bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024‒08‒18
nineteen papers selected by
Ayesh Seneviratne, Western University
  1. [Aging and clonal hematopoesis.]
  2. Exploring how APOE ε4 increases Alzheimer's disease risk in women.
  3. Decoding the phenotypic mosaic of aging.
  4. Decoding Clonal Hematopoiesis: Emerging Themes and Novel Mechanistic Insights.
  5. Biomarkers for aging of blood - how transferable are they between mice and humans?
  6. Real-life intrinsic capacity screening data from the ICOPE-Care program.
  7. Improving the predictive power of mouse models.
  8. Engineered Mitochondrial Transplantation as An Anti-Aging Therapy.
  9. Diagnosing sarcopenia in clinical practice: international guidelines vs. population-specific cutoff criteria.
  10. [Frailty in Oncology: Updated Recommendations for Clinical Practice].
  11. Guidelines for minimal information on cellular senescence experimentation in vivo.
  12. Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.
  13. Steatotic liver disease in the context of hematological malignancies and anti-neoplastic chemotherapy.
  14. Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.
  15. Identification of Meibomian gland stem cell populations and mechanisms of aging.
  16. Approaching the mystery of aging by the epigenetic clock.
  17. Immunosenescence: A new direction in anti-aging research.
  18. Diets.
  19. eFrailty: Making frailty assessment accessible to clinicians and researchers.
  1. Adv Gerontol. 2024 ;37(3): 266-275
    [Aging and clonal hematopoesis.]
    A N Bogdanov, S V Voloshin, E O Kunevich, M A Mikhaleva.
      The number of somatic mutations among all tissues increases along with age. This process was well-studied in hematopoietic stem cells (HSCs). Some mutations lead to a proliferative advantage and expansion of HSCs to form a dominant clone. Clonal hematopoiesis is general in the elderly population. Clonal hematopoiesis of indeterminate potential (CHIP) is a more common phenomenon in the elderly and is defined as somatic mutations in clonal blood cells without any other hematological malignancies. The development of CHIP is an independent risk factor for hematological malignancies, cardiovascular diseases, and reduced overall survival. CHIP is frequently associated with mutations in DNMT3A and TET2 genes involved in DNA methylation. The epigenetic human body clocks have been developed based on the age-related changes in methylation, making it possible to detect epigenetic aging. The combination of epigenetic aging and CHUP is associated with adverse health outcomes. Further research will reveal the significance of clonal hematopoiesis and CHIP in aging, acquiring various diseases, and determining the feasibility of influencing the mutagenic potential of clones.
    Keywords:  DNA methylation; aging; clonal hematopoiesis; epigenetic clocks; hematopoietic stem cell; somatic mutations
  2. Nat Aging. 2024 Aug 12.
    Exploring how APOE ε4 increases Alzheimer's disease risk in women.
    George Andrew S Inglis.
      
    DOI:  https://doi.org/10.1038/s43587-024-00698-w
  3. Nat Aging. 2024 Aug 09.
    Decoding the phenotypic mosaic of aging.
    Liang-Kung Chen.
      
    DOI:  https://doi.org/10.1038/s43587-024-00686-0
  4. Cancers (Basel). 2024 Jul 24. pii: 2634. [Epub ahead of print]16(15):
    Decoding Clonal Hematopoiesis: Emerging Themes and Novel Mechanistic Insights.
    Shalmali Pendse, Dirk Loeffler.
      Clonal hematopoiesis (CH), the relative expansion of mutant clones, is derived from hematopoietic stem cells (HSCs) with acquired somatic or cytogenetic alterations that improve cellular fitness. Individuals with CH have a higher risk for hematological and non-hematological diseases, such as cardiovascular disease, and have an overall higher mortality rate. Originally thought to be restricted to a small fraction of elderly people, recent advances in single-cell sequencing and bioinformatics have revealed that CH with multiple expanded mutant clones is universal in the elderly population. Just a few years ago, phylogenetic reconstruction across the human lifespan and novel sensitive sequencing techniques showed that CH can start earlier in life, decades before it was thought possible. These studies also suggest that environmental factors acting through aberrant inflammation might be a common theme promoting clonal expansion and disease progression. However, numerous aspects of this phenomenon remain to be elucidated and the precise mechanisms, context-specific drivers, and pathways of clonal expansion remain to be established. Here, we review our current understanding of the cellular mechanisms driving CH and specifically focus on how pro-inflammatory factors affect normal and mutant HSC fates to promote clonal selection.
