bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022‒02‒13
23 papers selected by
Ayesh Seneviratne
University of Toronto
  1. Caloric restriction has a new player.
  2. Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology.
  3. Mitochondrial and metabolic dysfunction in ageing and age-related diseases.
  4. Association between a lifestyle-based healthy heart score and risk of frailty in older women: a cohort study.
  5. Shared genetic and epigenetic changes link aging and cancer.
  6. Frailty prevalence and its associations in a subacute geriatric ward in Singapore.
  7. Exploring the Relationships Between Four Aging Ideals: A Bibliometric Study.
  8. BNT162b2 Vaccine Booster and Covid-19 Mortality. Reply.
  9. Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19.
  10. Measurement of neutral ceramidase activity in vitro and in vivo.
  11. Impact of the Cancer and Aging Research Group score and treatment intensity on survival and toxicity outcomes in older adults with advanced noncolorectal gastrointestinal cancers.
  12. Inflammation and Myeloid Cells in Cancer Progression and Metastasis.
  13. Well-being, food habits, and lifestyle for longevity. Preliminary evidence from the sardinian centenarians and long-lived people of the Blue Zone.
  14. Telomeres, aging, and cancer: the big picture.
  15. Frailty and Disability: Predictors or Outcomes or Both in Post COVID-19.
  16. My lesson from successful scientists: success can be learnt.
  17. BNT162b2 Vaccine Booster and Covid-19 Mortality.
  18. BNT162b2 Vaccine Booster and Covid-19 Mortality.
  19. Tracking COVID-19 infections: time for change.
  20. A Pernicious Cycle Affecting Premalignant Stem Cells.
  21. Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling.
  22. The ABCD of the comprehensive geriatric assessment.
  23. Srebf1c preserves hematopoietic stem cell function and survival as a switch of mitochondrial metabolism.
  1. Science. 2022 Feb 11. 375(6581): 620-621
    Caloric restriction has a new player.
    Timothy W Rhoads, Rozalyn M Anderson.
      Reverse translation of a human caloric restriction trial finds an immunometabolic regulator.
    DOI:  https://doi.org/10.1126/science.abn6576
  2. Nat Aging. 2021 Sep;1(9): 760-768
    Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology.
    Maxime J Derisbourg, Matías D Hartman, Martin S Denzel.
      Healthy aging requires the coordination of numerous stress signaling pathways that converge on the protein homeostasis network. The Integrated Stress Response (ISR) is activated by diverse stimuli, leading to phosphorylation of the eukaryotic translation initiation factor elF2 in its α-subunit. Under replete conditions, elF2 orchestrates 5' cap-dependent mRNA translation and is thus responsible for general protein synthesis. elF2α phosphorylation, the key event of the ISR, reduces global mRNA translation while enhancing the expression of a signature set of stress response genes. Despite the critical role of protein quality control in healthy aging and in numerous longevity pathways, the role of the ISR in longevity remains largely unexplored. ISR activity increases with age, suggesting a potential link with the aging process. Although decreased protein biosynthesis, which occurs during ISR activation, have been linked to lifespan extension, recent data show that lifespan is limited by the ISR as its inhibition extends survival in nematodes and enhances cognitive function in aged mice. Here we survey how aging affects the ISR, the role of the ISR in modulating aging, and pharmacological interventions to tune the ISR. Finally, we will explore the ISR as a plausible target for clinical interventions in aging and age-related disease.
    DOI:  https://doi.org/10.1038/s43587-021-00112-9
  3. Nat Rev Endocrinol. 2022 Feb 10.
    Mitochondrial and metabolic dysfunction in ageing and age-related diseases.
    João A Amorim, Giuseppe Coppotelli, Anabela P Rolo, Carlos M Palmeira, Jaime M Ross, David A Sinclair.
