bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022‒03‒20
sixteen papers selected by
Ayesh Seneviratne
University of Toronto
  1. Editorial: Dietary Strategies for Healthy Aging-Caloric Restriction and Beyond.
  2. Organelle dysfunction upon asrij depletion causes aging-like changes in mouse hematopoietic stem cells.
  3. Optimizing translational research for exceptional health and life span: A systematic narrative of studies to identify translatable therapeutic target(s) for exceptional health span in humans.
  4. Geriatric assessment in older adults with AML.
  5. Coronapod: how vaccine complacency is plaguing 'COVID zero' strategies.
  6. Socioeconomic vulnerability and frailty among community-dwelling older adults: cross-sectional findings from longitudinal aging study in India, 2017-18.
  7. Toward consensus on geriatric assessment in AML.
  8. B12 levels and frailty syndrome.
  9. Early Life Interventions Can Shape Aging.
  10. Multidimensional Short Tools to assess frailty: a narrative review.
  11. Association of Frailty with Perioperative Outcomes Following Hepatic Resection: A National Study.
  12. Phosphate Burden and Inflammation.
  13. Vaccines protect against infection from Omicron subvariant - but not for long.
  14. Immunological barriers to haematopoietic stem cell gene therapy.
  15. Prevalence of Frailty and Associated Factors Among Hospitalized Older Adults: A Cross-Sectional Study.
  16. Aging impact on amyloid precursor protein neuronal trafficking.
  1. Front Nutr. 2022 ;9 866928
    Editorial: Dietary Strategies for Healthy Aging-Caloric Restriction and Beyond.
    Sebastian J Hofer, Sergio Davinelli.
      
    Keywords:  aging; caloric restriction; caloric restriction mimetic; healthspan; nutrition
    DOI:  https://doi.org/10.3389/fnut.2022.866928
  2. Aging Cell. 2022 Mar 15. e13570
    Organelle dysfunction upon asrij depletion causes aging-like changes in mouse hematopoietic stem cells.
    Saloni Sinha, Alice Sinha, Prathamesh Dongre, Kajal Kamat, Maneesha S Inamdar.
      Aging of the blood system is characterized by increased hematopoietic stem cells (HSCs) and myeloid-biased differentiation leading to higher propensity for hematological malignancies. Unraveling cell-intrinsic mechanisms regulating HSC aging could aid reversal or slowing of aging. Asrij/OCIAD1 is an evolutionarily conserved regulator of hematopoiesis and governs mitochondrial, endosomal, and proteasomal function in mammalian stem cells. Asrij deletion in mice causes loss of HSC quiescence, myeloid skewing, reduced p53 and increased DNA damage, features attributed to aged HSCs. Mechanistically, Asrij controls p53 ubiquitination and degradation and AKT/STAT5 activation. Asrij localizes to endosomes and mitochondria. As decline in organelle structure and function are common hallmarks of aging, we asked whether Asrij regulates organelle function in aged HSCs. We find that chronologically aged wild-type (WT) HSCs had reduced Asrij levels. Expectedly, young asrij KO mice had reduced AcH4K16 levels; however, transcriptome analysis of KO HSCs showed a modest overlap of gene expression with aged WT HSCs. Further, analysis of organelle structure and function in asrij KO mice revealed significant changes, namely damaged mitochondria, elevated ROS; impaired endosomal trafficking seen by increased cleaved Notch1, reduced Rab5; and reduced 26S proteasome activity. Pharmacological correction of mitochondrial and proteasome activity in asrij KO mice restored HSC and myeloid cell frequencies. Furthermore, lysophosphatidic acid-induced Asrij upregulation in aged WT mice rescued mitochondrial and proteasome activity and restored HSC frequency. Our results highlight a new role for Asrij in preventing HSC aging by regulating organelle homeostasis and will help decipher organelle dynamics in HSC longevity.
    Keywords:  Asrij/OCIAD1; HSC; aging; endosome; homeostasis; mitochondria; organelle; proteasome
    DOI:  https://doi.org/10.1111/acel.13570
  3. J Gerontol A Biol Sci Med Sci. 2022 Mar 12. pii: glac065. [Epub ahead of print]
    Optimizing translational research for exceptional health and life span: A systematic narrative of studies to identify translatable therapeutic target(s) for exceptional health span in humans.
    Nalini Raghavachari, Beth Wilmot, Chhanda Dutta.
