidemiol Public Health. 2023 Jun;2(2): 7-17
    Biomarkers of aging through the life course: A Recent Literature Update.
    Abigail Gaylord, Alan Cohen, Allison Kupsco.
       Purpose of review: The development of biomarkers of aging has greatly advanced epidemiological studies of aging processes. However, much debate remains on the timing of aging onset and the causal relevance of these biomarkers. In this review, we discuss the most recent biomarkers of aging that have been applied across the life course.
    Recent findings: The most recently developed aging biomarkers that have been applied across the life course can be designated into three categories: epigenetic clocks, epigenetic markers of chronic inflammation, and mitochondrial DNA copy number. While these have been applied at different life stages, the development, validation, and application of these markers has been largely centered on populations of older adults. Few studies have examined trajectories of aging biomarkers across the life course. As the wealth of molecular and biochemical data increases, emerging biomarkers may be able to capture complex and system-specific aging processes. Recently developed biomarkers include novel epigenetic clocks; clocks based on ribosomal DNA, transcriptomic profiles, proteomics, metabolomics, and inflammatory markers; clonal hematopoiesis of indeterminate potential gene mutations; and multi-omics approaches.
    Summary: Attention should be placed on aging at early and middle life stages to better understand trajectories of aging biomarkers across the life course. Additionally, novel biomarkers will provide greater insight into aging processes. The specific mechanisms of aging reflected by these biomarkers should be considered when interpreting results.
    Keywords:  Aging; biomarkers; epigenetics; life course
    DOI:  https://doi.org/10.1097/pxh.0000000000000018
  4. Nat Aging. 2023 Dec;3(12): 1486-1499
    The Information Theory of Aging.
    Yuancheng Ryan Lu, Xiao Tian, David A Sinclair.
      Information storage and retrieval is essential for all life. In biology, information is primarily stored in two distinct ways: the genome, comprising nucleic acids, acts as a foundational blueprint and the epigenome, consisting of chemical modifications to DNA and histone proteins, regulates gene expression patterns and endows cells with specific identities and functions. Unlike the stable, digital nature of genetic information, epigenetic information is stored in a digital-analog format, susceptible to alterations induced by diverse environmental signals and cellular damage. The Information Theory of Aging (ITOA) states that the aging process is driven by the progressive loss of youthful epigenetic information, the retrieval of which via epigenetic reprogramming can improve the function of damaged and aged tissues by catalyzing age reversal.
    DOI:  https://doi.org/10.1038/s43587-023-00527-6
  5. Cells. 2023 Dec 12. pii: 2819. [Epub ahead of print]12(24):
    Age-Related Alternative Splicing: Driver or Passenger in the Aging Process?
    Marco Baralle, Maurizio Romano.
      Alternative splicing changes are closely linked to aging, though it remains unclear if they are drivers or effects. As organisms age, splicing patterns change, varying gene isoform levels and functions. These changes may contribute to aging alterations rather than just reflect declining RNA quality control. Three main splicing types-intron retention, cassette exons, and cryptic exons-play key roles in age-related complexity. These events modify protein domains and increase nonsense-mediated decay, shifting protein isoform levels and functions. This may potentially drive aging or serve as a biomarker. Fluctuations in splicing factor expression also occur with aging. Somatic mutations in splicing genes can also promote aging and age-related disease. The interplay between splicing and aging has major implications for aging biology, though differentiating correlation and causation remains challenging. Declaring a splicing factor or event as a driver requires comprehensive evaluation of the associated molecular and physiological changes. A greater understanding of how RNA splicing machinery and downstream targets are impacted by aging is essential to conclusively establish the role of splicing in driving aging, representing a promising area with key implications for understanding aging, developing novel therapeutical options, and ultimately leading to an increase in the healthy human lifespan.
