bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024‒08‒04
25 papers selected by
Ayesh Seneviratne, Western University
  1. Multiorgan biological age shows that no organ system is an island.
  2. CHIP: a clonal odyssey of the bone marrow niche.
  3. Blocking an inflammatory protein slows the pace of ageing.
  4. Anti-IL-11 antibody shows anti-ageing properties.
  5. The Longevity Med Summit: insights on healthspan from cell to society.
  6. Phytonutrients in the promotion of healthspan: a new perspective.
  7. The Role of Assistive Technology in Enabling Older Adults to Achieve Independent Living: Past and Future.
  8. Development of an epigenetic clock resistant to changes in immune cell composition.
  9. A Science-Based Review of the World's Best-Selling Book on Aging.
  10. Heart Failure With Preserved Ejection Fraction and Frailty: From Young to Superaged Coexisting HFpEF and Frailty.
  11. Cardiometabolic implications of adipose tissue aging.
  12. Aging in chronic lung disease: Will anti-aging therapy be the key to the cure?
  13. Food is brain medicine - relevance and translation to neurology.
  14. The Dual Burden of Frailty and Heart Failure.
  15. Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms.
  16. Sarcopenic obesity and pre-sarcopenia contribute to frailty in community-dwelling Italian older people: data from the FRASNET study.
  17. Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.
  18. How neuroinflammation weakens muscles.
  19. Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases.
  20. Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.
  21. Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?
  22. GLP-1 receptor agonists and their role in managing type 2 diabetes.
  23. Systematic Review: Problems With Smell Tied to Increased Frailty Risk.
  24. Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients.
  25. Amyloid-β-induced disruption of axon-initial-segment mitochondria localization: consequences for TAU missorting in Alzheimer's disease pathology.
  1. Nat Aging. 2024 Aug 02.
    Multiorgan biological age shows that no organ system is an island.
      
    DOI:  https://doi.org/10.1038/s43587-024-00690-4
  2. J Clin Invest. 2024 Aug 01. pii: e180068. [Epub ahead of print]134(15):
    CHIP: a clonal odyssey of the bone marrow niche.
    Wolfgang E Schleicher, Bridget Hoag, Marco De Dominici, James DeGregori, Eric M Pietras.
      Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how - through their impact on the BM niche - lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.
    DOI:  https://doi.org/10.1172/JCI180068
  3. Nature. 2024 Aug;632(8023): 35-36
    Blocking an inflammatory protein slows the pace of ageing.
    Richard A Miller.
      
    Keywords:  Ageing; Immunology; Therapeutics
    DOI:  https://doi.org/10.1038/d41586-024-02300-0
  4. Nat Rev Drug Discov. 2024 Aug 01.
    Anti-IL-11 antibody shows anti-ageing properties.
    Alex Eccleston.
      
    DOI:  https://doi.org/10.1038/d41573-024-00132-1
  5. Front Aging. 2024 ;5 1417455
    The Longevity Med Summit: insights on healthspan from cell to society.
    Natalie Falshaw, Michael Sagner, Richard C Siow.
      In recent years, there has been a paradigm shift with regards to ageing, challenging its traditional perception as an inevitable and natural process. Researchers have collectively identified hallmarks of ageing, nine of which were initially proposed in 2013 and expanded in 2023 to include disabled macroautophagy, chronic inflammation, and dysbiosis, enhancing our understanding of the ageing process at microscopic, cellular, and system-wide levels. Strategies to manipulate these hallmarks present opportunities for slowing, preventing, or reversing age-related diseases, thereby promoting longevity. The interdependence of these hallmarks underscores the necessity of a comprehensive, systems-based approach to address the complex processes contributing to ageing. As a primary risk factor for various diseases, ageing diminishes healthspan, leading to extended periods of compromised health and multiple age-related conditions towards the end of life. The significant gap between healthspan and lifespan holds substantial economic and societal implications. The inaugural Longevity Med Summit (4-5 May 2023, Cascais, Portugal) provided an international forum to discuss the academic and industry landscape of healthy longevity research, preventive medicine and clinical practice to enhance healthspan.
    Keywords:  biological age; diet; geroscience; healthspan; healthy ageing; longevity; preventive medicine; public health
    DOI:  https://doi.org/10.3389/fragi.2024.1417455
  6. Front Nutr. 2024 ;11 1409339
    Phytonutrients in the promotion of healthspan: a new perspective.
