bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022–09–25
fourteen papers selected by
Ayesh Seneviratne, Western University
  1. Experimental ASXL1-Mediated Clonal Hematopoiesis Promotes Inflammation and Accelerates Heart Failure.
  2. Clonal Hematopoiesis: Role in Hematologic and Non-Hematologic Malignancies.
  3. Weight strategy in older adults with obesity: calorie restriction or not?
  4. Clinical manifestations of clonal hematopoiesis: What has SF3B1-mutant MDS taught us?
  5. The Combined Effects of Dietary Diversity and Frailty on Mortality in Older Taiwanese People.
  6. A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome.
  7. Biological Restraints on Indefinite Survival.
  8. Methods for Successful Aging: An Aesthetics-Oriented Perspective Derived from Richard Shusterman's Somaesthetics.
  9. Biologia Futura: four questions about ageing and the future of relevant animal models.
  10. The Benefits of a Sense of Purpose in Life for Healthier Cognitive Aging.
  11. Targeting cellular senescence in metabolic disease.
  12. Circular RNAs Involved in the Regulation of the Age-Related Pathways.
  13. The role of aging in cancer.
  14. Tafazzin deficiency attenuates anti-cluster of differentiation 40 and interleukin-4 activation of mouse B lymphocytes.
  1. J Am Heart Assoc. 2022 Sep 21. e026154
    Experimental ASXL1-Mediated Clonal Hematopoiesis Promotes Inflammation and Accelerates Heart Failure.
    Kyung-Duk Min, Ariel H Polizio, Anupreet Kour, Mark C Thel, Kenneth Walsh.
      
    Keywords:  aged; aging; cardiovascular diseases; cause of death; clonal hematopoiesis; stroke volume; ventricular function, left
    DOI:  https://doi.org/10.1161/JAHA.122.026154
  2. Mediterr J Hematol Infect Dis. 2022 ;14(1): e2022069
    Clonal Hematopoiesis: Role in Hematologic and Non-Hematologic Malignancies.
    Ugo Testa, Germana Castelli, Elvira Pelosi.
      Hematopoietic stem cells (HSCs) ensure the coordinated and balanced production of all hematopoietic cell types throughout life. Aging is associated with a gradual decline of the self-renewal and regenerative potential of HSCs and with the development of clonal hematopoiesis. Clonal hematopoiesis of indeterminate potential (CHIP) defines the clonal expansion of genetically variant hematopoietic cells bearing one or more gene mutations and/or structural variants (such as copy number alterations). CHIP increases exponentially with age and is associated with cancers, including hematologic neoplasia, cardiovascular and other diseases. The presence of CHIP consistently increases the risk of hematologic malignancy, particularly in individuals who have CHIP in association with peripheral blood cytopenia.
    Keywords:  Clonal hematopoiesis; Gene mutations; Hematopoiesis; Hematopoietic stem cells; Next generation sequencing
    DOI:  https://doi.org/10.4084/MJHID.2022.069
  3. Curr Opin Clin Nutr Metab Care. 2022 Sep 20.
    Weight strategy in older adults with obesity: calorie restriction or not?
    Georgia Colleluori, Dennis T Villareal.
       PURPOSE OF REVIEW: Along with the marked increase in the population of older adults with obesity is the need for effective strategies to treat aging- and obesity-related complications. This review highlights recent progress in obesity management in older adults.
    RECENT FINDINGS: Although calorie restriction is needed to significantly reduce fat mass, an exercise protocol is crucial to ameliorate functional outcomes. The addition of a resistance exercise protocol improves the response of muscle protein synthesis to anabolic stimuli, preventing the calorie restriction-induced reduction in muscle and bone mass. The addition of an aerobic exercise protocol improves cardiorespiratory fitness and cognitive function. However, the addition of both aerobic and resistance exercise protocols to calorie restriction provides the greatest improvements in myocellular quality, frailty, and cardiometabolic and cognitive outcomes, translating into the greatest improvement in quality of life. Such comprehensive lifestyle intervention effectively improves glucometabolic control and age-relevant outcomes in older adults with diabetes. When combined with testosterone therapy, such lifestyle intervention also preserves muscle and bone mass in older, men with obesity and hypogonadism.
    SUMMARY: We conclude that calorie restriction among older adults with obesity should be prescribed in combination with both aerobic and resistance exercise to maximize benefits on overall health.
    DOI:  https://doi.org/10.1097/MCO.0000000000000879
  4. Semin Hematol. 2022 Jul;pii: S0037-1963(22)00042-7. [Epub ahead of print]59(3): 150-155
    Clinical manifestations of clonal hematopoiesis: What has SF3B1-mutant MDS taught us?
    Gabriele Todisco, Pedro L Moura, Eva Hellström-Lindberg.
