bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–02–26
sixteen papers selected by
Ayesh Seneviratne, Western University
  1. Clonal Hematopoiesis: Connecting Aging and Inflammation in Atherosclerosis.
  2. Increased alcohol dehydrogenase 1 activity promotes longevity.
  3. Clonal hematopoiesis: the nonhereditary genetics of age-associated cardiovascular disease.
  4. [Clonal Hematopoiesis and Solid Cancer].
  5. A Wrong Fate Decision in Adipose Stem Cells upon Obesity.
  6. The effects of macronutrients metabolism on cellular and organismal aging.
  7. Stochastic fate decisions of HSCs after transplantation: early contribution, symmetric expansion, and pool formation.
  8. The Role of CD38 in the Pathogenesis of Cardiorenal Metabolic Disease and Aging, an Approach from Basic Research.
  9. Clonal hematopoiesis onset in chronic myeloid leukemia patients developing an adverse cardiovascular event.
  10. Editorial: Phospholipids and sphingolipids in nutrition, metabolism, and health.
  11. Successful aging and its subtypes in centenarians: The Chinese experience.
  12. Unsaturated Fatty Acids and Their Immunomodulatory Properties.
  13. Extracellular Vesicles in Aging: An Emerging Hallmark?
  14. CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.
  15. Cellular senescence: when growth stimulation meets cell cycle arrest.
  16. How Nature readers are using ChatGPT.
  1. Curr Atheroscler Rep. 2023 Mar;25(3): 105-111
    Clonal Hematopoiesis: Connecting Aging and Inflammation in Atherosclerosis.
    Ariel H Polizio, Eunbee Park, Kenneth Walsh.
       PURPOSE OF REVIEW: Clonal hematopoiesis (CH) is a prevalent condition that results from the acquisition of somatic mutations in hematopoietic stem cells. When these mutations occur in "driver" genes, they can potentially confer fitness advantages to the cell, leading to a clonal expansion. While most clonal expansions of mutant cells are generally considered to be asymptomatic since they do not impact overall blood cell numbers, CH carriers display long-term risks of all-cause mortality and age-associated diseases including cardiovascular disease (CVD). This review summarizes recent findings in CH related to aging, atherosclerotic CVD, and inflammation, emphasizing epidemiological and mechanistic studies, and potential therapeutic options to treat CVDs that are promoted by CH.
    RECENT FINDINGS: Epidemiological studies have revealed associations between CH and CVDs. Experimental studies with CH models employing the Tet2- and Jak2-mutant mouse lines display inflammasome activation and a chronic inflammatory state that leads to accelerated atherosclerotic lesion growth. A body of evidence suggests that CH represents a new causal risk factor for CVD. Studies also indicate that understanding an individual's CH status could provide guidance for personalized approaches to treat atherosclerosis and other CVDs with anti-inflammatory drugs.
    Keywords:  Age-related clonal hematopoiesis; CANTOS; Clonal hematopoiesis of indeterminate potential; Inflammasome
    DOI:  https://doi.org/10.1007/s11883-023-01083-5
  2. Curr Biol. 2023 Feb 16. pii: S0960-9822(23)00128-8. [Epub ahead of print]
    Increased alcohol dehydrogenase 1 activity promotes longevity.
    Abbas Ghaddar, Vinod K Mony, Swarup Mishra, Samuel Berhanu, James C Johnson, Elisa Enriquez-Hesles, Emma Harrison, Aaroh Patel, Mary Kate Horak, Jeffrey S Smith, Eyleen J O'Rourke.