      Organismal ageing is accompanied by progressive loss of cellular function and systemic deterioration of multiple tissues, leading to impaired function and increased vulnerability to death. Mitochondria have become recognized not merely as being energy suppliers but also as having an essential role in the development of diseases associated with ageing, such as neurodegenerative and cardiovascular diseases. A growing body of evidence suggests that ageing and age-related diseases are tightly related to an energy supply and demand imbalance, which might be alleviated by a variety of interventions, including physical activity and calorie restriction, as well as naturally occurring molecules targeting conserved longevity pathways. Here, we review key historical advances and progress from the past few years in our understanding of the role of mitochondria in ageing and age-related metabolic diseases. We also highlight emerging scientific innovations using mitochondria-targeted therapeutic approaches.
    DOI:  https://doi.org/10.1038/s41574-021-00626-7
  4. Age Ageing. 2022 Feb 02. pii: afab268. [Epub ahead of print]51(2):
    Association between a lifestyle-based healthy heart score and risk of frailty in older women: a cohort study.
    Mercedes Sotos-Prieto, Ellen A Struijk, Teresa T Fung, Eric B Rimm, Fernando Rodriguez-Artalejo, Walter C Willett, Frank B Hu, Esther Lopez-Garcia.
      BACKGROUND: Evidence on the comprehensive role of lifestyle in frailty risk is scarce. To assess the association between a lifestyle-based Healthy Heart Score (HHS), which estimates the 20-year risk of cardiovascular disease (CVD), and risk of frailty among older women.METHODS: Prospective cohort study in 121,700 nurses from the USA participating at the Nurses' Health Study. This study included 68,416 women aged ≥60 year with a follow-up from 1990 to 2014. The HHS was computed using the gender-specific beta-coefficients of the nine lifestyle factors, including current smoking, high body mass index, low physical activity, lack of moderate alcohol intake and unhealthy diet. Frailty incidence was assessed every 4 years from 1992 to 2014 as having ≥3 of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses and weight loss ≥5%.
    RESULTS: During 22 years of follow-up, 11,041 total incident cases of frailty were ascertained. Compared to women in the lowest quintile of the HHS (lowest estimated CVD risk), the multivariable-adjusted hazard ratio of frailty across quintiles was: Q2:1.67 (95% confidence interval 1.53, 1.82); Q3: 2.34 (2.15, 2.53); Q4: 3.54 (3.28, 3.83) and Q5: 5.92 (5.48, 6.38); P-trend > 0.001. Results were consistent for each frailty criterion, among participants with 0 frailty criteria at baseline, when using only baseline exposure or in 6-year-, 10-year- and 14-year-exposure lagged analyses, and after excluding participants with diabetes and CVD at baseline.
    CONCLUSIONS: The HHS, based on a set of modifiable-lifestyle factors, is strongly associated with risk of frailty in older women.
    Keywords:  Nurses’ Health; Older people; cardiovascular disease (CVD) risk prediction; frailty; lifestyle; older adults
    DOI:  https://doi.org/10.1093/ageing/afab268
  5. Trends Cell Biol. 2022 Feb 07. pii: S0962-8924(22)00005-8. [Epub ahead of print]
    Shared genetic and epigenetic changes link aging and cancer.
    Daniel J Zabransky, Elizabeth M Jaffee, Ashani T Weeraratna.
      Aging is a universal biological process that increases the risk of multiple diseases including cancer. Growing evidence shows that alterations in the genome and epigenome, driven by similar mechanisms, are found in both aged cells and cancer cells. In this review, we detail the genetic and epigenetic changes associated with normal aging and the mechanisms responsible for these changes. By highlighting genetic and epigenetic alterations in the context of tumorigenesis, cancer progression, and the aging tumor microenvironment, we examine the possible impacts of the normal aging process on malignant transformation. Finally, we examine the implications of age-related genetic and epigenetic alterations in both tumors and patients for the treatment of cancer.
    Keywords:  aging; cancer; epigenetics; genetics; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.tcb.2022.01.004
  6. Singapore Med J. 2022 Feb 10.
    Frailty prevalence and its associations in a subacute geriatric ward in Singapore.
