Old Age
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Blood ◽  
2021 ◽  
Vol 138 (Supplement 2) ◽  
pp. LBA-2-LBA-2
Margarete A Fabre ◽  
Jose Guillherme de Almeida ◽  
Edoardo Fiorillo ◽  
Emily Mitchell ◽  
Aristi Damaskou ◽  

Abstract Human cells acquire somatic mutations throughout life, some of which can drive clonal expansion. Such expansions are frequent in the hematopoietic system of healthy individuals and have been termed clonal hematopoiesis (CH). While CH predisposes to myeloid neoplasia and some non-hematological diseases, we have limited understanding of how and when CH develops, what factors govern its behavior, how it interacts with aging and how these variables relate to malignant progression. To address these questions, we adopted the experimental approach outlined in Figure 1. We began by analyzing 1,593 blood DNA samples from 385 elderly individuals, each sampled up to 5 times over ~13 years. We used deep targeted sequencing to identify and track 697 CH clones over this period. We constructed a logistic regression model and found that the great majority of clones (92.4%) expanded at a stable exponential rate during old age, enabling accurate prediction of future clonal growth (mean absolute error of measured vs predicted clone size: 3.5%). Different mutations drove substantially different growth rates, with mutations in DNMT3A and TP53 displaying the slowest average annual growth rates of ~5%. Clones with mutations in the other common driver genes (TET2, ASXL1, PPM1D and SF3B1), expanded at roughly twice this rate, i.e. ~10%/yr. The most rapidly expanding clones were those carrying SRSF2-P95H mutations, which grew at rates of over 50%/yr. Most hotspot mutations, including those at DNMT3A-R882, were not associated with faster growth than other mutations in the same gene. Growth of different clones bearing the same driver mutation varied by +/-5%/yr, proportionately impacting "slow" drivers most substantially. To investigate lifelong clonal behavior, we first used retrograde extrapolation of observed trajectories to infer the age at which each clone had begun to expand. This led to projected ages at clonal foundation that preceded conception for many clones, implying that their early growth must have been faster than the rate we observed during old age. This was most striking for DNMT3A, for which more than two thirds of projections were implausible (i.e. onset pre-conception), less common for TET2 and very uncommon for splicing factor genes. Quantification of the minimum lifetime rate at which clones must have grown in order to reach observed VAFs confirmed that deceleration was particularly marked for DNMT3A-mutant clones, whose early growth was at least twice as fast as growth during old age. To further characterize clonal dynamics over the human lifespan, we analysed hematopoietic phylogenies from 7 older individuals (aged 73-83 years), constructed using somatic mutations as lineage-tracing barcodes in 1,731 whole genome-sequenced hematopoietic colonies. We used the timing and density of clonal branching to age the onset of clonal expansions and to reconstruct their lifelong growth trajectories. In conjunction with findings from our longitudinal cohort, we revealed distinct patterns of clonal behavior. DNMT3A-mutant clones preferentially initiated and expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. In contrast, TET2 mutations were able to found clones fairly uniformly through life and drove more stable growth across ages. This disparity in behavior might explain why TET2 "overtook" DNMT3A as the most common CH driver after the age of 75 years. In diametric contrast to DNMT3A and unlike other genes, CH driven by mutant U2AF1 and SRSF2-P95H only initiated late in life and exhibited the fastest expansion dynamics. Finally, we explored the relationship between CH growth rates and malignant progression, building on our previous study of Acute Myeloid Leukemia (AML) risk prediction (Abelson et al, Nature 2018), and applying dN/dS analyses to published data (Papaemmanuil et al, Blood 2013 and NEJM 2016) to quantify selective pressures on different gene mutations in myeloid cancers. We found that mutations associated with faster CH growth were also those associated with higher risk of progression to AML (adjustedR 2=0.55, p=0.004) and were under the strongest selective pressure in AML and Myelodysplastic Syndromes (adjustedR 2=0.19, p=0.002). Collectively, our findings characterize the lifelong natural history of CH and give fundamental insights into the interactions between somatic mutation, aging and clonal selection. Figure 1 Figure 1. Disclosures Campbell: Mu Genomics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Vassiliou: Astrazeneca: Consultancy; STRM.BIO: Consultancy.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Lucy N. W. Mungai ◽  
Zanuba Mohammed ◽  
Michuki Maina ◽  
Omar Anjumanara