      Several molecules can extend healthspan and lifespan across organisms. However, most are upstream signaling hubs or transcription factors orchestrating complex anti-aging programs. Therefore, these molecules point to but do not reveal the fundamental mechanisms driving longevity. Instead, downstream effectors that are necessary and sufficient to promote longevity across conditions or organisms may reveal the fundamental anti-aging drivers. Toward this goal, we searched for effectors acting downstream of the transcription factor EB (TFEB), known as HLH-30 in C. elegans, because TFEB/HLH-30 is necessary across anti-aging interventions and its overexpression is sufficient to extend C. elegans lifespan and reduce biomarkers of aging in mammals including humans. As a result, we present an alcohol-dehydrogenase-mediated anti-aging response (AMAR) that is essential for C. elegans longevity driven by HLH-30 overexpression, caloric restriction, mTOR inhibition, and insulin-signaling deficiency. The sole overexpression of ADH-1 is sufficient to activate AMAR, which extends healthspan and lifespan by reducing the levels of glycerol-an age-associated and aging-promoting alcohol. Adh1 overexpression is also sufficient to promote longevity in yeast, and adh-1 orthologs are induced in calorically restricted mice and humans, hinting at ADH-1 acting as an anti-aging effector across phyla.
    Keywords:  aging, healthspan; alcohol; aldehyde; caloric restriction; glycerol; hlh-30/TFEB; lifespan; longevity; mTOR/insulin signaling
    DOI:  https://doi.org/10.1016/j.cub.2023.01.059
  3. Curr Opin Cardiol. 2023 Feb 22.
    Clonal hematopoiesis: the nonhereditary genetics of age-associated cardiovascular disease.
    Soichi Sano, Mark C Thel, Kenneth Walsh.
       PURPOSE OF REVIEW: Somatic mutations, described as noninherited changes in DNA that arise and are passed on to descendant cells, are well known to cause cancers; however, it is increasingly appreciated that the propagation of somatic mutations within a tissue may have a role in causing nonneoplastic disorders and abnormalities in elderly individuals. The nonmalignant clonal expansion of somatic mutations in the hematopoietic system is termed clonal hematopoiesis. This review will briefly discuss how this condition has been linked to various age-related diseases outside the hematopoietic system.
    RECENT FINDINGS: Clonal hematopoiesis, resulting from leukemic driver gene mutations or mosaic loss of the Y chromosome in leukocytes, is associated with the development of various forms of cardiovascular disease, including atherosclerosis and heart failure, in a mutation-dependent manner.
    SUMMARY: Accumulating evidence shows that clonal hematopoiesis represents a new mechanism for cardiovascular disease and a new risk factor that is as prevalent and consequential as the traditional risk factors that have been studied for decades.
    DOI:  https://doi.org/10.1097/HCO.0000000000001032
  4. Gan To Kagaku Ryoho. 2023 Feb;50(2): 129-133
    [Clonal Hematopoiesis and Solid Cancer].
    Mamiko Sakata-Yanagimoto, Kenichi Makishima, Yasuhito Suehara.
      In the hematopoietic system of healthy individuals, a phenomenon called clonal hematopoiesis, in which cells acquired somatic mutations are replaced with aging, has been discovered. The frequency of clonal hematopoiesis is higher in patients with solid tumors, than normal individuals. In addition, it is thought that infiltration of inflammatory cells with somatic mutations into cancer tissues may change the tumor microenvironment. Since clonal hematopoiesis is often found incidentally in gene panel testing of solid cancer tissues, it is of great significance to have an insight into clonal hematopoiesis in the medical care of solid cancer patients. In this paper, we describe the general concept of clonal hematopoiesis, the frequency of clonal hematopoiesis in patients with solid tumors, the characteristics of the clinical course in patients with clonal hematopoiesis, and microscopic observations of solid tumors in mouse models of clonal hematopoiesis.
  5. Cells. 2023 Feb 19. pii: 662. [Epub ahead of print]12(4):
    A Wrong Fate Decision in Adipose Stem Cells upon Obesity.
    Yiu-Ming Cheung, Chui-Yiu-Bamboo Chook, Hoi-Wa Yeung, Fung-Ping Leung, Wing-Tak Wong.