      Exceptional longevity as illustrated by the lower incidence and delayed onset of age-related disabilities/diseases that include cardiovascular disease, Alzheimer's disease (AD), cancer is believed to be influenced by inherent protective molecular factors in exceptionally long-lived individuals. Unraveling these protective factors could lead to the discovery of therapeutic target(s) and interventions to promote healthy aging. In this context, NIA has established a collection of translational longevity research projects (i.e., the Long Life Family Study, the Longevity Consortium, Longevity Genomics and the Integrative Longevity Omics) which are generating large omics data sets spanning the human genome to phenome and have embarked on cross-species multi-omic data analyses integrating human and non-human species that display wide variation in their lifespans. It is expected that these studies will discover key signaling pathways that influence exceptional health span and identify therapeutic targets for translation to enhance health and life span. Other efforts related to translational longevity research include the 'Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins study', which focuses on potential effects in humans of polypeptides/proteins whose circulating levels change with age, and for which experimental evidence indicates reversal or acceleration of aging changes. The 'Predictive Human Mechanistic Markers Network' is devoted to the development of predictive markers of aging, for target engagement when testing novel interventions for healthy aging. We describe here, the significance, the unique study design, categories of data sets analytical strategies and a data portal to facilitate open science and sharing of resources from these longevity studies to identify and validate potential therapeutic targets for healthy aging.
    DOI:  https://doi.org/10.1093/gerona/glac065
  4. Blood. 2022 Mar 17. 139(11): 1773
    Geriatric assessment in older adults with AML.
      
    DOI:  https://doi.org/10.1182/blood.2022015908
  5. Nature. 2022 Mar 18.
    Coronapod: how vaccine complacency is plaguing 'COVID zero' strategies.
    Noah Baker, Nicky Phillips.
      
    Keywords:  Public health; SARS-CoV-2; Vaccines
    DOI:  https://doi.org/10.1038/d41586-022-00828-7
  6. BMC Geriatr. 2022 Mar 14. 22(1): 201
    Socioeconomic vulnerability and frailty among community-dwelling older adults: cross-sectional findings from longitudinal aging study in India, 2017-18.
    Shobhit Srivastava, T Muhammad.
      INTRODUCTION: The Indian population is rapidly aging with huge proportion of illiterate and socioeconomically disadvantaged people and there is a dearth of research on the relationships between factors of socioeconomic vulnerability and frailty in older people. The present study examined the cross-sectional associations between socioeconomic vulnerability and physical frailty in community-dwelling older individuals in India.MATERIALS AND METHODS: The data for the study were obtained from the Longitudinal Aging Study in India (LASI), which was conducted in 2017-18. The effective sample size was 14,652 older males and 15,899 older females aged 60 and over. The outcome variable was physical frailty phenotype measured from exhaustion, unintentional weight loss, weak grip strength, low physical activity, and slow walking time. The main explanatory variable was vulnerability status based on education, wealth and caste. The study carried out bivariate analysis to observe the association between vulnerability status and physical frailty. Further, multivariable binary logistic regression analysis was conducted to fulfil the objective of the study.
    RESULTS: A proportion of 10.5 and 14.4% of older males and females respectively were in the overall vulnerable category. The prevalence of physical frailty was high among older males from vulnerable population (31.4% vs 26.9%; p < 0.001). The adjusted estimates from multivariate analysis revealed that older adults from vulnerable category had 14% significantly higher odds of being frail in comparison to non-vulnerable category [AOR: 1.14; CI: 1.06,1.24]. The adjusted model further revealed that there were no significant gender differentials in physical frailty among older adults. Model-3 (adjusted model) revealed that older males and females from vulnerable population had 18% [AOR: 1.18; CI: 1.04,1.34] and 8% [AOR: 1.08; CI: 1.01,1.21] significantly higher odds of being physically frail in comparison to older males from non-vulnerable population respectively.
    CONCLUSIONS: Adverse socioeconomic circumstances such as low education, lower wealth and caste status that are associated with increased prevalence of physical frailty raise urgent questions both for public health practitioners and clinicians. The current findings may help to adapt public policies focusing on screening physical frailty in the clinical settings, especially among vulnerable populations as a marker of a possibly reversible vulnerability to adverse outcomes in old age.