    Keywords:  Asxl1; CHIP; Dnmt3a; Tet2; clonal evolution; clonal hematopoiesis; clonal selection; hematopoietic stem cells; inflammation; self-renewal
    DOI:  https://doi.org/10.3390/cancers16152634
  5. Exp Hematol. 2024 Aug 09. pii: S0301-472X(24)00459-4. [Epub ahead of print] 104600
    Biomarkers for aging of blood - how transferable are they between mice and humans?
    Vithurithra Tharmapalan, Wolfgang Wagner.
      Aging significantly impacts the hematopoietic system, reducing its regenerative capacity and ability to restore homeostasis after stress. Mouse models have been invaluable in studying this process due to their shorter lifespan and the ability to explore genetic, treatment, and environmental influences on aging. However, not all aspects of aging are mirrored between species. This review compares three key aging biomarkers in the hematopoietic systems of mice and humans: myeloid bias, telomere attrition, and epigenetic clocks. Myeloid bias, marked by an increased fraction of myeloid cells and decreased lymphoid cells, is a significant aging marker in mice but is scarcely observed in humans after childhood. Conversely, telomere length is a robust aging biomarker in humans, whereas mice exhibit significantly different telomere dynamics, making telomere length less reliable in the murine system. Epigenetic clocks, based on DNA methylation changes at specific genomic regions, provide precise estimates of chronological age in both mice and humans. Notably, age-associated regions in mice and humans occur at homologous genomic locations. Epigenetic clocks, depending on the epigenetic signatures used, also capture aspects of biological aging, offering powerful tools to assess genetic and environmental impacts on aging. Taken together, not all blood aging biomarkers are transferable between mice and humans. When using murine models to extrapolate human aging, it may be advantageous to focus on aging phenomena observed in both species. In conclusion, while mouse models offer significant insights, selecting appropriate biomarkers is crucial for translating findings to human aging.
    Keywords:  Aging; DNA methylation; blood; epigenetic clock; humans; mice; myeloid bias; telomere
    DOI:  https://doi.org/10.1016/j.exphem.2024.104600
  6. Nat Aging. 2024 Aug 09.
    Real-life intrinsic capacity screening data from the ICOPE-Care program.
    Philipe de Souto Barreto, Emmanuel Gonzalez-Bautista, Heike A Bischoff-Ferrari, Vitor Pelegrim de Oliveira, Renato Gorga Bandeira de Mello, Sandrine Andrieu, Caroline Berbon, Neda Tavassoli, John R Beard, Yves Rolland, Maria Eugenia Soto Martín, Bruno Vellas.
      The Integrated Care for Older People (ICOPE) program is a healthcare pathway that uses a screening test for intrinsic capacity (IC) as its entry point. However, real-life data informing on how IC domains cluster and change over time, as well as their clinical utility, are lacking. Using primary healthcare screening data from more than 20,000 French adults 60 years of age or older, this study identified four clusters of IC impairment: 'Low impairment' (most prevalent), 'Cognition+Locomotion+Hearing+Vision', 'All IC impaired' and 'Psychology+Vitality+Vision'. Compared to individuals with 'Low impairment', those in the other clusters had higher likelihood of having frailty and limitations in both activities of daily living (ADL) and instrumental activities of daily living (IADL), with the strongest associations being observed for 'All IC impaired'. This study found that ICOPE screening might be a useful tool for patient risk stratification in clinical practice, with a higher number of IC domains impaired at screening indicating a higher probability of functional decline.
    DOI:  https://doi.org/10.1038/s43587-024-00684-2
  7. Nat Biotechnol. 2024 Aug;42(8): 1175-1177
    Improving the predictive power of mouse models.