      Progress has been made in identifying stem cell aging as a pathological manifestation of a variety of diseases, including obesity. Adipose stem cells (ASCs) play a core role in adipocyte turnover, which maintains tissue homeostasis. Given aberrant lineage determination as a feature of stem cell aging, failure in adipogenesis is a culprit of adipose hypertrophy, resulting in adiposopathy and related complications. In this review, we elucidate how ASC fails in entering adipogenic lineage, with a specific focus on extracellular signaling pathways, epigenetic drift, metabolic reprogramming, and mechanical stretch. Nonetheless, such detrimental alternations can be reversed by guiding ASCs towards adipogenesis. Considering the pathological role of ASC aging in obesity, targeting adipogenesis as an anti-obesity treatment will be a key area of future research, and a strategy to rejuvenate tissue stem cell will be capable of alleviating metabolic syndrome.
    Keywords:  adipogenesis; fate determination; hypertrophic obesity; inflammation; stem cell aging
    DOI:  https://doi.org/10.3390/cells12040662
  6. Biomed J. 2023 Feb 15. pii: S2319-4170(23)00009-4. [Epub ahead of print]
    The effects of macronutrients metabolism on cellular and organismal aging.
    Jamil Nehme, Abdullah Altulea, Teodora Gheorghe, Marco Demaria.
      Evidence supports the notion that metabolic pathways are major regulators of organismal aging, and that metabolic perturbations can extend health- and lifespan. For this reason, dietary interventions and compounds perturbing metabolism are currently explored as anti-aging strategies. A common target for metabolic interventions delaying aging is cellular senescence, a state of stable growth arrest that is accompanied by various structural and functional changes including the activation of a pro-inflammatory secretome. Here, we summarize the current knowledge on the molecular and cellular events associated with carbohydrate, lipid and protein metabolism, and define how macronutrients can regulate induction or prevention of cellular senescence. We discuss how various dietary interventions can achieve prevention of disease and extension of healthy longevity by partially modulating senescence-associated phenotypes. We also emphasize the importance of developing personalized nutritional interventions that take into account the current health and age status of the individual.
    Keywords:  aging; macronutrients; metabolism; senescence
    DOI:  https://doi.org/10.1016/j.bj.2023.02.005
  7. Blood. 2023 Feb 23. pii: blood.2022018564. [Epub ahead of print]
    Stochastic fate decisions of HSCs after transplantation: early contribution, symmetric expansion, and pool formation.
    Stefan Radtke, Mark R Enstrom, Dnyanada Pande, Elizabeth R Duke, Erwing Fabian Cardozo Ojeda, Ravishankar Madhu, Staci Owen, Greta Kanestrom, Margaret Lee Cui, Anai M Perez, Joshua T Schiffer, Hans-Peter Kiem.
      Hematopoietic stem cells (HSCs) are assumed to be rare, infrequently dividing, long-lived, and not involved in immediate recovery after transplantation. Here we performed unprecedented high-density clonal tracking in nonhuman primates and found long-term persisting HSC clones to actively contribute during early neutrophil recovery and be the main source of blood production as early as 50 days post-transplant. Most surprisingly, we observed a rapid decline in the number of unique HSC clones, while persisting HSCs expanded undergoing symmetric divisions to create identical siblings and formed clonal pools ex vivo as well as in vivo. In contrast to the currently assumed model of hematopoietic reconstitution, we provide evidence for contribution of HSCs in short-term recovery as well as symmetric expansion of individual clones into pools. These findings provide novel insights into HSC biology informing the design of HSC transplantation and gene therapy studies.
    DOI:  https://doi.org/10.1182/blood.2022018564
  8. Cells. 2023 Feb 12. pii: 595. [Epub ahead of print]12(4):
    The Role of CD38 in the Pathogenesis of Cardiorenal Metabolic Disease and Aging, an Approach from Basic Research.
    Munehiro Kitada, Shin-Ichi Araki, Daisuke Koya.