    Keywords:  Frailty; India; LASI; Older adults; Vulnerability
    DOI:  https://doi.org/10.1186/s12877-022-02891-1
  7. Blood. 2022 Mar 17. 139(11): 1605-1606
    Toward consensus on geriatric assessment in AML.
    Heidi D Klepin.
      
    DOI:  https://doi.org/10.1182/blood.2021015200
  8. J Frailty Sarcopenia Falls. 2022 Mar;7(1): 32-37
    B12 levels and frailty syndrome.
    Elisavet E Pyrgioti, Nikolaos D Karakousis.
      Vitamin B12, widely known as cobalamin, is a water-soluble vitamin crucial for human metabolism. It is synthesized only by prokaryotic organisms and since humans do not have the ability to synthesize it, they rely on its exogenous dietary intake. After its consumption, vitamin B12 undergoes a complicated procedure of absorption and assimilation and it is essential for cellular function, especially for nervous system, red blood cell production and DNA synthesis. Deficiency of vitamin B12 is considered as an important public health issue worldwide, while it is common in the elderly. Deficiency of this vitamin, as well as high levels, indicate a risk factor for morbidity with various clinical manifestations. Frailty is an age-related syndrome, which affects the elderly and is characterized by decreased function in many physiological systems, accompanied by vulnerability to stressors. A narrative non-systematic mini review of the literature was conducted and highlighted that vitamin B12 levels may have an impact on frailty and vice versa. As shown in several studies, vitamin B12 levels may be related to sarcopenia, cognitive and musculoskeletal disorders, neurological or psychiatric symptoms, which are closely linked to frailty. Furthermore, it is suggested that the extensions of frailty may affect the bioavailability of vitamin B12.
    Keywords:  Bioavailability; Cognitive disorders; Frailty syndrome; Sarcopenia; Vitamin B12
    DOI:  https://doi.org/10.22540/JFSF-07-032
  9. Front Endocrinol (Lausanne). 2022 ;13 797581
    Early Life Interventions Can Shape Aging.
    Andrzej Bartke, Liou Y Sun, Xinna Li, Richard A Miller.
      It is well documented that the environment of the developing fetus, including availability of nutrients and presence of toxins, can have major impact on adult phenotype, age-related traits and risk of chronic disease. There is also accumulating evidence that postnatal environment can impact adult characteristics related to evolutionary fitness, health, and aging. To determine whether early life hormonal interventions can alter trajectory of aging, we have examined the effects of early life growth hormone (GH) replacement therapy in Prop1df (Ames dwarf) mice which are GH deficient and remarkably long lived. Twice-daily GH injections between the ages of two and eight weeks completely normalized ("rescued") a number of adult metabolic characteristics believed to contribute to extended longevity of these mutants. Importantly, longevity of Ames dwarf mice was reduced by early life GH treatment. This was associated with histone H3 modifications. We conclude that the trajectory of mammalian aging can be modified by early life interventions. Mechanistic links among interventions during postnatal development, adult metabolic characteristics, aging, and longevity, apparently involve epigenetic phenomena.
    Keywords:  Developmental Origins of Health and Disease (DOHaD); aging; early life interventions; growth hormone; healthspan; lifespan; mutant mice; postnatal development
    DOI:  https://doi.org/10.3389/fendo.2022.797581
  10. Ann Ig. 2022 Mar 18.
    Multidimensional Short Tools to assess frailty: a narrative review.
    V Formosa, G Lorusso, G Lentini, E Terracciano, S Gentili, G Liotta.
      Background: The population of the European Union is progressively ageing, therefore frailty is becoming a crucial public health issue. In recent years there is a growing interest in a multidimensional concept of frailty, that is not only physical but also psychological and social, in line with a person-centered care.Study design: To measure frailty represents a fundamental step to evaluate the needs for care at both population and individual levels. Of course, to assess frailty in a large population is essential to find short and quick tools able to give reliable results in terms of risk of occurrence of negative events, to stratify older adults according to their frailty level. In this way the most appropriate strategies can be chosen and applied, to delay the functional decline associated to frailty and its consequences, such as hospitalization, institutionalization, low quality of life, and death.
    Methods: In this review we searched on PubMed for articles about scales assessing frailty with peculiar characteristics: published for the first time in 2010, available in English, with a short length and duration of administration, composed by multidimensional domains.
