bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022–10–16
seven papers selected by
Ayesh Seneviratne, Western University
  1. FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases.
  2. HSC derived fatty acid oxidation in steady state and stressed haematopoiesis.
  3. Clonal hematopoiesis of indeterminate potential: associations with heart failure incidence, clinical parameters and biomarkers.
  4. Adherence to the Mediterranean Diet and Incidence of Pre-Frailty and Frailty in Community-Dwelling Adults 70+: The 3-Year DO-HEALTH Study.
  5. Clonal hematopoiesis and cardiovascular disease in cancer patients and survivors.
  6. Frailty as a Predictor of Adverse Outcomes among Spanish Community-Dwelling Older Adults.
  7. Omicron boosters could arm you against variants that don't yet exist.
  1. Curr Mol Med. 2022 Oct 14.
    FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases.
    Zao-Shang Chang, Zhi-Ming He, Jing-Bo Xia.
      Aging is an inevitable risk factor for many diseases including cardiovascular diseases, neurodegenerative diseases, cancer, and diabetes. Investigation into the molecular mechanisms involved in aging and longevity will benefit the treatment of age-dependent diseases and the development of preventative medicine for aging-related diseases. Current evidence has revealed that FoxO3, encoding the transcription factor (FoxO) 3, a key transcription factor that integrates different stimuli in the intrinsic and extrinsic pathways and is involved in cell differentiation, protein homeostasis, stress resistance and stem cell status, plays a regulatory role in longevity and in age-related diseases. However, the precise mechanisms by which the FoxO3 transcription factor modulates aging and promotes longevity have been unclear until now. Here, we provide a brief overview of the mechanisms by which FoxO3 mediates signaling in pathways involved in aging and aging-related diseases, as well as the current knowledge on the role of the FoxO3 transcription factor in the human lifespan and its clinical prospects. Ultimately, we conclude that FoxO3 signaling pathways, including upstream and downstream molecules, may be underlying therapeutic targets in aging and age-related diseases.
    Keywords:  FoxO3; aging; aging-related diseases; longevity; mechanisms; pathways
    DOI:  https://doi.org/10.2174/1566524023666221014140817
  2. Exp Hematol. 2022 Oct 09. pii: S0301-472X(22)00704-4. [Epub ahead of print]
    HSC derived fatty acid oxidation in steady state and stressed haematopoiesis.
    Jayna J Mistry, Kristian Bowles, Stuart A Rushworth.
      Metabolism impacts all cellular functions and plays a fundamental role in physiology. Metabolic regulation in hematopoiesis is dynamically regulated under steady state and stress conditions. It is clear, that hematopoietic stem cells (HSCs) impose different energy demands and flexibility during maintenance compared to stressed conditions. However, the cellular and molecular mechanism underlying the metabolic regulation in HSCs remains poorly understand. In this review we focus on defining the role of fatty acid oxidation (FAO) in HSC. We will first review the existing literature describing FAO in HSCs under steady state hematopoiesis. Next, we will describe the models used to examine HSCs under stress conditions and finally, we will describe how infection causes a shift towards FAO in HSC and the impact of using this pathway has on emergency hematopoiesis.
    Keywords:  Mitochondria; Stem cell; b-oxidation; metabolism
    DOI:  https://doi.org/10.1016/j.exphem.2022.10.003
  3. Eur J Heart Fail. 2022 Oct 11.
    Clonal hematopoiesis of indeterminate potential: associations with heart failure incidence, clinical parameters and biomarkers.
    Canxia Shi, Joseph Pierre Aboumsallem, Navin Suthahar, Aniek O de Graaf, Joop H Jansen, Isabelle A van Zeventer, Valentina Bracun, Sanne de Wit, Elles M Screever, Pieter F van den Berg, Wouter C Meijers, Ron T Gansevoort, Stephan J L Bakker, Pim van der Harst, Herman H W Silljé, Gerwin Huls, Rudolf A de Boer.
       AIM: We aimed to analyze the association of clonal hematopoiesis of indeterminate potential (CHIP) with incident heart failure (HF) in a European population cohort.
    METHODS AND RESULTS: From the prospective Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort, we included all 374 participants with incident HF and selected 1:1 age- and sex-matched control subjects. Peripheral blood samples of 705 individuals were successfully analyzed by error-corrected next generation sequencing for acquired mutations at a variant allele frequency ≥2% in 27 driver genes. The median age of study population was 65 (interquartile range 58-70) and 35.6% were female. CHIP mutations positively correlated with age, smoking, hypertension and cardiovascular biomarkers including NT-proBNP and MR-proANP, but the frequency of CHIP was comparable in individuals with incident HF and in control participants (18.4% vs. 17.3%; P =0.69). In multivariable Cox-regression models, CHIP was not significantly associated with incident HF (HR 1.24, 95% CI 0.93-1.65; P =0.144). This association, however, was modified by age (P for CHIP-age interaction =0.002). Among people younger than 65 years, CHIP mutations were more frequently detected in the case cohort compared to the control cohort (14.2% vs. 5.8%; P =0.009), and were significantly associated with new-onset HF (HR 2.07, 95% CI 1.30-3.29; P =0.002).
    CONCLUSION: CHIP correlates with HF risk factors and biomarkers, and is associated with incident HF in subjects <65 years of age. This article is protected by copyright. All rights reserved.
