bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024–03–31
twelve papers selected by
Ayesh Seneviratne, Western University
  1. Partial reprogramming of the mammalian brain.
  2. Clonal Hematopoiesis: The Emergent CVD Risk Factor.
  3. Anti-ageing antibodies revive the immune system.
  4. Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche.
  5. Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity.
  6. Intensive blood pressure control does not lower risk of cardiac conduction system diseases.
  7. Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions.
  8. Pregnancy advances your 'biological' age - but giving birth turns it back.
  9. Clonal haematopoiesis and AKI.
  10. Advancements in personalized stem cell models for aging-related neurodegenerative disorders.
  11. TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models.
  12. Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.
  1. Nat Aging. 2024 Mar 29.
    Partial reprogramming of the mammalian brain.
    Niels C Asmussen, Marissa J Schafer.
      
    DOI:  https://doi.org/10.1038/s43587-024-00596-1
  2. Arterioscler Thromb Vasc Biol. 2024 Apr;44(4): 768-771
    Clonal Hematopoiesis: The Emergent CVD Risk Factor.
    Jesse D Cochran, Kenneth Walsh.
      
    Keywords:  biomarkers; cardiovascular diseases; clonal hematopoiesis; precision medicine; prognosis
    DOI:  https://doi.org/10.1161/ATVBAHA.123.319562
  3. Nature. 2024 Apr;628(8006): 43-45
    Anti-ageing antibodies revive the immune system.
    Yasar Arfat T Kasu, Robert A J Signer.
      
    Keywords:  Ageing; Immunology; Therapeutics
    DOI:  https://doi.org/10.1038/d41586-024-00680-x
  4. Nat Aging. 2024 Mar 29.
    Restoration of neuronal progenitors by partial reprogramming in the aged neurogenic niche.
    Lucy Xu, Julliana Ramirez-Matias, Max Hauptschein, Eric D Sun, Judith C Lunger, Matthew T Buckley, Anne Brunet.
      Partial reprogramming (pulsed expression of reprogramming transcription factors) improves the function of several tissues in old mice. However, it remains largely unknown how partial reprogramming impacts the old brain. Here we use single-cell transcriptomics to systematically examine how partial reprogramming influences the subventricular zone neurogenic niche in aged mouse brains. Whole-body partial reprogramming mainly improves neuroblasts (cells committed to give rise to new neurons) in the old neurogenic niche, restoring neuroblast proportion to more youthful levels. Interestingly, targeting partial reprogramming specifically to the neurogenic niche also boosts the proportion of neuroblasts and their precursors (neural stem cells) in old mice and improves several molecular signatures of aging, suggesting that the beneficial effects of reprogramming are niche intrinsic. In old neural stem cell cultures, partial reprogramming cell autonomously restores the proportion of neuroblasts during differentiation and blunts some age-related transcriptomic changes. Importantly, partial reprogramming improves the production of new neurons in vitro and in old brains. Our work suggests that partial reprogramming could be used to rejuvenate the neurogenic niche and counter brain decline in old individuals.
    DOI:  https://doi.org/10.1038/s43587-024-00594-3
  5. Nature. 2024 Mar 27.
    Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity.
    Jason B Ross, Lara M Myers, Joseph J Noh, Madison M Collins, Aaron B Carmody, Ronald J Messer, Erica Dhuey, Kim J Hasenkrug, Irving L Weissman.
      Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.
    DOI:  https://doi.org/10.1038/s41586-024-07238-x
  6. Nat Aging. 2024 Mar 22.
    Intensive blood pressure control does not lower risk of cardiac conduction system diseases.
      