    Martin Pera, Andy Greene, Lon Cardon, Gregory W Carter, Elissa J Chesler, Gary Churchill, Vivek Kumar, Cathleen Lutz, Steven Munger, Steve Murray, Kristen O'Connell, Laura Reinholdt, Nadia A Rosenthal.
      
    DOI:  https://doi.org/10.1038/s41587-024-02349-2
  8. Aging Dis. 2024 Jul 19.
    Engineered Mitochondrial Transplantation as An Anti-Aging Therapy.
    Rui Zhao, Chen Dong, Qian Liang, Jianlin Gao, Chi Sun, Zhifeng Gu, Yujuan Zhu.
      Aging is an inevitable and complex biological process involving multi-factorial mechanisms. Mitochondrial dysfunction is a critical factor in the aging process, characterized by a decline in mitochondrial quality and activity, leading to aging and aging-related diseases. Therefore, mitochondria have become an attractive target in anti-aging therapies. Several senolytic drugs targeting mitochondria and antioxidant agents have been used in anti-aging research in the past few years. However, these strategies may cause adverse effects with long-term medication. In this extensive review, we propose "mitochondrial transplantation," which transfers healthy mitochondria from donor cells to recipient cells to replace damaged or dysfunctional mitochondria, as a new alternative strategy for treating mitochondrial dysfunction and aging-associated diseases. In this review, we introduce the contemporary landscape of mitochondrial transplantation, then discuss intensely the successful applications of mitochondrial transplantation therapy in aging diseases such as neurodegenerative diseases, cardiovascular aging, and reproductive aging, highlighting its translational potential. Finally, we summarize and prospect the challenges and opportunities mitochondrial transplantation faces in anti-aging therapy.
    DOI:  https://doi.org/10.14336/AD.2024.0231
  9. Front Med (Lausanne). 2024 ;11 1405438
    Diagnosing sarcopenia in clinical practice: international guidelines vs. population-specific cutoff criteria.
    Arben Boshnjaku, Ermira Krasniqi.
      
    Keywords:  aging; diagnostic criteria; muscle decline; older people; overdiagnosis
    DOI:  https://doi.org/10.3389/fmed.2024.1405438
  10. Dtsch Med Wochenschr. 2024 Aug;149(17): 1009-1014
    [Frailty in Oncology: Updated Recommendations for Clinical Practice].
    Valentin Goede, Ulrich Wedding.
      Frailty is a clinical condition associated with aging and resulting in increased risk of adverse outcomes upon exogenous or endogenous stressors. In oncology, cancer treatment itself can be a stressor event. In older cancer patients, frailty therefore not only enhances the probability of age-related health events such as institutionalization or falls, but also of treatment complications such as toxicity and interruption or discontinuation of therapy. As demonstrated by recent randomized-controlled trials conducted in older cancer patients receiving systemic treatment, the evaluation of frailty by geriatric assessment (GA) followed by an adjustment of the oncological therapy as well as targeted frailty interventions help to improve cancer treatment tolerability and feasibility. Based on these data, the American Society of Clinical Oncology (ASCO) updated the clinical practice guidelines for the assessment and management of vulnerabilities in older adults receiving systemic cancer therapy. The guideline recommends the use of a new GA-tool named 'practical geriatric assessment' (PGA) to foster the implementation of GA-based frailty assessment and management in routine cancer care. This article describes the background and key aspects of these recent advances.
    DOI:  https://doi.org/10.1055/a-2115-0583
  11. Cell. 2024 Aug 08. pii: S0092-8674(24)00640-8. [Epub ahead of print]187(16): 4150-4175
    Guidelines for minimal information on cellular senescence experimentation in vivo.