Vitamin D is an important hormone that is known for the regulation of calcium and phosphate metabolism. Vitamin D deficiency leads to rickets in children and osteoporosis in adults leading to poor bone mineralisation and can also lead to serious dental complications in the same population. Recent studies have shown vitamin D to work as a hormone needed not only in bone and teeth but also in other body organs from intrauterine life up to old age. It has been demonstrated that Vitamin D has various effects on biological processes that deal with cell growth, differentiation, cell death, immune regulation, DNA stability, and neuronal growth. Despite being readily formed in the body through the intervention of the sun, patients are still found to have low vitamin D levels. We review studies done to show how vitamin D works.

2021 ◽  
pp. 126-133
V. A. Golovacheva ◽  
A. A. Golovacheva

Patients with COVID-19 may develop various neurological disorders of the central and peripheral nervous systems. It is known that diabetes mellitus (DM) type 1 or 2, cardiovascular diseases, obesity, old age and old age, male gender are risk factors for a severe course and complications of COVID-19. Currently, the COVID-19 pandemic is ongoing, and patients with the listed risk factors are recommended to follow a regime of social restriction or self-isolation. Outpatient treatment is most appropriate for this category of patients. Patients with diabetes who have undergone COVID-19 are at risk of developing or progressing diabetic polyneuropathy (DPN). It seems relevant to develop the principles of effective treatment of patients with DM and DPN in outpatient settings. Glycemic level correction, diet, weight normalization, therapy of combined cardiovascular diseases, an increase of physical activity, sleep normalization, maintenance of normal psychological state are the main principles of treatment of patients with DM and DPN in COVID-19 pandemic conditions. Pathogenetic therapy of DPN continues to be discussed, in our country the preparations of B vitamins, alpha-lipoic acid are widely used. B-group vitamin preparations can be used in the form of tablets or solutions for intramuscular injections. The effectiveness of B vitamins (B1, B6, B12) in the treatment of a severe course of COVID- 19, prevention of complications of COVID-19, especially in elderly patients and with diabetes is discussed.

2021 ◽  
Vol 6 (5) ◽  
pp. 1
Nitsa Dori

Gender and ageism as mirrored in illustrations of grandmothers in Hebrew children’s books (1930-2020), shed light on the Israeli reality, which shows the world’s portrayal of grandmothers as sometimes empowering and sometimes discriminatory. This article draws from the fields of the visual arts, gender studies, sociology, and culture, and emphasizes the power of illustration in children’s literature as an activistic tool for changing social and familial awareness among young receivers. The grandmother (and, recently, also the grandfather) is a popular character in children’s literature. The article will present models which shape the consciousness of children’s book illustrators regarding old age with the aid of many visual examples. This article will enable deeper understanding of the gender-based messages and effects of visual interpretation. This study can serve as a tool for educators and parents, to help children develop critical, independent, and value-based thinking. The article concludes that in today’s books, grandmothers appear more connected to advanced technology than ever. The illustrators of today’s children’s books connect with the model of the new grandmother and draw her wearing jeans and without wrinkles. In parallel, we also see traditionally-portrayed grandmothers in certain illustrations in recent books, from a post-feminist, rather than stereotypical, approach.

Rob Rusconi

The rationale for the regulation of participants in financial markets, like retirement funds, is sound. It would be strengthened, however, by a clear statement of the objectives of such regulation. In this article the position is taken that the objectives underpinning the regulation of South African privately-managed retirement funds should be enhanced. It presents this argument with reference to international principles concerning systems of old-age provision, and to the examples of regulations in other jurisdictions. It recommends a set of practical regulatory objectives in the pursuit of efficiency, sustainability, coverage, adequacy and security of provision for old age.

