bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022–07–24
nine papers selected by
Ayesh Seneviratne, Western University
  1. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.
  2. Novel Germline Loci Are Associated with Clonal Hematopoiesis Risk.
  3. Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.
  4. Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.
  5. The Impact of Frailty on Adverse Outcomes in Geriatric Hip Fracture Patients: A Systematic Review and Meta-Analysis.
  6. SIRT6 in Vascular Diseases, from Bench to Bedside.
  7. Calorie Restriction with or without Time-Restricted Eating in Weight Loss.
  8. Calorie Restriction with or without Time-Restricted Eating in Weight Loss. Reply.
  9. Ageing and rejuvenation of tissue stem cells and their niches.
  1. Cell Stem Cell. 2022 Jul 12. pii: S1934-5909(22)00261-2. [Epub ahead of print]
    Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.
    Ruzhica Bogeska, Ana-Matea Mikecin, Paul Kaschutnig, Malak Fawaz, Marleen Büchler-Schäff, Duy Le, Miguel Ganuza, Angelika Vollmer, Stella V Paffenholz, Noboru Asada, Esther Rodriguez-Correa, Felix Frauhammer, Florian Buettner, Melanie Ball, Julia Knoch, Sina Stäble, Dagmar Walter, Amelie Petri, Martha J Carreño-Gonzalez, Vinona Wagner, Benedikt Brors, Simon Haas, Daniel B Lipka, Marieke A G Essers, Vivienn Weru, Tim Holland-Letz, Jan-Philipp Mallm, Karsten Rippe, Stephan Krämer, Matthias Schlesner, Shannon McKinney Freeman, Maria Carolina Florian, Katherine Y King, Paul S Frenette, Michael A Rieger, Michael D Milsom.
      Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functional HSCs following challenge with inflammation or bacterial infection, with no evidence of any recovery up to 1 year afterward. HSCs from challenged mice demonstrated multiple cellular and molecular features of accelerated aging and developed clinically relevant blood and bone marrow phenotypes not normally observed in aged laboratory mice but commonly seen in elderly humans. In vivo HSC self-renewal divisions were absent or extremely rare during both challenge and recovery periods. The progressive, irreversible attrition of HSC function demonstrates that temporally discrete inflammatory events elicit a cumulative inhibitory effect on HSCs. This work positions early/mid-life inflammation as a mediator of lifelong defects in tissue maintenance and regeneration.
    Keywords:  HSCs; accelerated aging; aging; clonal hematopoiesis; hematopoietic stem cells; inflammaging; inflammation; self-renewal; stem cell exhaustion; stress hematopoiesis
    DOI:  https://doi.org/10.1016/j.stem.2022.06.012
  2. Cancer Discov. 2022 Jul 22. OF1
    Novel Germline Loci Are Associated with Clonal Hematopoiesis Risk.
      Novel germline loci were associated with the risk of clonal hematopoiesis (CH) within the UK Biobank.
    DOI:  https://doi.org/10.1158/2159-8290.CD-RW2022-132
  3. Aging Dis. 2022 Jul 11. 13(4): 970-986
    Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.
    Fang-Fang Cheng, Yan-Li Liu, Jang Du, Jun-Tang Lin.
      Aging is a major global challenge, and there is growing demand for new strategies to address the burden of aging. The intensive search for antiaging agents has led to the discovery of a variety of drugs that promote the extension of healthspan and/or life. Metformin is a safe, effective, and globally affordable antihyperglycemic agent that has gained much attention in recent years as a potential antiaging treatment. Metformin has been shown to significantly delay the onset of age-related diseases and increase lifespan in several model organisms. In this paper, we reviewed aging hallmarks and the role of metformin in countering these hallmarks. We examined the beneficial effects of metformin on several age-related diseases and the feasibility of metformin as an agent to extend lifespan and healthspan. Finally, we discussed new research directions to better understand the translational potential of metformin in humans.
    Keywords:  age-related diseases; aging hallmarks; antiaging; healthspan; metformin
    DOI:  https://doi.org/10.14336/AD.2021.1213
  4. Clin Geriatr Med. 2022 Aug;pii: S0749-0690(22)00022-2. [Epub ahead of print]38(3): 565-591
    Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.
    Gemelli Against COVID-19 Post-Acute Care Team
      The persistence of COVID-19 symptoms weeks or months after an initial SARS-CoV-2 infection has become one of the most burdensome legacies of the pandemic. This condition, known as long COVID syndrome, affects many persons of all age groups and is associated with substantial reductions of quality of life. Several mechanisms may be involved in long COVID syndrome, including chronic inflammation, metabolic perturbations, endothelial dysfunction, and gut dysbiosis. These pathogenic mechanisms overlap with those of the aging process and may aggravate pre-existing degenerative conditions. This review discusses bioactive foods, supplements, and nutraceuticals as possible interventions against long COVID syndrome.
    Keywords:  Bioactive foods; Fatigue; Frailty; Geriatrics; Gerontology; Nutrition; Sarcopenia; Therapy
    DOI:  https://doi.org/10.1016/j.cger.2022.04.004
  5. Front Public Health. 2022 ;10 890652
    The Impact of Frailty on Adverse Outcomes in Geriatric Hip Fracture Patients: A Systematic Review and Meta-Analysis.