    Keywords:  Biomarkers; CHIP; Clonal hematopoiesis; Heart failure; Risk factors
    DOI:  https://doi.org/10.1002/ejhf.2715
  4. Nutrients. 2022 Oct 06. pii: 4145. [Epub ahead of print]14(19):
    Adherence to the Mediterranean Diet and Incidence of Pre-Frailty and Frailty in Community-Dwelling Adults 70+: The 3-Year DO-HEALTH Study.
    Stephanie Gängler, Hanna Steiner, Michael Gagesch, Sophie Guyonnet, E John Orav, Arnold von Eckardstein, Walter C Willett, Heike A Bischoff-Ferrari.
      The Mediterranean diet has been associated with many health benefits. Therefore, we investigated whether the degree of adherence to the Mediterranean diet at baseline, or changes in adherence over time, were associated with the incidence of pre-frailty or frailty in generally healthy older adults. This study used the DO-HEALTH trial data. We evaluated Mediterranean diet adherence with Panagiotakos' MedDietScore at baseline and at 3-year follow-up; frailty was assessed annually with the Fried frailty phenotype. We used minimally and fully adjusted mixed logistic regression models to estimate the exposure-disease relationship. We included 1811 participants without frailty at baseline (mean age 74.7 years; 59.4% women). Baseline adherence, as reflected by the MedDietScore, was not associated with becoming pre-frail [OR(95%CI) = 0.93 (0.83-1.03) for five-point greater adherence] or frail [OR(95%CI) = 0.90 (0.73-1.12) for five points]. However, a five-point increase in the MedDietScore over three years was associated with lower odds of becoming pre-frail [OR(95%CI) = 0.77 (0.68-0.88)] and frail [OR(95%CI) = 0.77 (0.64-0.92)]. In generally healthy and active older adults, baseline adherence to the Mediterranean diet was not associated with the incidence of pre-frailty or frailty over a 3-year follow-up. However, improved adherence to the Mediterranean diet over time was associated with significantly lower odds of becoming pre-frail or frail.
    Keywords:  Mediterranean diet; aging; dietary patterns; frailty; inflammaging
    DOI:  https://doi.org/10.3390/nu14194145
  5. Thromb Res. 2022 May;pii: S0049-3848(21)00568-5. [Epub ahead of print]213 Suppl 1 S107-S112
    Clonal hematopoiesis and cardiovascular disease in cancer patients and survivors.
    José J Fuster.
      Cancer genomes have long been known to carry a high number of somatic mutations distributed across many genes. However, recent sequencing studies have unveiled that non-cancerous cells also carry a considerable number of somatic mutations, which are acquired continuously through the lifespan. Accordingly, the pathophysiological relevance of somatic mutagenesis beyond cancer has become a topic of intensive research. Human genetic studies and experiments in mice have shown that some somatic mutations in the hematopoietic system provide a competitive advantage to the mutant cell and allow its clonal expansion. This phenomenon, termed clonal hematopoiesis, is typically driven by mutations in known oncogenes and tumor suppressor genes, and it is associated with a higher risk of hematological malignancies. Unexpectedly, accumulating genetic and experimental evidence strongly suggest that clonal hematopoiesis, at least when driven by certain mutations, also contributes causally to the development of cardiovascular disease and, therefore, represents a new cardiovascular risk factor. While clonal hematopoiesis is relatively common in healthy individuals, especially among the elderly, it is particularly frequent in cancer patients and survivors. Hence, it has emerged as a candidate contributor to the increased risk of cardiovascular complications in cancer patients. This review summarizes our current understanding of the connection between clonal hematopoiesis and cardiovascular disease, with a special focus on the available evidence linking clonal hematopoiesis to cardiovascular disorders that are frequent in cancer patients and survivors.
    Keywords:  CHIP; Inflammation; JAK2; PPM1D; TET2; TP53
    DOI:  https://doi.org/10.1016/j.thromres.2021.12.009
  6. Int J Environ Res Public Health. 2022 Oct 05. pii: 12756. [Epub ahead of print]19(19):
    Frailty as a Predictor of Adverse Outcomes among Spanish Community-Dwelling Older Adults.
    Ascensión Doñate-Martínez, Tamara Alhambra-Borrás, Estrella Durá-Ferrandis.
      Spain is one of the European countries with the oldest populations. The prevalence of frailty among Spanish older people ranges from 8.4 to 29.4% and currently, is one of the most relevant public health challenges. The Tilburg Frailty indicator (TFI) has been widely used in the community and in healthcare settings for assessing frailty. The objective of this study is to evaluate the predictive performance of the TFI for several adverse outcomes among Spanish community-dwelling older adults. The predictive performance was tested through linear regression analyses and receiver operating characteristics (ROC) curves. A total of 552 Spanish older adults composed the study sample. Participants were assessed at baseline and after 6 months. Main results showed that frailty was strongly and significantly correlated with disability, physical health, mental health and falls efficacy. The TFI score predicted most of these adverse outcomes. The ROC analyses confirmed the acceptable predictive performance of the total frailty. This study provides new evidence confirming that the TFI is a valid tool to predict several adverse outcomes in Spanish older adults, which may allow professionals to plan and activate health and social care resources to support frail patients' needs.
    Keywords:  disability; falls; frailty; predictive performance; quality of life; use of healthcare resources
    DOI:  https://doi.org/10.3390/ijerph191912756
  7. Nature. 2022 Oct 14.
    Omicron boosters could arm you against variants that don't yet exist.
    Sara Reardon.
      
    Keywords:  Immunology; Infection; Public health; SARS-CoV-2; Vaccines
    DOI:  https://doi.org/10.1038/d41586-022-03119-3
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