    Keywords:  age-associated splicing events; age-related diseases; aging; alternative splicing; molecular aging; senescence; splice variants; splicing factors; splicing regulation; transcriptome changes
    DOI:  https://doi.org/10.3390/cells12242819
  6. Curr Opin Hematol. 2023 Dec 18.
    Age-related micro-environmental changes as drivers of clonal hematopoiesis.
    Tal Bacharach, Nathali Kaushansky, Liran I Shlush.
       PURPOSE OF REVIEW: Both aging and reduced diversity at the hematopoietic stem cells (HSCs) level are ubiquitous. What remains unclear is why some individuals develop clonal hematopoiesis (CH), and why does CH due to specific mutations occur in specific individuals. Much like aging, reduced diversity of HSCs is a complex phenotype shaped by numerous factors (germline & environment). The purpose of the current review is to discuss the role of two other age-related ubiquitous processes that might contribute to the dynamics and characteristics of losing HSC diversity and the evolution of CH. These processes have not been reviewed in depth so far and include the accumulation of fatty bone marrow (FBM), and the decline in sex hormones.
    RECENT FINDINGS: Interestingly, sex hormone decline can directly shape HSC function, but also reshape the delicate balance of BM supporting cells, with a shift towards FBM. FBM accumulation can shape the clonal expansion of preleukemic mutations, particularly DNMT3A mutations, through IL-6 mediation. DNMT3A mutations are one of the only preleukemic mutations which is more prevalent in women, and especially in women with early menopause, demonstrating an association between age-related hormone decline and CH evolution, the mechanisms of which are yet to be discovered.
    SUMMARY: Aging is a multifactorial phenotype and the same is true for the aging of the blood system. While many factors which can shape CH have been discussed, we shed more light on FBM and sex hormone decline. Much more is missing: how and should we even try to prevent these phenomena? Why do they occur? and how they are connected to other age-related blood factors?
    DOI:  https://doi.org/10.1097/MOH.0000000000000798
  7. Acta Dermatovenerol Alp Pannonica Adriat. 2023 12;32(4): 159-164
    New anti-aging strategies: a narrative review.
    Vana Stojić, Tea Štrbac, Andrija Stanimirović.
      The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and cardiovascular and neurodegenerative diseases. This review provides an overview of the latest advancements in this field, considering both pharmaceutical and non-pharmaceutical approaches. Electronic literature search involved three databases: MEDLINE, Cochrane, and Google Scholar, supplemented by other available literature. Strategies for delaying aging and related diseases comprise pharmaceutical interventions and lifestyle choices. It is crucial for these strategies to be substantiated by research-based evidence. Lifestyle options include fasting, fasting-mimicking, and ketogenic diets. Anti-aging drugs and supplements operate through diverse mechanisms. Calorie restriction mimetics include the activator of AMP-activated protein kinase (metformin) and inhibitor of mTOR (rapamycin), alongside rilmenidine, exhibiting both effects. Rosmarinic acid, a natural product, functions through its anti-glycation properties. Age-related protein crosslinks are acknowledged as a causative factor in age-related diseases. Anti-aging medicine is an evolving field with a multitude of drugs and strategies, necessitating further clinical studies and long-term follow-up based on clinical experience and insights gained from delayed adverse events.
  8. Front Med (Lausanne). 2023 ;10 1335119
    Editorial: The role of nutrition in healthy aging.
    Roberta Zupo, Fabio Castellana, Hélio José Coelho Júnior, Giovanni De Pergola, Maria Lisa Clodoveo, Rodolfo Sardone.
      
    Keywords:  aging; diet; epidemiology; nutrition; public health
    DOI:  https://doi.org/10.3389/fmed.2023.1335119
  9. Epigenomics. 2023 Dec 19.
    The epigenetics of frailty.
    Madia Lozupone, Vincenzo Solfrizzi, Rodolfo Sardone, Vittorio Dibello, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Antonio Daniele, Francesco Panza.
      The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.