    Emma F Jacquier, Amira Kassis, Diana Marcu, Nikhat Contractor, Jina Hong, Chun Hu, Marissa Kuehn, Christopher Lenderink, Arun Rajgopal.
      Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective-namely-how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.
    Keywords:  aging; healthspan; intrinsic capacity; nutrition; phytonutrients; vitality
    DOI:  https://doi.org/10.3389/fnut.2024.1409339
  7. J Med Internet Res. 2024 Jul 30. 26 e58846
    The Role of Assistive Technology in Enabling Older Adults to Achieve Independent Living: Past and Future.
    Anna Sweeting, Katie A Warncken, Martyn Patel.
      In this viewpoint, we present evidence of a marked increase in the use of assistive technology (AT) by older adults over the last 25 years. We also explain the way in which this use has expanded not only as an increase in terms of the total number of users but also by going beyond the typical scopes of use from its inception in 1999 to reach new categories of users. We outline our opinions on some of the key driving forces behind this expansion, such as population demographic changes, technological advances, and the promotion of AT as a means to enable older adults to achieve independent living. As well as our review of the evolution of AT over the past 25 years, we also discuss the future of AT research as a field and the need for harmonization of terminology in AT research. Finally, we outline how our experience in North Norfolk (notably the United Kingdom's most old age-dependent district) suggests that cocreation may be the key to not only successful research trials in the field of AT but also to the successful sustained adoption of AT beyond its original scope of use.
    Keywords:  North Norfolk; UK; aging; aging in place; assistive technology; barrier; cocreation; design; disability; independent living; injury; older adults; research trial; tool; use; users
    DOI:  https://doi.org/10.2196/58846
  8. Commun Biol. 2024 Aug 02. 7(1): 934
    Development of an epigenetic clock resistant to changes in immune cell composition.
    Alan Tomusiak, Ariel Floro, Ritesh Tiwari, Rebeccah Riley, Hiroyuki Matsui, Nicolas Andrews, Herbert G Kasler, Eric Verdin.
      Epigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age. Here, we found that human naive CD8+ T cells, which decrease in frequency during aging, exhibit an epigenetic age 15-20 years younger than effector memory CD8+ T cells from the same individual. Importantly, homogenous naive T cells isolated from individuals of different ages show a progressive increase in epigenetic age, indicating that current epigenetic clocks measure two independent variables, aging and immune cell composition. To isolate the age-associated cell intrinsic changes, we created an epigenetic clock, the IntrinClock, that did not change among 10 immune cell types tested. IntrinClock shows a robust predicted epigenetic age increase in a model of replicative senescence in vitro and age reversal during OSKM-mediated reprogramming.
    DOI:  https://doi.org/10.1038/s42003-024-06609-4
  9. Arch Gerontol Geriatr. 2023 Jan;104 104825
    A Science-Based Review of the World's Best-Selling Book on Aging.
    Charles Brenner.
      
    DOI:  https://doi.org/10.1016/j.archger.2022.104825
  10. Int J Heart Fail. 2024 Jul;6(3): 93-106
    Heart Failure With Preserved Ejection Fraction and Frailty: From Young to Superaged Coexisting HFpEF and Frailty.
    Amina Rakisheva, Anzhela Soloveva, Anastasia Shchendrygina, Ilya Giverts.
      Being commonly diagnosed in elderly women and associated with comorbidities as well as ageing-related cardio-vascular changes, heart failure with preserved ejection fraction (HFpEF) has been recently considered as a distinct cardiogeriatric syndrome. Frailty is another frequent geriatric syndrome. HFpEF and frailty share common underlying mechanisms, often co-exist, and represent each other's risk factors. A threshold of 65 years old is usually used to screen patients for both frailty and HFpEF in research and clinical settings. However, both HFpEF and frailty are very heterogenous conditions that may develop at younger ages. In this review we aim to provide a broader overview on the coexistence of HFpEF and frailty throughout the lifetime. We hypothesize that HFpEF and frailty patients' profiles (young, elderly, superaged) represent a continuum of the common ageing process modified by cumulative exposure to risk factors resulting to a presentation of HFpEF and frailty at different ages. We believe, that suggested approach might stimulate assessment of frailty in HFpEF assessment and vice versa regardless of age and early implementation of targeted interventions. Future studies of pathophysiology, clinical features, and outcomes of frailty in HFpEF by age are needed.