      Aging is a major risk factor for the leading causes of mortality, and the incidence of age-related diseases including cardiovascular disease, kidney disease and metabolic disease increases with age. NAD+ is a classic coenzyme that exists in all species, and that plays a crucial role in oxidation-reduction reactions. It is also involved in the regulation of many cellular functions including inflammation, oxidative stress and differentiation. NAD+ declines with aging in various organs, and the reduction in NAD+ is possibly involved in the development of age-related cellular dysfunction in cardiorenal metabolic organs through the accumulation of inflammation and oxidative stress. Levels of NAD+ are regulated by the balance between its synthesis and degradation. CD38 is the main NAD+-degrading enzyme, and CD38 is activated in response to inflammation with aging, which is associated with the reduction in NAD+ levels. In this review, focusing on CD38, we discuss the role of CD38 in aging and the pathogenesis of age-related diseases, including cardiorenal metabolic disease.
    Keywords:  CD38; NAD+; aging; cardiovascular disease; kidney disease; metabolic disease
    DOI:  https://doi.org/10.3390/cells12040595
  9. Leuk Res. 2023 Jan 24. pii: S0145-2126(23)00008-5. [Epub ahead of print]127 107023
    Clonal hematopoiesis onset in chronic myeloid leukemia patients developing an adverse cardiovascular event.
    Francesco Tarantini, Cosimo Cumbo, Antonella Zagaria, Luisa Anelli, Elisa Parciante, Immacolata Redavid, Nicoletta Coccaro, Giuseppina Tota, Maria Rosa Conserva, Crescenzio Francesco Minervini, Angela Minervini, Immacolata Attolico, Antonella Russo Rossi, Giorgina Specchia, Pellegrino Musto, Francesco Albano.
      Life expectation of chronic myeloid leukemia patients in the tyrosine kinase inhibitors era is almost equal to that of healthy subjects. On the other hand, their long-term management must take into account a higher risk of adverse events, at least partly related to the treatment. Various studies reported a higher incidence of cardiovascular events in these patients. Clonal hematopoiesis is broadly considered a major independent risk factor for cardiovascular events. Of note, the underlying physiopathological mechanisms connect clonal hematopoiesis with a global proinflammatory status, triggering a vicious circle in which the somatic mutations and inflammation feed each other. All this considered, we investigated the occurrence of clonal hematopoiesis in chronic myeloid leukemia patients developing a cardiovascular event under tyrosine kinase inhibitor therapy.
    Keywords:  Cardiovascular events; Chronic myeloid leukemia; Clonal hematopoiesis; Tyrosine kinase inhibitors
    DOI:  https://doi.org/10.1016/j.leukres.2023.107023
  10. Front Nutr. 2023 ;10 1153138
    Editorial: Phospholipids and sphingolipids in nutrition, metabolism, and health.
    Ronan Lordan, Christopher N Blesso.
      
    Keywords:  gangliosides; glycolipids; inflammation; lipid metabolism; phospholipids; sphingolipids
    DOI:  https://doi.org/10.3389/fnut.2023.1153138
  11. J Am Geriatr Soc. 2023 Feb 21.
    Successful aging and its subtypes in centenarians: The Chinese experience.
    Thomas Perls.
      
    DOI:  https://doi.org/10.1111/jgs.18282
  12. Biology (Basel). 2023 Feb 09. pii: 279. [Epub ahead of print]12(2):
    Unsaturated Fatty Acids and Their Immunomodulatory Properties.
    Salvatore Coniglio, Maria Shumskaya, Evros Vassiliou.