    Christine Yuanxin Chen, Thulasi Chandran, Vivian Cantiller Barrera, Rachelle Tumboko Tan-Pantanao, Tanya Joy Zapata Quicho, Zin Tun Thant, Kiat Sern Goh.
      INTRODUCTION: Our aim was to study the prevalence of frailty and its associated factors in a subacute geriatric ward.METHODS: This was a cross-sectional study of 167 participants between June 2018 and June 2019. Baseline demographics and participants' Mini Nutritional Assessment, Geriatric Depression Scale, Mini Mental State Examination, Charlson's Comorbidity Index and LACE index scores were obtained. Functional measurements such as modified Barthel's Index scores and hand grip strength (HGS) were taken. Frailty was assessed using the Clinical Frailty Scale (CFS) and the FRAIL scale. Data on history of healthcare utilisation, medications, length of stay, selected blood investigations and presence of geriatric syndromes was also collected.
    RESULTS: The prevalence of pre-frailty (CFS 4) and frailty (CFS ≥ 5) was 16.2% and 63.4%, respectively. There were significant associations between CFS and age (pre-frail vs. non-frail: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.25, p = 0.006; frail vs. non-frail: OR 1.08, 95% CI 1.01-1.15, p = 0.021), HGS at discharge (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, p = 0.025), serum albumin (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, p = 0.035) and the presence of urinary incontinence (frail vs. non-frail: OR 3.03, 95% CI 1.19-7.77, p = 0.021).
    CONCLUSION: Frailty is highly prevalent in the subacute geriatric setting and has many associated factors. In this study, independent factors associated with frailty were age, HGS at discharge, serum albumin and urinary incontinence. This has implications for future resource allocation for frail older inpatients and may help direct further research to study the effectiveness of frailty-targeted interventions.
    Keywords:  albumin; frailty; hand grip strength; subacute; urinary incontinence
    DOI:  https://doi.org/10.11622/smedj.2022020
  7. Front Public Health. 2021 ;9 762591
    Exploring the Relationships Between Four Aging Ideals: A Bibliometric Study.
    Ka Lin, Yumei Ning, Ayesha Mumtaz, Hua Li.
      When examining research articles on the aging strategies, four ideals (i.e., successful aging, healthy aging, productive aging and active aging) could be explored by conducting bibliometric analyses. For the literature analysis, general information on the four aging ideals was understood through visualization analysis; the intellectual base and research hotspots were intuitively observed. CiteSpace was used as the method to conduct the co-occurrence analysis of keywords in order to obtain research trends and cutting-edge knowledge in the field of aging-related policies. Subsequently, the study revealed the nature of the link between these four aging ideals and disclosed the connection between their fundamental principles. The study ultimately enhanced the understanding of the diverse contexts that have impacted the way in which these ideals influence policy, which has caused dissimilar strategies for policy development. The study also extended the discussion of the definitions of and relationships between these four ideals with the goal of identifying new directions for aging-related practice and providing innovative insights and references for investigators.
    Keywords:  CiteSpace; aging studies; bibliometric; elderly care; health care; social policy
    DOI:  https://doi.org/10.3389/fpubh.2021.762591
  8. N Engl J Med. 2022 Feb 09. pii: 10.1056/NEJMc2120044#sa3. [Epub ahead of print]
    BNT162b2 Vaccine Booster and Covid-19 Mortality. Reply.
    Ronen Arbel, Ruslan Sergienko, Ariel Hammerman.
      
    DOI:  https://doi.org/10.1056/NEJMc2120044
  9. Front Aging. 2021 Jul;pii: 695218. [Epub ahead of print]2
    Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19.
    Alan Landay, Jenna Bartley, Dishary Banerjee, Geneva Hargis, Laura Haynes, Ali Keshavarzian, Chia-Ling Kuo, Oh Sung Kwon, Sheng Li, Shuzhao Li, Julia Oh, Ibrahim Tarik Ozbolat, Duygu Ucar, Ming Xu, Xudong Yao, Derya Unutmaz, George A Kuchel.