    Results: Seven scales were found and analyzed: The Zulfiqar Frailty Scale (ZFS), The Pictorial Fit-Frail Scale (PFFS), The Tilburg Frailty Indicator (TFI), The SUNFRAIL Tool, The (fr)AGILE, The Risk Instrument for Screening in the Community (RISC) and The Short Functional Geriatric Evaluation (SFGE). We compared their main features as the number of questions, the time for administration, the domains used and the psychometric properties as validity and reliability, with the aim of providing a set of useful information to health professionals in their everyday work.
    Conclusions: The use of these tools provides important information to help plan community health and social care and meet individuals' needs for care, but this approach is not common for community care in the EU yet.
    Keywords:   Physical; Care; Elderly; Frailty; Health; Multidimensional evaluation; Primary care; Psychological; Short tool; Social
    DOI:  https://doi.org/10.7416/ai.2022.2516
  11. J Am Med Dir Assoc. 2022 Mar 15. pii: S1525-8610(22)00187-6. [Epub ahead of print]
    Association of Frailty with Perioperative Outcomes Following Hepatic Resection: A National Study.
    Josef Madrigal, Joseph Hadaya, Cory Lee, Zachary Tran, Peyman Benharash.
      OBJECTIVES: Risk of mortality and major comorbidity remains high following hepatic resection. Given recent advancements in nonsurgical techniques to control hepatic malignancy, accurate assessment of surgical candidates, especially those considered frail, has become imperative. The present study aimed to characterize the impact of frailty on clinical and financial outcomes following hepatic resection in older individuals.DESIGN: Retrospective cohort study.
    SETTING AND PARTICIPANTS: All older adults (≥65 years) undergoing elective hepatic resection were identified from the 2012 to 2019 National Inpatient Sample.
    METHODS: Frailty was defined by using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Multivariable regression models were developed to assess the independent association of frailty with mortality, perioperative complications, and resource utilization. Marginal effects were tabulated to assess the impact of hospital volume on frailty-associated mortality.
    RESULTS: Of an estimated 40,735 patients undergoing major hepatic resection, 9.0% were considered frail. After multivariable adjustment, frailty was associated with increased odds of mortality (adjusted odds ratio [AOR] 2.9; 95% confidence interval [CI] 2.0-4.3; P < .001) and perioperative complication (AOR 2.9; 95% CI 2.4-3.4; P < .001). Furthermore, frail patients incurred longer risk-adjusted length of stay (14.2 vs 6.7 days, P < .001) and greater hospitalization costs ($55,100 vs $29,300, P < .001). In assessing the impact of institutional expertise on perioperative outcomes, the marginal effect of frailty on mortality became less pronounced with increasing operative volume.
    CONCLUSIONS AND IMPLICATIONS: As the population of the United States continues to age, surgeons are increasingly likely to encounter candidates for major hepatic resection who are frail. The present study associated frailty with inferior clinical and financial outcomes; however, frailty-associated mortality became less pronounced at centers with high hepatic resection operative volume. Coding-based instruments, such as the Johns Hopkins Adjusted Clinical Groups, may identify patients from electronic medical records who may benefit from further geriatric assessment and targeted treatments.
    Keywords:  Frailty; elderly; hepatectomy; outcomes research; surgery
    DOI:  https://doi.org/10.1016/j.jamda.2022.02.004
  12. Adv Exp Med Biol. 2022 ;1362 7-13
    Phosphate Burden and Inflammation.
    Anna Sarah Erem, Satoko Osuka, Mohammed S Razzaque.
      Phosphate is an essential macromineral often introduced to the body through dietary intake. The mechanisms for maintaining phosphate levels are tightly controlled via hormonal interactions and excretion via the kidneys. However, western diets consist of high levels of inorganic phosphate, which can overwhelm the regulatory mechanisms in place for maintaining homeostasis. Recent studies have found that phosphate burden can lead to activation of inflammatory signaling in various parts of the body. In addition, individuals with impaired kidney function may also experience exacerbated symptoms of phosphate overload due to decreased filtration and elimination. Many disease states can arise as a result of phosphate burden and subsequent inflammatory signaling, including cardiovascular diseases, tumorigenesis, depression, and neuronal disorders. While the pathophysiological causes of these diseases have been elucidated, there remains a need to address the clinical impacts of excessive dietary phosphate intake and to clarify potential drug candidates that may help alleviate these conditions. This brief chapter looks to explain the overall connection between phosphate burden and inflammation in various diseases.