      Large scale high-throughput DNA sequencing studies have identified clonal hematopoiesis (CH) as a clinical phenomenon characterized by a disproportionately large clonal population in the hematopoietic system with a shared mutational background. CH originates through mutations in hematopoietic stem and progenitor cells (HSPCs) which provide a proliferative advantage over unmutated HSPCs and has been characterized as a risk factor for myeloid neoplasm (MN) development. Large population studies found that CH is an age-related event which is commonly found in association with milder phenotypes such as cytopenia, mild monocytosis, intravascular hemolysis, or chronic inflammation. More importantly, the vast majority of individuals with CH are asymptomatic and healthy people of advanced age, where the impact of CH is thus considered to be of indeterminate potential (CHIP). These conditions are sometimes referred to as benign to facilitate distinction from overt MN but, despite this definition, may still result in severe illness, reduced overall survival, and increased risk of hematologic neoplasms development and all-cause mortality. The purpose of this review is to describe clinical conditions associated with CH, the clinical significance of CH-related clinical phenotypes, and the determinants of progression from CH to overt MN following the paradigmatic example of SF3B1-driven CH.
    Keywords:  CCUS; CHIP; MDS; SF3B1; clonal hematopoiesis
    DOI:  https://doi.org/10.1053/j.seminhematol.2022.08.002
  5. Nutrients. 2022 Sep 16. pii: 3825. [Epub ahead of print]14(18):
    The Combined Effects of Dietary Diversity and Frailty on Mortality in Older Taiwanese People.
    Wei-Ching Huang, Yi-Chen Huang, Meei-Shyuan Lee, Jia-Yau Doong, Wen-Harn Pan, Hsing-Yi Chang.
       OBJECTIVE: To assess the prospective association between frailty and dietary diversity on mortality.
    METHOD: This prospective cohort study used the 2005-2008 Nutrition and Health Survey in Taiwan (N = 330; age ≥ 65 years) and this was linked to the Death Registry where we used the data that was recorded up to 31 January 2020. Dietary intake information was assessed using a 24-h dietary recall and food-frequency questionnaire, which were calculated a dietary diversity score (DDS; range, 0-6) and food consumption frequency. Assessment of frailty phenotypes was based on FRAIL scale which was proposed by the International Academy on Nutrition and Aging.
    RESULTS: Frail older adults had a higher risk of all-cause mortality when they were compared to those with robust physiologies (hazard ratio [HR]: 3.73, 95% confidence interval [CI]: 2.13-6.52). Frailty and a lower DDS were associated with a higher risk of mortality (joint adjusted HR: 2.30, 95% CI: 1.11-4.75) which, compared with a robust physiology and higher DDS, were associated with a lower risk of mortality.
    CONCLUSIONS: Frailty and a lower DDS were associated with a higher mortality. Prefrailty and frailty with a higher DDS were associated with a lower risk of mortality when compared with those with prefrailty and frailty and a lower DDS. These results suggest that eating a wide variety of foods might reduce the risk of mortality in older adults with prefrailty and frailty.
    Keywords:  Nutrition and Health Survey in Taiwan (NAHSIT); dietary diversity; frailty; mortality; older adults
    DOI:  https://doi.org/10.3390/nu14183825
  6. Leukemia. 2022 Sep 21.
    A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome.
    Héléna Boutzen, Seyed Ali Madani Tonekaboni, Michelle Chan-Seng-Yue, Alex Murison, Naoya Takayama, Nathan Mbong, Elvin Wagenblast, Elias Orouji, Andrea Arruda, Amanda Mitchell, Faiyaz Notta, Mark D Minden, Mathieu Lupien, Kerstin B Kaufmann, John E Dick.
      Many cancers are organized as cellular hierarchies sustained by cancer stem cells (CSC), whose eradication is crucial for achieving long-term remission. Difficulties to isolate and undertake in vitro and in vivo experimental studies of rare CSC under conditions that preserve their original properties currently constitute a bottleneck for identifying molecular mechanisms involving coding and non-coding genomic regions that govern stemness. We focussed on acute myeloid leukemia (AML) as a paradigm of the CSC model and developed a patient-derived system termed OCI-AML22 that recapitulates the cellular hierarchy driven by leukemia stem cells (LSC). Through classical flow sorting and functional analyses, we established that a single phenotypic population is highly enriched for LSC. The LSC fraction can be easily isolated and serially expanded in culture or in xenografts while faithfully recapitulating functional, transcriptional and epigenetic features of primary LSCs. A novel non-coding regulatory element was identified with a new computational approach using functionally validated primary AML LSC fractions and its role in LSC stemness validated through efficient CRISPR editing using methods optimized for OCI-AML22 LSC. Collectively, OCI-AML22 constitutes a valuable resource to uncover mechanisms governing CSC driven malignancies.