      Aging has emerged as the greatest and most prevalent risk factor for the development of severe COVID-19 infection and death following exposure to the SARS-CoV-2 virus. The presence of multiple co-existing chronic diseases and conditions of aging further enhances this risk. Biological aging not only enhances the risk of chronic diseases, but the presence of such conditions further accelerates varied biological processes or "hallmarks" implicated in aging. Given growing evidence that it is possible to slow the rate of many biological aging processes using pharmacological compounds has led to the proposal that such geroscience-guided interventions may help enhance immune resilience and improve outcomes in the face of SARS-CoV-2 infection. Our review of the literature indicates that most, if not all, hallmarks of aging may contribute to the enhanced COVID-19 vulnerability seen in frail older adults. Moreover, varied biological mechanisms implicated in aging do not function in isolation from each other, and exhibit intricate effects on each other. With all of these considerations in mind, we highlight limitations of current strategies mostly focused on individual single mechanisms, and we propose an approach which is far more multidisciplinary and systems-based emphasizing network topology of biological aging and geroscience-guided approaches to COVID-19.
    Keywords:  Aging; COVID-19; Frailty; Geroscience; Immunology of Aging
    DOI:  https://doi.org/10.3389/fragi.2021.695218
  10. Anal Biochem. 2022 Feb 05. pii: S0003-2697(22)00032-X. [Epub ahead of print] 114577
    Measurement of neutral ceramidase activity in vitro and in vivo.
    Michael Simoes, Amalia Saleh, Yong-Mi Choi, Michael V Airola, John D Haley, Nicolas Coant.
      Neutral ceramidase is a hydrolase of ceramide that has been implicated in multiple biologic processes, including inflammation and oncogenesis. Ceramides and other sphingolipids, belong to a family of N-acyl linked lipids that are biologically active in signaling, despite their limited structural functions. Ceramides are generally pro-apoptotic, while sphingosine and sphingosine-1-phosphate (S1P) exert proliferative and pro-oncogenic effects. Ceramidases are important regulators of ceramide levels that hydrolyze ceramide to sphingosine. Thus, ceramidase inhibition significantly increases the quantities of ceramide and its associated signaling. To better understand the function of ceramide, biochemical and cellular assays for enzymatic activity were developed and validated to identify inhibitors of human neutral ceramidase (nCDase). Here we review the measurement of nCDase activity both in vitro and in vivo.
    Keywords:  Ceramides; Neutral ceramidase; Neutral ceramidase enzymatic assays
    DOI:  https://doi.org/10.1016/j.ab.2022.114577
  11. Cancer. 2022 Feb 11.
    Impact of the Cancer and Aging Research Group score and treatment intensity on survival and toxicity outcomes in older adults with advanced noncolorectal gastrointestinal cancers.
    Tomohiro F Nishijima, Allison M Deal, Grant R Williams, Hanna K Sanoff, Kirsten A Nyrop, Hyman B Muss.
      BACKGROUND: Little is known regarding the predictive value of the Cancer and Aging Research Group (CARG) score, a validated chemotherapy toxicity prediction tool for older adults with cancer, for survival outcomes.METHODS: This was a prospective observational study of patients ≥65 years old receiving first-line chemotherapy for advanced noncolorectal gastrointestinal cancer for which combination chemotherapy is the standard of care. Overall survival (OS), time to treatment failure (TTF), which was defined as the time from the start of first-line chemotherapy to the discontinuation of first-line chemotherapy for any reason, and toxicity were compared in 4 groups of patients: 1) non-high-risk (nHR) CARG score (<10) and standard-intensity therapy (ST), 2) nHR score and reduced-intensity therapy (RT), 3) high-risk (HR) CARG score (≥10) and ST, and 4) HR score and RT.