    Yanhong Song, Ziyi Wu, Huihui Huo, Ping Zhao.
       Objective: With an aging population and advances in medicine, more research focuses on health and longevity in geriatric adults. Recently, frailty has gradually emerged to assess physical conditions. Frailty can be generally described as a multi-dimensional situation of increased vulnerabilities to both endogenous and exogenous stressors. The objective of the review was to evaluate the predictive value of frailty on adverse outcomes in geriatric hip fracture patients.
    Materials and Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant literature about the connection between frailty and poor outcomes in hip fracture elders.
    Results: Eleven studies involving a total of 45,979 participants were selected in our study. Our results indicated that frailty could significantly predict postoperative and in-patient complications (OR, 1.46; 95% CI, 1.13-1.90; I 2 = 77.4%). Frail elders had higher risk of inpatient mortality (OR, 1.68; 95% CI, 1.26-2.25; I 2 = 0.0%), 6-month mortality (OR, 1.46; 95% CI, 1.25-1.72; I 2 = 0.0%) and ≥1-year mortality (OR, 2.24; 95% CI, 1.66-3.04; I 2 = 91.3%). Furthermore, the risk of prolonged hospital stays was 1.15 times more likely in frail patients (95% CI, 1.03-1.28; I 2 = 14.8%).
    Conclusion: Frailty can predict adverse outcomes effectively in geriatric hip fracture patients.
    Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
    Keywords:  adverse outcomes; elders; frailty; hip fracture; meta-analysis
    DOI:  https://doi.org/10.3389/fpubh.2022.890652
  6. Aging Dis. 2022 Jul 11. 13(4): 1015-1029
    SIRT6 in Vascular Diseases, from Bench to Bedside.
    Si-Chong Ren, Xiangqi Chen, Hui Gong, Han Wang, Chuan Wu, Pei-Heng Li, Xiao-Feng Chen, Jia-Hua Qu, Xiaoqiang Tang.
      Aging is a key risk factor for angiogenic dysfunction and cardiovascular diseases, including heart failure, hypertension, atherosclerosis, diabetes, and stroke. Members of the NAD+-dependent class III histone deacetylase family, sirtuins, are conserved regulators of aging and cardiovascular and cerebrovascular diseases. The sirtuin SIRT6 is predominantly located in the nucleus and shows deacetylase activity for acetylated histone 3 lysine 56 and lysine 9 as well as for some non-histone proteins. Over the past decade, experimental analyses in rodents and non-human primates have demonstrated the critical role of SIRT6 in extending lifespan. Recent studies highlighted the pleiotropic protective actions of SIRT6 in angiogenesis and cardiovascular diseases, including atherosclerosis, hypertension, heart failure, and stroke. Mechanistically, SIRT6 participates in vascular diseases via epigenetic regulation of endothelial cells, vascular smooth muscle cells, and immune cells. Importantly, SIRT6 activators (e.g., MDL-800/MDL-811) have provided therapeutic value for treating age-related vascular disorders. Here, we summarized the roles of sirtuins in cardiovascular diseases; reviewed recent advances in the understanding of SIRT6 in vascular biology, cardiovascular aging, and diseases; highlighted its therapeutic potential; and discussed future perspectives.
    Keywords:  activator; aging; angiogenesis; sirt6; sirtuin; vascular disease
    DOI:  https://doi.org/10.14336/AD.2021.1204
  7. N Engl J Med. 2022 07 21. pii: 10.1056/NEJMc2207023#sa1. [Epub ahead of print]387(3): 280-281
    Calorie Restriction with or without Time-Restricted Eating in Weight Loss.
    Pedro L Valenzuela, Adrián Castillo-García, Alejandro Lucia.
      
    DOI:  https://doi.org/10.1056/NEJMc2207023
  8. N Engl J Med. 2022 07 21. pii: 10.1056/NEJMc2207023#sa2. [Epub ahead of print]387(3): 281
    Calorie Restriction with or without Time-Restricted Eating in Weight Loss. Reply.
    Deying Liu, Huijie Zhang.
      
    DOI:  https://doi.org/10.1056/NEJMc2207023
  9. Nat Rev Mol Cell Biol. 2022 Jul 20.
    Ageing and rejuvenation of tissue stem cells and their niches.
    Anne Brunet, Margaret A Goodell, Thomas A Rando.
      Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular mechanisms underlying ageing in the regenerative regions of different tissues as well as potential rejuvenation strategies. We focus primarily on brain, muscle and blood tissues, but also provide examples from other tissues, such as skin and intestine. We describe the complex interactions between different cell types, non-cell-autonomous mechanisms between ageing niches and stem cells, and the influence of systemic factors. We also compare different interventions for the rejuvenation of old regenerative regions. Future outlooks in the field of stem cell ageing are discussed, including strategies to counter ageing and age-dependent disease.
    DOI:  https://doi.org/10.1038/s41580-022-00510-w
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