      Oils are an essential part of the human diet and are primarily derived from plant (or sometimes fish) sources. Several of them exhibit anti-inflammatory properties. Specific diets, such as Mediterranean diet, that are high in ω-3 polyunsaturated fatty acids (PUFAs) and ω-9 monounsaturated fatty acids (MUFAs) have even been shown to exert an overall positive impact on human health. One of the most widely used supplements in the developed world is fish oil, which contains high amounts of PUFAs docosahexaenoic and eicosapentaenoic acid. This review is focused on the natural sources of various polyunsaturated and monounsaturated fatty acids in the human diet, and their role as precursor molecules in immune signaling pathways. Consideration is also given to their role in CNS immunity. Recent findings from clinical trials utilizing various fatty acids or diets high in specific fatty acids are reviewed, along with the mechanisms through which fatty acids exert their anti-inflammatory properties. An overall understanding of diversity of polyunsaturated fatty acids and their role in several molecular signaling pathways is useful in formulating diets that reduce inflammation and increase longevity.
    Keywords:  immunity; inflammation; microglia; omega-3; omega-6; polyunsaturated fatty acids
    DOI:  https://doi.org/10.3390/biology12020279
  13. Cells. 2023 Feb 06. pii: 527. [Epub ahead of print]12(4):
    Extracellular Vesicles in Aging: An Emerging Hallmark?
    Giorgia Manni, Sandra Buratta, Maria Teresa Pallotta, Davide Chiasserini, Alessandro Di Michele, Carla Emiliani, Stefano Giovagnoli, Luisa Pascucci, Rita Romani, Ilaria Bellezza, Lorena Urbanelli, Francesca Fallarino.
      Extracellular vesicles (EVs) are membrane-enclosed particles secreted by cells and circulating in body fluids. Initially considered as a tool to dispose of unnecessary material, they are now considered an additional method to transmit cell signals. Aging is characterized by a progressive impairment of the physiological functions of tissues and organs. The causes of aging are complex and interconnected, but there is consensus that genomic instability, telomere erosion, epigenetic alteration, and defective proteostasis are primary hallmarks of the aging process. Recent studies have provided evidence that many of these primary stresses are associated with an increased release of EVs in cell models, able to spread senescence signals in the recipient cell. Additional investigations on the role of EVs during aging also demonstrated the great potential of EVs for the modulation of age-related phenotypes and for pro-rejuvenation therapies, potentially beneficial for many diseases associated with aging. Here we reviewed the current literature on EV secretion in senescent cell models and in old vs. young individual body fluids, as well as recent studies addressing the potential of EVs from different sources as an anti-aging tool. Although this is a recent field, the robust consensus on the altered EV release in aging suggests that altered EV secretion could be considered an emerging hallmark of aging.
    Keywords:  aging; extracellular vesicles (EVs); senescence; senescence-associated secretory phenotype (SASP)
    DOI:  https://doi.org/10.3390/cells12040527
  14. Nat Immunol. 2023 Feb 23.
    CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions.
    Pu-Ste Liu, Yi-Ting Chen, Xiaoyun Li, Pei-Chun Hsueh, Sheue-Fen Tzeng, Hsi Chen, Pei-Zhu Shi, Xin Xie, Sweta Parik, Mélanie Planque, Sarah-Maria Fendt, Ping-Chih Ho.
      Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD+/NADH ratio via glutamine-to-lactate conversion. Genetic ablation of important metabolic enzymes involved in CD40-mediated metabolic reprogramming abolishes agonistic anti-CD40-induced antitumor responses and reeducation of tumor-associated macrophages. Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments.
    DOI:  https://doi.org/10.1038/s41590-023-01430-3
  15. Aging (Albany NY). 2023 Feb 19. 15
    Cellular senescence: when growth stimulation meets cell cycle arrest.
    Mikhail V Blagosklonny.
      At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.
    Keywords:  cell volume and enlargement; gerogenic conversion; hyperfunction theory of aging; mTOR; rapamycin
    DOI:  https://doi.org/10.18632/aging.204543
  16. Nature. 2023 Feb 20.
    How Nature readers are using ChatGPT.
    Brian Owens.
      
    Keywords:  Computer science; Machine learning; Scientific community
    DOI:  https://doi.org/10.1038/d41586-023-00500-8
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