    Keywords:  Diagnosis; Frail elderly; Frailty; Heart failure; Middle aged; Young adult
    DOI:  https://doi.org/10.36628/ijhf.2023.0064
  11. Obes Rev. 2024 Jul 30. e13806
    Cardiometabolic implications of adipose tissue aging.
    Bulbul Ahmed, Melissa G Farb, Noyan Gokce.
      Adipose tissue is a large endocrine organ that serves numerous physiological functions. As we age, adipose tissue remodels and can develop functional changes that alters its phenotype, potentially contributing to metabolic and cardiovascular disorders. Aging adipose tissue is characterized by regional redistribution of fat, accumulation of senescent cells, fibrosis, and decline in adipocyte differentiation capacities, which collectively impact adipose tissue function and whole body health. A notable transformation involves increased accumulation of intra-abdominal visceral adipose tissue and ectopic fat around internal organs such as the heart, blood vessels, liver, and kidneys that alter their functions. Other changes associated with aging include alterations in adipokine secretion and changes in adipocyte size and numbers. Aging adipocytes play a role in mediating chronic inflammation, metabolic dysfunction, and insulin resistance. Visceral adipose tissue, which increases in volume with aging, is in particular associated with inflammation, angiogenic dysfunction, and microvascular abnormalities, and mediators released by visceral fat may have adverse consequences systemically in multiple target organs, including the cardiovascular system. Understanding mechanisms underlying adipose tissue aging and its impact on cardiovascular health are important for developing interventions and treatments to promote healthy aging and reduce cardiometabolic disease risk.
    Keywords:  adipose tissue; aging; and cardiovascular
    DOI:  https://doi.org/10.1111/obr.13806
  12. Eur J Pharmacol. 2024 Jul 25. pii: S0014-2999(24)00535-1. [Epub ahead of print]980 176846
    Aging in chronic lung disease: Will anti-aging therapy be the key to the cure?
    Weijie Wang, Kai Zhou, Leyuan Wang, Qiuyan Qin, Huijun Liu, Ling Qin, Ming Yang, Lin Yuan, Chi Liu.
      Chronic lung disease is the third leading cause of death globally, imposing huge burden of death, disability and healthcare costs. However, traditional pharmacotherapy has relatively limited effects in improving the cure rate and reducing the mortality of chronic lung disease. Thus, new treatments are urgently needed for the prevention and treatment of chronic lung disease. It is particularly noteworthy that, multiple aging-related phenotypes were involved in the occurrence and development of chronic lung disease, such as blocked proliferation, telomere attrition, mitochondrial dysfunction, epigenetic alterations, altered nutrient perception, stem cell exhaustion, chronic inflammation, etc. Consequently, senescent cells induce a series of pathological changes in the lung, such as immune dysfunction, airway remodeling, oxidative stress and regenerative dysfunction, which is a critical issue that needs special attention in chronic lung diseases. Therefore, anti-aging interventions may bring new insights into the treatment of chronic lung diseases. In this review, we elaborate the involvement of aging in chronic lung disease and further discuss the application and prospects of anti-aging therapy.
    Keywords:  Anti-Aging therapy; Chronic lung disease; Lung aging; SASP; Senescent cells
    DOI:  https://doi.org/10.1016/j.ejphar.2024.176846
  13. Nat Rev Neurol. 2024 Aug 02.
    Food is brain medicine - relevance and translation to neurology.
    Mitchell S V Elkind, Kevin G Volpp.
      
    DOI:  https://doi.org/10.1038/s41582-024-01003-4
  14. Int J Heart Fail. 2024 Jul;6(3): 107-116
    The Dual Burden of Frailty and Heart Failure.
    Cristiana Vitale, Ilaria Spoletini, Giuseppe M C Rosano.
      Frailty is highly prevalent among patients with heart failure (HF) and independently predicts adverse outcomes. However, optimal frailty definitions, assessments, and management in HF remain unclear. Frailty is common in HF, affecting up to 80% of patients depending on population characteristics. Even pre-frailty doubles mortality risk versus robust patients. Frailty worsens HF prognosis through systemic inflammation, neurohormonal changes, sarcopenia, and micronutrient deficiency. Simple screening tools like gait speed and grip strength predict outcomes but lack HF-specificity. Comprehensive geriatric assessment is ideal but not always feasible. Exercise, nutrition, poly-pharmacy management, and multidisciplinary care models can help stablize frailty components and improve patient-centred outcomes. Frailty frequently coexists with and exacerbates HF. Routine frailty screening should guide supportive interventions to optimize physical, cognitive, and psychosocial health. Further research on HF-specific frailty assessment tools and interventions is warranted to reduce this dual burden.