    Mikolaj Ogrodnik, Juan Carlos Acosta, Peter D Adams, Fabrizio d'Adda di Fagagna, Darren J Baker, Cleo L Bishop, Tamir Chandra, Manuel Collado, Jesus Gil, Vassilis Gorgoulis, Florian Gruber, Eiji Hara, Pidder Jansen-Dürr, Diana Jurk, Sundeep Khosla, James L Kirkland, Valery Krizhanovsky, Tohru Minamino, Laura J Niedernhofer, João F Passos, Nadja A R Ring, Heinz Redl, Paul D Robbins, Francis Rodier, Karin Scharffetter-Kochanek, John M Sedivy, Ewa Sikora, Kenneth Witwer, Thomas von Zglinicki, Maximina H Yun, Johannes Grillari, Marco Demaria.
      Cellular senescence is a cell fate triggered in response to stress and is characterized by stable cell-cycle arrest and a hypersecretory state. It has diverse biological roles, ranging from tissue repair to chronic disease. The development of new tools to study senescence in vivo has paved the way for uncovering its physiological and pathological roles and testing senescent cells as a therapeutic target. However, the lack of specific and broadly applicable markers makes it difficult to identify and characterize senescent cells in tissues and living organisms. To address this, we provide practical guidelines called "minimum information for cellular senescence experimentation in vivo" (MICSE). It presents an overview of senescence markers in rodent tissues, transgenic models, non-mammalian systems, human tissues, and tumors and their use in the identification and specification of senescent cells. These guidelines provide a uniform, state-of-the-art, and accessible toolset to improve our understanding of cellular senescence in vivo.
    Keywords:  aging; humans; in vivo; mouse; senescence; senotherapy
    DOI:  https://doi.org/10.1016/j.cell.2024.05.059
  12. medRxiv. 2024 Aug 07. pii: 2024.08.06.24311497. [Epub ahead of print]
    Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.
    Myvizhi Esai Selvan, Daniel I Nathan, Daniela Guisado, Giulia Collatuzzo, Sushruta Iruvanti, Paolo Boffetta, John Mascarenhas, Ronald Hoffman, Louis J Cohen, Bridget K Marcellino, Zeynep H Gümüş.
      Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD). We analyzed whole exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes. Older UC patients (age>45) harbored increased myeloid-CHIP mutations compared to younger patients (age≤45) ( p= 0.01). Lymphoid-CHIP was more prevalent in older IBD patients ( p =0.007). Young CD patients were found to have myeloid-CHIP with high-risk features. IBD patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP ( p= 0.05), while anti-TNF therapy was associated with decreased myeloid-CHIP ( p= 0.03). Pathway enrichment analyses indicated overlap between CHIP genes, IBD phenotypes, and inflammatory pathways. Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease and acceleration of their inflammatory disease.
    DOI:  https://doi.org/10.1101/2024.08.06.24311497
  13. Metabolism. 2024 Aug 12. pii: S0026-0495(24)00227-0. [Epub ahead of print] 156000
    Steatotic liver disease in the context of hematological malignancies and anti-neoplastic chemotherapy.
    Charalampos G Pontikoglou, Theodosios D Filippatos, Angelos Matheakakis, Helen A Papadaki.
      The rising prevalence of obesity-related illnesses, such as metabolic steatotic liver disease (MASLD), represents a significant global public health concern. This disease affects approximately 30 % of the adult population and is the result of metabolic abnormalities rather than alcohol consumption. Additionally, MASLD is associated with an increased risk of cardiovascular disease (CVD), chronic liver disease, and a variety of cancers, particularly gastrointestinal cancers. Clonal hematopoiesis (CH) is a biological state characterized by the expansion of a population of blood cells derived from a single mutated hematopoietic stem cell. The presence of CH in the absence of a diagnosed blood disorder or cytopenia is known as clonal hematopoiesis of indeterminate potential (CHIP), which itself increases the risk of hematological malignancies and CVD. Steatotic liver disease may also complicate the clinical course of cancer patients receiving antineoplastic agents, a condition referred to as chemotherapy induced steatohepatitis (CASH). This review will present an outline of the various aspects of MASLD, including complications. Furthermore, it will summarize the existing knowledge on the emerging association between CHIP and MASLD and present the available data on patient cases with concurrent MASLD and hematological neoplasms. Finally, it will provide a brief overview of the chemotherapeutic drugs associated with CASH, the underlying pathophysiologic mechanisms and their clinical implications.