    RESULTS: Fifty patients (median age, 71 years) were enrolled. The median OS in months was 19.7 in nHR/ST (n = 19) group, 12.7 in nHR/RT (n = 9) group, 4.5 in HR/ST (n = 12) group, and 3.9 in HR/RT (n = 10) group (log-rank test, P = .005). The median TTF in months was 9.1 in nHR/ST group, 2.5 in nHR/RT group, 2.3 in HR/ST group, and 3.0 in HR/RT group (log-rank test, P = .04). The CARG-score category was prognostic of OS (HR, 3.04; 95% confidence interval [CI], 1.59-5.83, P = .001) and TTF (HR, 2.60; 95% CI, 1.31-5.20, P = .007). The incidence of grade 3-5 toxicity was 68% in nHR/ST group, 33% in nHR/RT group, 92% in HR/ST group, and 70% in HR/RT group (Fisher exact test, P = .048).
    CONCLUSIONS: Risk-adapted chemotherapy based on the CARG-score may improve treatment outcomes.
    Keywords:  CARG; Cancer and Aging Research Group toxicity score; adverse events; older adults with cancer; overall survival; time to treatment failure
    DOI:  https://doi.org/10.1002/cncr.34135
  12. Front Cell Dev Biol. 2021 ;9 759691
    Inflammation and Myeloid Cells in Cancer Progression and Metastasis.
    Jenying Deng, Jason B Fleming.
      To date, the most immunotherapy drugs act upon T cell surface proteins to promote tumoricidal T cell activity. However, this approach has to date been unsuccessful in certain solid tumor types including pancreatic, prostate cancer and glioblastoma. Myeloid-related innate immunity can promote tumor progression through direct and indirect effects on T cell activity; improved understanding of this field may provide another therapeutic avenue for patients with these tumors. Myeloid cells can differentiate into both pro-inflammatory and anti-inflammatory mature form depending upon the microenvironment. Most cancer type exhibit oncogenic activating point mutations (ex. P53 and KRAS) that trigger cytokines production. In addition, tumor environment (ex. Collagen, Hypoxia, and adenosine) also regulated inflammatory signaling cascade. Both the intrinsic and extrinsic factor driving the tumor immune microenvironment and regulating the differentiation and function of myeloid cells, T cells activity and tumor progression. In this review, we will discuss the relationship between cancer cells and myeloid cells-mediated tumor immune microenvironment to promote cancer progression and immunotherapeutic resistance. Furthermore, we will describe how cytokines and chemokines produced by cancer cells influence myeloid cells within immunosuppressive environment. Finally, we will comment on the development of immunotherapeutic strategies with respect to myeloid-related innate immunity.
    Keywords:  MDSCs; cancer; inflammation; macrophages; myeloid cells; neutrophils
    DOI:  https://doi.org/10.3389/fcell.2021.759691
  13. Psychol Health Med. 2022 Feb 06. 1-6
    Well-being, food habits, and lifestyle for longevity. Preliminary evidence from the sardinian centenarians and long-lived people of the Blue Zone.
    Maria Chiara Fastame.
      Lifestyle, physical, and mental health impact successful aging. However, at present, extensive literature about the interplay among perceived mental and physical health, lifestyle, and food intake in long-lived people residing in areas of exceptional longevity is lacking. This study was mainly aimed at examining the relationships among self-assessed life satisfaction, physical health, lifestyle, and food intake in the last two decades of life. A further goal was to investigate the impact of age-related factors on the above variables. The recruitment was mainly conducted in the Sardinian Blue Zone, a well-documented area of exceptional longevity in Sardinia, an Italian Island located in the Mediterranean Sea. Twenty-nine octogenarians (Mage = 83.9 years, SD = 2.7) and 28 gender-matched long-lived (Mage = 97.6 years, SD = 7.9) community-dwellers took voluntarily part in the study. Each participant individually completed a battery of tasks assessing their global cognitive efficiency, life satisfaction, lifestyle, food intake, and perceived physical health. The results highlighted that life satisfaction was significantly associated with time spent on outdoor leisure activities (r = .314, p = .026), perceived physical health (r = .459, p = .001), and carbohydrate intake (r = .333, p = .021). Moreover, the octogenarians and long-lived groups reported similar levels of life satisfaction (t(56) = .573, p = .569, Cohen's d = .164). In conclusion, healthy nutrition habits and a physically active lifestyle boosting mental and physical health are crucial for promoting optimal aging.