    Keywords:  Frailty; Heart failure; Prognosis; Rehabilitation; Therapy
    DOI:  https://doi.org/10.36628/ijhf.2023.0057
  15. J Bone Oncol. 2024 Aug;47 100620
    Senescence in the bone marrow microenvironment: A driver in development of therapy-related myeloid neoplasms.
    Angelo Jose Guilatco, Mithun Vinod Shah, Megan Moore Weivoda.
      Therapy-related myeloid neoplasms (t-MN) are a growing concern due to the continued use of cytotoxic therapies to treat malignancies. Cytotoxic therapies have been shown to drive therapy-induced senescence in normal tissues, including in the bone marrow microenvironment (BMME), which plays a crucial role in supporting normal hematopoiesis. This review examines recent work that focuses on the contribution of BMME senescence to t-MN pathogenesis, as well as offers a perspective on potential opportunities for therapeutic intervention.
    Keywords:  Bone marrow microenvironment; Bone marrow stromal cell; Clonal hematopoiesis; Myeloid neoplasm; Senescence; Senolytics
    DOI:  https://doi.org/10.1016/j.jbo.2024.100620
  16. BMC Geriatr. 2024 Jul 31. 24(1): 638
    Sarcopenic obesity and pre-sarcopenia contribute to frailty in community-dwelling Italian older people: data from the FRASNET study.
    Sarah Damanti, Lorena Citterio, Laura Zagato, Elena Brioni, Cristiano Magnaghi, Marco Simonini, Rebecca De Lorenzo, Mariapia Ruggiero, Simona Santoro, Eleonora Senini, Marco Messina, Giordano Vitali, Paolo Manunta, Angelo A Manfredi, Chiara Lanzani, Patrizia Rovere Querini.
      BACKGROUND: The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population.METHODS: Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors.
    RESULTS: One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07-0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05-0.1, p < 0.001) and pre-sarcopenia (without obesity B 0.03, 95% C.I, 0.007-0.044, p < 0.001, with obesity B 0.11, 95% C.I. 0.05-0.16, p < 0.001) were associated with frailty. Fat mass percentage predicted frailty in people aged 65-70 years whereas, muscle strength predicted general frailty in people aged 70-81 years.
    CONCLUSION: Pre-sarcopenia and SO represent potentially treatable predictors of frailty.
    Keywords:  Body composition; Frailty index; Sarcopenia; Sarcopenic obesity
    DOI:  https://doi.org/10.1186/s12877-024-05216-6
  17. Nat Commun. 2024 Jul 28. 15(1): 6357
    Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.
    James R Occean, Na Yang, Yan Sun, Marshall S Dawkins, Rachel Munk, Cedric Belair, Showkat Dar, Carlos Anerillas, Lin Wang, Changyou Shi, Christopher Dunn, Michel Bernier, Nathan L Price, Julie S Kim, Chang-Yi Cui, Jinshui Fan, Moitrayee Bhattacharyya, Supriyo De, Manolis Maragkakis, Rafael de Cabo, Simone Sidoli, Payel Sen.
      DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.
    DOI:  https://doi.org/10.1038/s41467-024-50725-y
  18. Nat Rev Immunol. 2024 Jul 29.
    How neuroinflammation weakens muscles.
    Alexandra Flemming.
      
    DOI:  https://doi.org/10.1038/s41577-024-01074-w
  19. J Intern Med. 2024 Jul 29.
    Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases.
    Xinyuan Liu, Huiwen Xue, Karin Wirdefeldt, Huan Song, Karin Smedby, Fang Fang, Qianwei Liu.
      BACKGROUND: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases.OBJECTIVE: To estimate the risk of neurodegenerative diseases among individuals with CHIP.
    METHODS: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP.
    RESULTS: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP.
    CONCLUSION: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.
    Keywords:  amyotrophic lateral sclerosis; clonal hematopoiesis of indeterminate potential; cohort study; neurodegenerative diseases
    DOI:  https://doi.org/10.1111/joim.20001
  20. Aging Cell. 2024 Jul 28. e14283
    Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.
    Dmitrii Kriukov, Ekaterina Kuzmina, Evgeniy Efimov, Dmitry V Dylov, Ekaterina E Khrameeva.