    Keywords:  Chemotherapy induced steatohepatitis (CASH); Chronic neutrophilic leukemia; Clonal hematopoiesis of indeterminate potential (CHIP); Hematological malignancies; Leukemia; Metabolic dysfunction-associated steatohepatitis (MASH); Metabolic steatotic liver disease (MASLD); Mucosa-associated lymphoid tissue (MALT) lymphoma; Multiple myeloma
    DOI:  https://doi.org/10.1016/j.metabol.2024.156000
  14. Commun Biol. 2024 Aug 10. 7(1): 974
    Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.
    Meric Ataman, Nitish Mittal, Lionel Tintignac, Alexander Schmidt, Daniel J Ham, Asier González, Markus A Ruegg, Mihaela Zavolan.
      Calorie restriction (CR) and treatment with rapamycin (RM), an inhibitor of the mTORC1 growth-promoting signaling pathway, are known to slow aging and promote health from worms to humans. At the transcriptome and proteome levels, long-term CR and RM treatments have partially overlapping effects, while their impact on protein phosphorylation within cellular signaling pathways have not been compared. Here we measured the phosphoproteomes of soleus, tibialis anterior, triceps brachii and gastrocnemius muscles from adult (10 months) and 30-month-old (aged) mice receiving either a control, a calorie restricted or an RM containing diet from 15 months of age. We reproducibly detected and extensively analyzed a total of 6960 phosphosites, 1415 of which are not represented in standard repositories. We reveal the effect of these interventions on known mTORC1 pathway substrates, with CR displaying greater between-muscle variation than RM. Overall, CR and RM have largely consistent, but quantitatively distinct long-term effects on the phosphoproteome, mitigating age-related changes to different degrees. Our data expands the catalog of protein phosphorylation sites in the mouse, providing important information regarding their tissue-specificity, and revealing the impact of long-term nutrient-sensing pathway inhibition on mouse skeletal muscle.
    DOI:  https://doi.org/10.1038/s42003-024-06679-4
  15. bioRxiv. 2024 Aug 10. pii: 2024.08.09.607015. [Epub ahead of print]
    Identification of Meibomian gland stem cell populations and mechanisms of aging.
    Xuming Zhu, Mingang Xu, Celine Portal, Yvonne Lin, Alyssa Ferdinand, Tien Peng, Edward E Morrisey, Andrzej A Dlugosz, Joseph M Castellano, Vivian Lee, John T Seykora, Carlo Iomini, Sarah E Millar.
      Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.
    DOI:  https://doi.org/10.1101/2024.08.09.607015
  16. Primates. 2024 Aug 14.
    Approaching the mystery of aging by the epigenetic clock.
    Miho Inoue-Murayama.
      
    DOI:  https://doi.org/10.1007/s10329-024-01148-2
  17. Int Immunopharmacol. 2024 Aug 12. pii: S1567-5769(24)01421-8. [Epub ahead of print]141 112900
    Immunosenescence: A new direction in anti-aging research.
    Hanzhou Li, Shan Lin, Yuming Wang, Yuexuan Shi, Xixing Fang, Jida Wang, Huantian Cui, Yuhong Bian, Xin Qi.
      The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as 'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer's disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research.
    Keywords:  Age-related diseases; Aging; Anti-aging; Immune system; Immunosenescence
    DOI:  https://doi.org/10.1016/j.intimp.2024.112900
  18. N Engl J Med. 2024 Aug 15. pii: 10.1056/NEJMc2408735#sa2. [Epub ahead of print]391(7): 667
    Diets.
    Merle Myerson.
      
    DOI:  https://doi.org/10.1056/NEJMc2408735
  19. J Am Geriatr Soc. 2024 Aug 12.
    eFrailty: Making frailty assessment accessible to clinicians and researchers.
    Dae Hyun Kim, Megan Cheslock, Stephanie M Sison, Ariela R Orkaby, Andrea Wershof Schwartz.
      
    DOI:  https://doi.org/10.1111/jgs.19138
This page is being maintained by Thomas Krichel. It was last updated on 2024‒10‒05 at 10:39.