    Keywords:  Successful aging; life satisfaction; lifestyle; longevity; nutrition
    DOI:  https://doi.org/10.1080/13548506.2022.2038384
  14. Blood. 2022 Feb 10. 139(6): 813-821
    Telomeres, aging, and cancer: the big picture.
    Peter M Lansdorp.
      The role of telomeres in human health and disease is yet to be fully understood. The limitations of mouse models for the study of human telomere biology and difficulties in accurately measuring the length of telomere repeats in chromosomes and cells have diverted attention from many important and relevant observations. The goal of this perspective is to summarize some of these observations and to discuss the antagonistic role of telomere loss in aging and cancer in the context of developmental biology, cell turnover, and evolution. It is proposed that both damage to DNA and replicative loss of telomeric DNA contribute to aging in humans, with the differences in leukocyte telomere length between humans being linked to the risk of developing specific diseases. These ideas are captured in the Telomere Erosion in Disposable Soma theory of aging proposed herein.
    DOI:  https://doi.org/10.1182/blood.2021014299
  15. Crit Care Med. 2022 Feb 08.
    Frailty and Disability: Predictors or Outcomes or Both in Post COVID-19.
    Patricia Anne O'Malley.
      
    DOI:  https://doi.org/10.1097/CCM.0000000000005502
  16. Nature. 2022 Feb 07.
    My lesson from successful scientists: success can be learnt.
    Ruth Gotian.
      
    DOI:  https://doi.org/10.1038/d41586-022-00354-6
  17. N Engl J Med. 2022 Feb 09. pii: 10.1056/NEJMc2120044#sa2. [Epub ahead of print]
    BNT162b2 Vaccine Booster and Covid-19 Mortality.
    Stefan Pilz.
      
    DOI:  https://doi.org/10.1056/NEJMc2120044
  18. N Engl J Med. 2022 Feb 09. pii: 10.1056/NEJMc2120044#sa1. [Epub ahead of print]
    BNT162b2 Vaccine Booster and Covid-19 Mortality.
    Thomas Rohban.
      
    DOI:  https://doi.org/10.1056/NEJMc2120044
  19. Nature. 2022 02;602(7896): 185
    Tracking COVID-19 infections: time for change.
    Natalie Dean.
      
    Keywords:  Epidemiology; Health care; Research management; SARS-CoV-2
    DOI:  https://doi.org/10.1038/d41586-022-00336-8
  20. N Engl J Med. 2022 Feb 10. 386(6): 596-598
    A Pernicious Cycle Affecting Premalignant Stem Cells.
    Nancy A Speck.
      
    DOI:  https://doi.org/10.1056/NEJMcibr2117528
  21. Geroscience. 2022 Feb 05.
    Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling.
    Tamas Kiss, Ádám Nyúl-Tóth, Rafal Gulej, Stefano Tarantini, Tamas Csipo, Peter Mukli, Anna Ungvari, Priya Balasubramanian, Andriy Yabluchanskiy, Zoltan Benyo, Shannon M Conley, Jonathan D Wren, Lori Garman, Derek M Huffman, Anna Csiszar, Zoltan Ungvari.