      Epigenetic aging clocks have been widely used to validate rejuvenation effects during cellular reprogramming. However, these predictions are unverifiable because the true biological age of reprogrammed cells remains unknown. We present an analytical framework to consider rejuvenation predictions from the uncertainty perspective. Our analysis reveals that the DNA methylation profiles across reprogramming are poorly represented in the aging data used to train clock models, thus introducing high epistemic uncertainty in age estimations. Moreover, predictions of different published clocks are inconsistent, with some even suggesting zero or negative rejuvenation. While not questioning the possibility of age reversal, we show that the high clock uncertainty challenges the reliability of rejuvenation effects observed during in vitro reprogramming before pluripotency and throughout embryogenesis. Conversely, our method reveals a significant age increase after in vivo reprogramming. We recommend including uncertainty estimation in future aging clock models to avoid the risk of misinterpreting the results of biological age prediction.
    Keywords:  DNA methylation; cell reprogramming; dataset shift; epigenetic aging clocks; epistemic uncertainty; rejuvenation
    DOI:  https://doi.org/10.1111/acel.14283
  21. JACC Basic Transl Sci. 2024 Jun;9(6): 827-843
    Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?
    Katrin Nitz, Joerg Herrmann, Amir Lerman, Esther Lutgens.
      The benefits of current state-of-the-art treatments to combat atherosclerotic cardiovascular disease (ASCVD) have stagnated. Treatments are mostly based on controlling cardiovascular risk factors, especially hyperlipidemia. Although the most recent advances with PCSK-9 inhibitors support the hyperlipidemia aspect of ASCVD, several lines of experimental evidence have outlined that atherosclerosis is also driven by inflammation. In the past years, phase 1, 2, and 3 clinical trials targeting inflammation to combat ASCVD have revealed that patients do tolerate such immune therapies, show decreases in inflammatory markers, and/or have reductions in cardiovascular endpoints. However, the search for the optimal anti-inflammatory or immune-modulating strategy and the stratification of patients who would benefit from such treatments and appropriate treatment regimens to combat ASCVD is only just beginning. In this review, we focus on immune checkpoint-based therapeutics (costimulation and coinhibition), many of which are already approved by the U.S. Food and Drug Administration for the treatment of cancer or autoimmune diseases, and discuss their use as a novel immunotherapeutic strategy to treat ASCVD.
    Keywords:  atherosclerosis; coinhibition; costimulation; immune system; inflammation
    DOI:  https://doi.org/10.1016/j.jacbts.2023.12.007
  22. Br J Community Nurs. 2024 Aug 02. 29(8): 391-396
    GLP-1 receptor agonists and their role in managing type 2 diabetes.
    Linda Nazarko.
      Until recently the focus in diabetes care was on managing blood glucose - a glucocentric view. This is changing to a more holistic model aimed at prevention, treatment and management through lifestyle interventions as well as medication. An estimated 5 million people in the UK are living with diabetes, most have type 2 diabetes which is associated with obesity. Type 2 diabetes can be prevented, treated with diet and weight loss, or managed with medication. The number of people with diabetes has reached epidemic proportions. To manage diabetes well and reduce complications of poorly managed diabetes, management of the condition can no longer be restricted to endocrinologists and diabetes specialist nurses. This article provides guidance on how glucagon-like peptide-1 receptor agonists can be used in the management of type 2 diabetes.
    Keywords:  GLP-1 receptor agonists (GLP-1); holistic care; management; remission; type 2 diabetes
    DOI:  https://doi.org/10.12968/bjcn.2024.0089
  23. JAMA. 2024 Aug 02.
    Systematic Review: Problems With Smell Tied to Increased Frailty Risk.
    Emily Harris.
      
    DOI:  https://doi.org/10.1001/jama.2024.13771
  24. Diabetes Metab J. 2024 Jul;48(4): 531-545
    Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients.
    Jae-Seung Yun, Kyuho Kim, Yu-Bae Ahn, Kyungdo Han, Seung-Hyun Ko.
      Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.
    Keywords:  Aged; Diabetes mellitus, type 2; Frailty; Multimorbidity; Precision medicine; Sarcopenia
    DOI:  https://doi.org/10.4093/dmj.2024.0310
  25. Neural Regen Res. 2025 May 01. 20(5): 1407-1408
    Amyloid-β-induced disruption of axon-initial-segment mitochondria localization: consequences for TAU missorting in Alzheimer's disease pathology.
    Daniel Adam, Felix Langerscheidt, Hans Zempel.
      
    DOI:  https://doi.org/10.4103/NRR.NRR-D-24-00253
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