    Keywords:  DNA methylation; diet; epigenetics; frailty; multimorbidity; psychosocial
    DOI:  https://doi.org/10.2217/epi-2023-0279
  10. Clin Sci (Lond). 2023 Dec 22. 137(24): 1805-1821
    Cellular senescence and kidney aging.
    Nikolai Rex, Anette Melk, Roland Schmitt.
      Life expectancy is increasing worldwide, and by 2050 the proportion of the world's population over 65 years of age is estimated to surpass 1.5 billion. Kidney aging is associated with molecular and physiological changes that cause a loss of renal function and of regenerative potential. As the aging population grows, it is crucial to understand the mechanisms underlying these changes, as they increase the susceptibility to developing acute kidney injury (AKI) and chronic kidney disease (CKD). Various cellular processes and molecular pathways take part in the complex process of kidney aging. In this review, we will focus on the phenomenon of cellular senescence as one of the involved mechanisms at the crossroad of kidney aging, age-related disease, and CKD. We will highlight experimental and clinical findings about the role of cellular senescence in kidney aging and CKD. In addition, we will review challenges in senescence research and emerging therapeutic aspects. We will highlight the great potential of senolytic strategies for the elimination of harmful senescent cells to promote healthy kidney aging and to avoid age-related disease and CKD. This review aims to give insight into recent discoveries and future developments, providing a comprehensive overview of current knowledge on cellular senescence and anti-senescent therapies in the kidney field.
    Keywords:  Aging kidney; Cellular Senescence; chronic kidney disease; senolysis; senolytic therapy
    DOI:  https://doi.org/10.1042/CS20230140
  11. Nature. 2024 Jan;625(7993): 35-36
    Muscle immune cells protect mitochondrial organelles during exercise.
    Gerald Coulis, S Armando Villalta.
      
    Keywords:  Cell biology; Immunology; Physiology
    DOI:  https://doi.org/10.1038/d41586-023-03972-w
  12. Cells. 2023 Dec 07. pii: 2785. [Epub ahead of print]12(24):
    Aging and Metabolic Reprogramming of Adipose-Derived Stem Cells Affect Molecular Mechanisms Related to Cardiovascular Diseases.
    Paul Holvoet.
      We performed a systematic search of the PubMed database for English-language articles related to the function of adipose-derived stem cells in the pathogenesis of cardiovascular diseases. In preclinical models, adipose-derived stem cells protected arteries and the heart from oxidative stress and inflammation and preserved angiogenesis. However, clinical trials did not reiterate successful treatments with these cells in preclinical models. The low success in patients may be due to aging and metabolic reprogramming associated with the loss of proliferation capacity and increased senescence of stem cells, loss of mitochondrial function, increased oxidative stress and inflammation, and adipogenesis with increased lipid deposition associated with the low potential to induce endothelial cell function and angiogenesis, cardiomyocyte survival, and restore heart function. Then, we identify noncoding RNAs that may be mechanistically related to these dysfunctions of human adipose-derived stem cells. In particular, a decrease in let-7, miR-17-92, miR-21, miR-145, and miR-221 led to the loss of their function with obesity, type 2 diabetes, oxidative stress, and inflammation. An increase in miR-34a, miR-486-5p, and mir-24-3p contributed to the loss of function, with a noteworthy increase in miR-34a with age. In contrast, miR-146a and miR-210 may protect stem cells. However, a systematic analysis of other noncoding RNAs in human adipose-derived stem cells is warranted. Overall, this review gives insight into modes to improve the functionality of human adipose-derived stem cells.
    Keywords:  adipose; atherosclerosis; heart disease; inflammation; oxidative stress; stem cells
    DOI:  https://doi.org/10.3390/cells12242785
  13. Biochemistry (Mosc). 2023 Nov;88(11): 1763-1777
    Microgravity Effects and Aging Physiology: Similar Changes or Common Mechanisms?
    Andrey Yu Ratushnyy, Ludmila B Buravkova.