       Vascular aging has a central role in the pathogenesis of cardiovascular diseases contributing to increased mortality of older adults. There is increasing evidence that, in addition to the documented role of cell-autonomous mechanisms of aging, cell-nonautonomous mechanisms also play a critical role in the regulation of vascular aging processes. Our recent transcriptomic studies (Kiss T. et al. Geroscience. 2020;42(2):727-748) demonstrated that circulating anti-geronic factors from young blood promote vascular rejuvenation in aged mice. The present study was designed to expand upon the results of this study by testing the hypothesis that circulating pro-geronic factors also contribute to the genesis of vascular aging phenotypes. To test this hypothesis, through heterochronic parabiosis, we determined the extent to which shifts in the vascular transcriptome (RNA-seq) are modulated by the old systemic environment. We reanalyzed existing RNA-seq data, comparing the transcriptome in the aorta arch samples isolated from isochronic parabiont aged (20-month-old) C57BL/6 mice [A-(A); parabiosis for 8 weeks] and young isochronic parabiont (6-month-old) mice [Y-(Y)] and also assessing transcriptomic changes in the aortic arch in young (6-month-old) parabiont mice [Y-(A); heterochronic parabiosis for 8 weeks] induced by the presence of old blood derived from aged (20-month-old) parabionts. We identified 528 concordant genes whose expression levels differed in the aged phenotype and were shifted towards the aged phenotype by the presence of old blood in young Y-(A) animals. Among them, the expression of 221 concordant genes was unaffected by the presence of young blood in A-(Y) mice. GO enrichment analysis suggests that old blood-regulated genes may contribute to pathologic vascular remodeling. IPA Upstream Regulator analysis (performed to identify upstream transcriptional regulators that may contribute to the observed transcriptomic changes) suggests that the mechanism of action of pro-geronic factors present in old blood may include inhibition of pathways mediated by SRF (serum response factor), insulin-like growth factor-1 (IGF-1) and VEGF-A. In conclusion, relatively short-term exposure to old blood can accelerate vascular aging processes. Our findings provide additional evidence supporting the significant plasticity of vascular aging and the existence of circulating pro-geronic factors mediating pathological remodeling of the vascular smooth muscle cells and the extracellular matrix.
    Keywords:  Aging; Aneurysm; Aorta; Atherosclerosis; Heterochronic parabiosis; Transcriptome; Vascular aging
    DOI:  https://doi.org/10.1007/s11357-022-00519-1
  22. Med J Aust. 2022 Feb 10.
    The ABCD of the comprehensive geriatric assessment.
    Paven Kaur.
      
    DOI:  https://doi.org/10.5694/mja2.51407
  23. Stem Cell Reports. 2022 Feb 01. pii: S2213-6711(22)00055-8. [Epub ahead of print]
    Srebf1c preserves hematopoietic stem cell function and survival as a switch of mitochondrial metabolism.
    Yukai Lu, Zihao Zhang, Song Wang, Yan Qi, Fang Chen, Yang Xu, Mingqiang Shen, Mo Chen, Naicheng Chen, Lijing Yang, Shilei Chen, Fengchao Wang, Yongping Su, Mengjia Hu, Junping Wang.
      Mitochondria are fundamental but complex determinants for hematopoietic stem cell (HSC) maintenance. However, the factors involved in the regulation of mitochondrial metabolism in HSCs and the underlying mechanisms have not been fully elucidated. Here, we identify sterol regulatory element binding factor-1c (Srebf1c) as a key factor in maintaining HSC biology under both steady-state and stress conditions. Srebf1c knockout (Srebf1c-/-) mice display increased phenotypic HSCs and less HSC quiescence. In addition, Srebf1c deletion compromises the function and survival of HSCs in competitive transplantation or following chemotherapy and irradiation. Mechanistically, SREBF1c restrains the excessive activation of mammalian target of rapamycin (mTOR) signaling and mitochondrial metabolism in HSCs by regulating the expression of tuberous sclerosis complex 1 (Tsc1). Our study demonstrates that Srebf1c plays an important role in regulating HSC fate via the TSC1-mTOR-mitochondria axis.
    Keywords:  Srebf1c; TSC1; hematopoietic stem cell; mTOR; mitochondrial metabolism
    DOI:  https://doi.org/10.1016/j.stemcr.2022.01.011
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