    DOI:  https://doi.org/10.1038/s43587-024-00605-3
  7. Int J Mol Sci. 2024 Mar 14. pii: 3319. [Epub ahead of print]25(6):
    Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions.
    Shuo Wang, Najla El Jurdi, Bharat Thyagarajan, Anna Prizment, Anne H Blaes.
      The population of cancer survivors has markedly increased due to the rapid improvements in cancer treatment. However, cancer survivors experience accelerated aging, which leads to chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after cancer diagnosis and treatment. Cellular senescence, a hallmark of aging, is one of the mechanisms that contribute to accelerated aging in cancer survivors. Several aging measures, including measures based on clinical markers and biomarkers, have been proposed to estimate the aging process, and some of them have shown associations with mortality and frailty in cancer survivors. Several anti-aging interventions, including lifestyle changes and anti-aging drugs, have been proposed. Future research, particularly in large-scale studies, is needed to determine the efficiency of these aging measures and anti-aging interventions before considering their application in clinics. This review focuses on the mechanisms of cellular senescence and accelerated aging in cancer survivors, assessment of the aging process using clinical markers and biomarkers, and the high prevalence of frailty in that population, as well as possible opportunities for anti-aging interventions. A deeper understanding of aging measures and anti-aging interventions in cancer survivors will contribute to the development of effective strategies to mitigate accelerated aging in cancer survivors and improve their quality of life.
    Keywords:  accelerated aging; anti-aging interventions; cancer survivors; cellular senescence; frailty
    DOI:  https://doi.org/10.3390/ijms25063319
  8. Nature. 2024 Mar 22.
    Pregnancy advances your 'biological' age - but giving birth turns it back.
    Saima Sidik.
      
    Keywords:  Ageing; Epigenetics; Medical research
    DOI:  https://doi.org/10.1038/d41586-024-00843-w
  9. Nat Rev Nephrol. 2024 Mar 26.
    Clonal haematopoiesis and AKI.
    Susan J Allison.
      
    DOI:  https://doi.org/10.1038/s41581-024-00831-3
  10. Neural Regen Res. 2024 Nov 01. 19(11): 2333-2334
    Advancements in personalized stem cell models for aging-related neurodegenerative disorders.
    Mingxi Weng, Ralf Jauch.
      
    DOI:  https://doi.org/10.4103/NRR.NRR-D-23-01793
  11. Nat Neurosci. 2024 Mar 27.
    TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models.
    Edward N Wilson, Congcong Wang, Michelle S Swarovski, Kristy A Zera, Hannah E Ennerfelt, Qian Wang, Aisling Chaney, Esha Gauba, Javier A Ramos Benitez, Yann Le Guen, Paras S Minhas, Maharshi Panchal, Yuting J Tan, Eran Blacher, Chinyere A Iweka, Haley Cropper, Poorva Jain, Qingkun Liu, Swapnil S Mehta, Abigail J Zuckerman, Matthew Xin, Jacob Umans, Jolie Huang, Aarooran S Durairaj, Geidy E Serrano, Thomas G Beach, Michael D Greicius, Michelle L James, Marion S Buckwalter, Melanie R McReynolds, Joshua D Rabinowitz, Katrin I Andreasson.
      Human genetics implicate defective myeloid responses in the development of late-onset Alzheimer disease. A decline in peripheral and brain myeloid metabolism, triggering maladaptive immune responses, is a feature of aging. The role of TREM1, a pro-inflammatory factor, in neurodegenerative diseases is unclear. Here we show that Trem1 deficiency prevents age-dependent changes in myeloid metabolism, inflammation and hippocampal memory function in mice. Trem1 deficiency rescues age-associated declines in ribose 5-phosphate. In vitro, Trem1-deficient microglia are resistant to amyloid-β42 oligomer-induced bioenergetic changes, suggesting that amyloid-β42 oligomer stimulation disrupts homeostatic microglial metabolism and immune function via TREM1. In the 5XFAD mouse model, Trem1 haploinsufficiency prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy and changes in the disease-associated microglial transcriptomic signature. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. In postmortem Alzheimer disease brain, TREM1 colocalizes with Iba1+ cells around amyloid plaques and its expression is associated with Alzheimer disease clinical and neuropathological severity. Our results suggest that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology.
    DOI:  https://doi.org/10.1038/s41593-024-01610-w
  12. Nat Aging. 2024 Mar 22.
    Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.
    Katalin Todorov-Völgyi, Judit González-Gallego, Stephan A Müller, Nathalie Beaufort, Rainer Malik, Martina Schifferer, Mihail Ivilinov Todorov, Dennis Crusius, Sophie Robinson, Andree Schmidt, Jakob Körbelin, Florence Bareyre, Ali Ertürk, Christian Haass, Mikael Simons, Dominik Paquet, Stefan F Lichtenthaler, Martin Dichgans.
      Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
    DOI:  https://doi.org/10.1038/s43587-024-00598-z
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