      Despite the use of countermeasures (including intense physical activity), cosmonauts and astronauts develop muscle atony and atrophy, cardiovascular system failure, osteopenia, etc. All these changes, reminiscent of age-related physiological changes, occur in a healthy person in microgravity quite quickly - within a few months. Adaptation to the lost of gravity leads to the symptoms of aging, which are compensated after returning to Earth. The prospect of interplanetary flights raises the question of gravity thresholds, below which the main physiological systems will decrease their functional potential, similar to aging, and affect life expectancy. An important role in the aging process belongs to the body's cellular reserve - progenitor cells, which are involved in physiological remodeling and regenerative/reparative processes of all physiological systems. With age, progenitor cell count and their regenerative potential decreases. Moreover, their paracrine profile becomes pro-inflammatory during replicative senescence, disrupting tissue homeostasis. Mesenchymal stem/stromal cells (MSCs) are mechanosensitive, and therefore deprivation of gravitational stimulus causes serious changes in their functional status. The review compares the cellular effects of microgravity and changes developing in senescent cells, including stromal precursors.
    Keywords:  aging; cell senescence; mesenchymal stem/stromal cells (MSCs); microgravity
    DOI:  https://doi.org/10.1134/S0006297923110081
  14. Cell Metab. 2023 Dec 14. pii: S1550-4131(23)00449-7. [Epub ahead of print]
    Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.
    Riley J Wedan, Jacob Z Longenecker, Sara M Nowinski.
      Contrary to their well-known functions in nutrient breakdown, mitochondria are also important biosynthetic hubs and express an evolutionarily conserved mitochondrial fatty acid synthesis (mtFAS) pathway. mtFAS builds lipoic acid and longer saturated fatty acids, but its exact products, their ultimate destination in cells, and the cellular significance of the pathway are all active research questions. Moreover, why mitochondria need mtFAS despite their well-defined ability to import fatty acids is still unclear. The identification of patients with inborn errors of metabolism in mtFAS genes has sparked fresh research interest in the pathway. New mammalian models have provided insights into how mtFAS coordinates many aspects of oxidative mitochondrial metabolism and raise questions about its role in diseases such as obesity, diabetes, and heart failure. In this review, we discuss the products of mtFAS, their function, and the consequences of mtFAS impairment across models and in metabolic disease.
    Keywords:  fatty acids; inborn errors of metabolism; lipid metabolism; lipids; mitochondria; mitochondrial fatty acid synthesis; mouse models; mtFAS
    DOI:  https://doi.org/10.1016/j.cmet.2023.11.017
  15. J Clin Med. 2023 Dec 17. pii: 7738. [Epub ahead of print]12(24):
    Inflammation in Heart Failure-Future Perspectives.
    Alexandru Mircea Arvunescu, Ruxandra Florentina Ionescu, Sanda Maria Cretoiu, Silviu Ionel Dumitrescu, Ondin Zaharia, Ioan Tiberiu Nanea.
      Chronic heart failure is a terminal point of a vast majority of cardiac or extracardiac causes affecting around 1-2% of the global population and more than 10% of the people above the age of 65. Inflammation is persistently associated with chronic diseases, contributing in many cases to the progression of disease. Even in a low inflammatory state, past studies raised the question of whether inflammation is a constant condition, or if it is, rather, triggered in different amounts, according to the phenotype of heart failure. By evaluating the results of clinical studies which focused on proinflammatory cytokines, this review aims to identify the ones that are independent risk factors for heart failure decompensation or cardiovascular death. This review assessed the current evidence concerning the inflammatory activation cascade, but also future possible targets for inflammatory response modulation, which can further impact the course of heart failure.
    Keywords:  CRP; IL-1; IL-6; TNF-α; fibrinogen; heart failure; iNOS; inflammation; myeloperoxidase; proinflammatory cytokines
    DOI:  https://doi.org/10.3390/jcm12247738
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