    DOI:  https://doi.org/10.1038/s41375-022-01697-9
  7. Cold Spring Harb Perspect Med. 2022 Sep 19. pii: a041200. [Epub ahead of print]
    Biological Restraints on Indefinite Survival.
    Jan Vijg, Steven N Austad.
      Multiple observations that organismal life span can be extended by nutritional, genetic, or pharmacological intervention has raised the prospect of transforming medicine with the goal of slowing, stopping, or even reversing age-associated disease and maintaining or restoring health and resilience in the increasing numbers of elderly across the world. The potential for such an enterprise is supported in theory by plant and animal models of negligible senescence, most notably the small, freshwater organism Hydra spp. The existence of some very long-lived species, including bowhead whale, Greenland shark, and giant tortoises, suggests that increased healthy life spans in humans, significantly higher than the current known maximum life span of about 120 years, may be possible. Here we discuss the biological restraints on human life extension based on the evolutionary basis of aging and our current genetic and molecular insights into the processes responsible for age-related loss of function and increased disease risk.
    DOI:  https://doi.org/10.1101/cshperspect.a041200
  8. Int J Environ Res Public Health. 2022 Sep 10. pii: 11404. [Epub ahead of print]19(18):
    Methods for Successful Aging: An Aesthetics-Oriented Perspective Derived from Richard Shusterman's Somaesthetics.
    Yi-Huang Shih.
      This study explored Richard Shusterman's somaesthetics to understand the rationale for his view on enhancing the body experience of older adults and increasing their participation in art; it also examined methods or successful aging to enhance the theoretical foundation for educational gerontology. Accordingly, the research objectives were to (1) analyze the definition of successful aging; (2) clarify the role of body experience and participation in art in promoting successful aging among older adults; (3) explore and discuss Shusterman's somaesthetics; and (4) explore methods for successful aging derived from Shusterman's somaesthetics. This study mainly explored educational philosophy by collecting, reading, analyzing, logically reviewing, and interpreting the literature on this topic. During this exploration, methods for successful aging were reviewed. The findings are as follows: (1) shifting focus of successful aging to the bodies of older adults; (2) cultivating the body consciousness of older adults enables them to understand themselves and pursue virtue, happiness, and justice; (3) popular art can be integrated to promote the aesthetic ability of older adults and encourage their physical participation in the aesthetic process; (4) older adult education should cultivate the somaesthetic sensitivity of older adults; (5) older adult education should incorporate the physical training of older adults to help them enhance their self-cultivation and care for their body, cultivate virtue, and live a better life; and (6) older adult education should integrate the body and mind of older adults.
    Keywords:  Richard Shusterman; older adults; somaesthetics; successful aging
    DOI:  https://doi.org/10.3390/ijerph191811404
  9. Biol Futur. 2022 Sep 21.
    Biologia Futura: four questions about ageing and the future of relevant animal models.
    Enikő Kubinyi.
      Understanding how active and healthy ageing can be achieved is one of the most relevant global problems. In this review, I use the "Four questions" framework of Tinbergen to investigate how ageing works, how it might contribute to the survival of species, how it develops during the lifetime of (human) individuals and how it evolved. The focus of ageing research is usually on losses, although trajectories in later life show heterogeneity and many individuals experience healthy ageing. In humans, mild changes in cognition might be a typical part of ageing, but deficits are a sign of pathology. The ageing of the world's populations, and relatedly, the growing number of pathologically ageing people, is one of the major global problems. Animal models can help to understand the intrinsic and extrinsic factors contributing to ageing.
    Keywords:  Adaptation; Ageing; Animal models; Dementia; Evolution; Mechanism; Ontogeny; Post-fertility lifespan
    DOI:  https://doi.org/10.1007/s42977-022-00135-2
  10. Int Psychogeriatr. 2022 Sep 19. 1-7
    The Benefits of a Sense of Purpose in Life for Healthier Cognitive Aging.
    Angelina R Sutin, Martina Luchetti, Antonio Terracciano.
      
    DOI:  https://doi.org/10.1017/S1041610222000837
  11. Mol Metab. 2022 Sep 16. pii: S2212-8778(22)00170-3. [Epub ahead of print] 101601
    Targeting cellular senescence in metabolic disease.
    Allyson K Palmer, Tamar Tchkonia, James L Kirkland.
      Cellular senescence is a cell fate involving cell cycle arrest, resistance against apoptosis, and the development of a secretome that can be pro-inflammatory. In aging and obesity, senescent cells accumulate in many tissues, including adipose tissue, brain, kidney, pancreas, and liver. These senescent cells and their downstream effects appear to perpetuate inflammation and have been implicated in the pathogenesis of metabolic dysfunction. Senescent cells are cleared in part by the immune system, a process that is diminished in obesity and aging, likely due in part to senescence of immune cells themselves. Targeting senescent cells or their products improves metabolic function in both aging and in animal models of obesity. Novel therapeutics to target senescent cells are on the horizon and are currently being investigated in clinical trials in humans for multiple diseases. Early evidence suggests that senolytic drugs, which transiently disarm the anti-apoptotic defenses of pro-inflammatory senescent cells, are effective in causing depletion of senescent cells in humans. Senescence-targeting therapeutics, including senolytic drugs and strategies to increase immune clearance of senescent cells, hold significant promise for treating metabolic dysfunction in multiple tissues and disease states.