    Keywords:  Cytokines; FGF23; IL-1; Inflammation; Phosphate burden; Tumorigenesis
    DOI:  https://doi.org/10.1007/978-3-030-91623-7_2
  13. Nature. 2022 Mar 18.
    Vaccines protect against infection from Omicron subvariant - but not for long.
    Saima May Sidik.
      
    Keywords:  Epidemiology; Infection; Public health; SARS-CoV-2; Vaccines
    DOI:  https://doi.org/10.1038/d41586-022-00775-3
  14. Nat Rev Immunol. 2022 Mar 17.
    Immunological barriers to haematopoietic stem cell gene therapy.
    Carsten T Charlesworth, Ian Hsu, Adam C Wilkinson, Hiromitsu Nakauchi.
      Cell and gene therapies using haematopoietic stem cells (HSCs) epitomize the transformative potential of regenerative medicine. Recent clinical successes for gene therapies involving autologous HSC transplantation (HSCT) demonstrate the potential of genetic engineering in this stem cell type for curing disease. With recent advances in CRISPR gene-editing technologies, methodologies for the ex vivo expansion of HSCs and non-genotoxic conditioning protocols, the range of clinical indications for HSC-based gene therapies is expected to significantly expand. However, substantial immunological challenges need to be overcome. These include pre-existing immunity to gene-therapy reagents, immune responses to neoantigens introduced into HSCs by genetic engineering, and unique challenges associated with next-generation and off-the-shelf HSC products. By synthesizing these factors in this Review, we hope to encourage more research to address the immunological issues associated with current and next-generation HSC-based gene therapies to help realize the full potential of this field.
    DOI:  https://doi.org/10.1038/s41577-022-00698-0
  15. Clin Nurs Res. 2022 Mar 18. 10547738221082218
    Prevalence of Frailty and Associated Factors Among Hospitalized Older Adults: A Cross-Sectional Study.
    Xiuyan Lan, Bilan Yi, Xiaohuan Chen, Shuang Jin, Qiuhua Chen, Zijuan Wang.
      This study aimed to estimate the prevalence of frailty and associated factors among hospitalized older adults. It consisted of 184 hospitalized older adults recruited between October 2019 to January 2020. We used the FRAIL scale, Geriatric Depression Scale-15, and the Pittsburg Sleep Quality Index to collect data. Descriptive statistics, independent group t-test, Chi-square (χ2) tests, and logistic regression were applied to statistical analysis. It found that the prevalence of frailty among hospitalized older adults was 39.7%. Depression (Mild: OR = 5.312, 95% CI [2.384-11.833]; Moderate: OR = 6.630, 95% CI [2.077-21.160]) and low activities of daily living (ADL) (Slight dependence: OR = 5.667, 95% CI [1.308-24.557]; Moderate dependence: OR = 15.188, 95% CI [3.342-69.016]; Severe dependence: OR = 5.872, 95% CI [2.645-13.038]) were independent predictors of frailty. Future studies on the interventions to reduce depression, improve ADL and delay the progression of frailty are encouraged. We should focus more on ADL, emotional and psychological state of hospitalized older adults to prevent frailty.
    Keywords:  depression; frailty; hospitalized; older adults; sleep quality
    DOI:  https://doi.org/10.1177/10547738221082218
  16. Curr Opin Neurobiol. 2022 Mar 15. pii: S0959-4388(22)00016-2. [Epub ahead of print]73 102524
    Aging impact on amyloid precursor protein neuronal trafficking.
    Tatiana Burrinha, Guimas Almeida Cláudia.
      Neurons live a lifetime. Neuronal aging may increase the risk of Alzheimer's disease. How does neuronal membrane trafficking maintain synapse function during aging? In the normal aged brain, intraneuronal beta-amyloid (Aβ) accumulates without Alzheimer's disease mutations or risk variants. However, do changes with neuronal aging potentiate Aβ accumulation? We reviewed the membrane trafficking of the amyloid precursor protein in neurons and highlighted its importance in Aβ production. Importantly, we reviewed the evidence supporting the impact of aging on neuronal membrane trafficking, APP processing, and consequently Aβ production. Dissecting the molecular regulators of APP trafficking during neuronal aging is required to identify strategies to delay synaptic decline and protect from Alzheimer's disease.
    DOI:  https://doi.org/10.1016/j.conb.2022.102524
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