2021 ◽  
Jun Gyo Gwon ◽  
Cheol Woong Jung ◽  
Chang Hun Lee ◽  
Myung-Gyu Kim

Abstract Background: Optimized postoperative fluid management is important for maintaining early allograft function after kidney transplantation (KT). However, there is still no clear guidance regarding fluid treatment after KT. In this study, we investigated the effect of perioperative fluid balance on postoperative allograft function.Methods: Recipients who underwent KT between March 2012 and August 2018 were included, and their medical records were reviewed retrospectively. We calculated fluid balance, which is the difference between total input and output during the 3 days after KT, and analyzed the change in estimated glomerular filtration rate (eGFR) according to fluid balance.Results: A total of 178 patients were included after excluding those with delayed graft function or urine output <2000 ml on the first day after KT. Among them, 116 received kidneys from living donors and 62 received kidneys from deceased donors. The total fluid balance up to day 3 was 4,236.9 ± 2830.4 ml. Old age, high body mass index (BMI), excessive positive fluid balance of the recipient, and high final creatinine of the donor were significantly associated with low eGFR at 1 week. In addition, old age, BMI, and fluid balance of the recipient predicted the 1-month eGFR. In multivariate analysis, an excessive positive fluid balance was an independent predictor of low 1-week eGFR (p=0.031). Conclusions: This study demonstrated that excessive positive fluid balance can negatively affect early graft function after KT. Proper fluid management strategies based on volume conditions may provide important therapeutic opportunities to improve early renal outcomes after KT.

2021 ◽  
Vol 7 (3) ◽  
pp. 435-452 ◽  
Alexa Ellis ◽  
María Inés Susperreguy ◽  
David J. Purpura ◽  
Pamela E. Davis-Kean

A recent meta-analysis demonstrated the overall correlation between the number line estimation (NLE) task and children’s mathematical competence was r = .44 (positively recoded), and this relation increased with age. The goal of the current study was to conceptually replicate and extend these results by further synthesizing this correlation utilizing studies not present in the meta-analysis. Across seven studies, 954 participants, ranging from 3 to 11 years old (Age M = 6.02 years, SD = 1.57), the overall estimation-competence correlations were similar to those of the meta-analysis and ranged from r = −.40 to −.35. The current conceptual replication demonstrated that the meta-analysis captured a stable overall relation between performance on the NLE task and mathematical competence. However, the current study failed to replicate the same moderation of age group presented in the meta-analysis. Furthermore, the current study extended results by assessing the stability and predictive validity of the NLE task while controlling for covariates. Results suggested that the NLE task demonstrated poor stability and predictive validity in the seven samples present in this study. Thus, although concurrent relations replicated, the differential age moderation, lack of stability, and lack of predictive validity in these studies require a more nuanced approach to understanding the utility of the NLE task. Future research should focus on understanding the connection between children’s developmental progression and NLE measurement before further investigating the predictive and diagnostic importance of the task for broader mathematical competence.

2021 ◽  
Vol 11 (12) ◽  
pp. 1258
Gil Myeong Seong ◽  
Ae-Rin Baek ◽  
Moon Seong Baek ◽  
Won-Young Kim ◽  
Jin Hyoung Kim ◽  

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (≥65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value < 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making.

2021 ◽  
Vol 25 (12) ◽  
pp. 926-927
Steven H. Yale ◽  
Halil Tekiner ◽  
Eileen S. Yale ◽  

2021 ◽  
Laura Gowing

Ingenious Trade recovers the intricate stories of the young women who came to London in the late seventeenth century to earn their own living, most often with the needle, and the mistresses who set up shops and supervised their apprenticeships. Tracking women through city archives, it reveals the extent and complexity of their contracts, training and skills, from adolescence to old age. In contrast to the informal, unstructured and marginalised aspects of women's work, this book uses legal records and guild archives to reconstruct women's negotiations with city regulations and bureaucracy. It shows single women, wives and widows establishing themselves in guilds both alongside and separate to men, in a network that extended from elites to paupers and around the country. Through an intensive and creative archival reconstruction, Laura Gowing recovers the significance of apprenticeship in the lives of girls and women, and puts women's work at the heart of the revolution in worldly goods.

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