    Keywords:  Adipose; Aging; Cellular senescence; Obesity; Senolytics
    DOI:  https://doi.org/10.1016/j.molmet.2022.101601
  12. Int J Mol Sci. 2022 Sep 09. pii: 10443. [Epub ahead of print]23(18):
    Circular RNAs Involved in the Regulation of the Age-Related Pathways.
    Siqi Wang, Feng Xiao, Jiamei Li, Xiaolan Fan, Zhi He, Taiming Yan, Mingyao Yang, Deying Yang.
      Circular RNAs (circRNAs) are a class of covalently circular noncoding RNAs that have been extensively studied in recent years. Aging is a process related to functional decline that is regulated by signal transduction. An increasing number of studies suggest that circRNAs can regulate aging and multiple age-related diseases through their involvement in age-related signaling pathways. CircRNAs perform several biological functions, such as acting as miRNA sponges, directly interacting with proteins, and regulating transcription and translation to proteins or peptides. Herein, we summarize research progress on the biological functions of circRNAs in seven main age-related signaling pathways, namely, the insulin-insulin-like, PI3K-AKT, mTOR, AMPK, FOXO, p53, and NF-κB signaling pathways. In these pathways, circRNAs mainly function as miRNA sponges. In this review, we suggest that circRNAs are widely involved in the regulation of the main age-related pathways and are potential biomarkers for aging and age-related diseases.
    Keywords:  age-related pathway; aging; circRNAs; regulatory roles
    DOI:  https://doi.org/10.3390/ijms231810443
  13. Mol Oncol. 2022 Sep;16(18): 3213-3219
    The role of aging in cancer.
    Aaron Havas, Shanshan Yin, P D Adams.
      Many cancers show an increase in incidence with age, and age is the biggest single risk factor for many cancers. However, the molecular basis of this relationship is poorly understood. Through a collection of review articles, our thematic issue discusses the link between aging and cancer in aspects including somatic mutations, proteostasis, mitochondria, metabolism, senescence, epigenetic regulation, immune regulation, DNA damage, and telomere function.
    DOI:  https://doi.org/10.1002/1878-0261.13302
  14. Cell Tissue Res. 2022 Sep 21.
    Tafazzin deficiency attenuates anti-cluster of differentiation 40 and interleukin-4 activation of mouse B lymphocytes.
    Hana M Zegallai, Ejlal Abu-El-Rub, Edgard M Mejia, Genevieve C Sparagna, Laura K Cole, Aaron J Marshall, Grant M Hatch.
      Barth syndrome (BTHS) is a rare X-linked genetic disease caused by mutations in TAFAZZIN. The tafazzin (Taz) protein is a cardiolipin remodeling enzyme required for maintaining mitochondrial function. Patients with BTHS exhibit impaired mitochondrial respiratory chain and metabolic function and are susceptible to serious infections. B lymphocytes (B cells) play a vital role in humoral immunity required to eradicate circulating antigens from pathogens. Intact mitochondrial respiration is required for proper B-cell function. We investigated whether Taz deficiency in mouse B cells altered their response to activation by anti-cluster of differentiation 40 (anti-CD40) + interleukin-4 (IL-4). B cells were isolated from 3-4-month-old wild type (WT) or tafazzin knockdown (TazKD) mice and were stimulated with anti-CD40 + IL-4 for 24 h and cellular bioenergetics, surface marker expression, proliferation, antibody production, and proteasome and immunoproteasome activities determined. TazKD B cells exhibited reduced mRNA expression of Taz, lowered levels of cardiolipin, and impairment in both oxidative phosphorylation and glycolysis compared to WT B cells. In addition, anti-CD40 + IL-4 stimulated TazKD B cells expressed lower levels of the immunogenic surface markers, cluster of differentiation 86 (CD86) and cluster of differentiation 69 (CD69), exhibited a lower proliferation rate, reduced production of immunoglobulin M and immunoglobulin G, and reduced proteasome and immunoproteasome proteolytic activities compared to WT B cells stimulated with anti-CD40 + IL-4. The results indicate that Taz is required to support T-cell-dependent signaling activation of mouse B cells.
    Keywords:  B lymphocytes; Barth Syndrome; Cardiolipin; Mitochondria; T cell signaling; Tafazzin
    DOI:  https://doi.org/10.1007/s00441-022-03692-z
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