Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article

The Neuronal Overexpression of Gclc in Drosophila melanogaster Induces Life Extension With Longevity-Associated Transcriptomic Changes in the Thorax

Some effects of aging in animals are tissue-specific. In D. melanogaster neuronal overexpression of Gclc increases lifespan and improves certain physiological parameters associated with health benefits such as locomotor activity, circadian rhythmicity, and stress resistance. Our previous transcriptomic analyses of Drosophila heads, primarily composed of neuronal tissue, revealed significant changes in expression levels of genes involved in aging-related signaling pathways (Jak-STAT, MAPK, FOXO, Notch, mTOR, TGF-beta), translation, protein processing in endoplasmic reticulum, proteasomal degradation, glycolysis, oxidative phosphorylation, apoptosis, regulation of circadian rhythms, differentiation of neurons, synaptic plasticity, and transmission. Considering that various tissues age differently and age-related gene expression changes are tissue-specific, we investigated the effects of neuronal Gclc overexpression on gene expression levels in the imago thorax, which is primarily composed of muscles. A total of 58 genes were found to be differentially expressed between thoraces of control and Gclc overexpressing flies. The Gclc level demonstrated associations with expression of genes involved in the circadian rhythmicity, the genes in categories related to the muscle system process and the downregulation of genes involved in proteolysis. Most of the functional categories altered by Gclc overexpression related to metabolism including Drug metabolism, Metabolism of xenobiotics by cytochrome P450, Glutathione metabolism, Starch and sucrose metabolism, Citrate cycle (TCA cycle), One carbon pool by folate. Thus, the transcriptomic changes caused by neuron-specific Gclc overexpression in the thorax were less pronounced than in the head and affected pathways also differed from previous results. Although these pathways don't belong to the canonical longevity pathways, we suggest that they could participate in the delay of aging of Gclc overexpressing flies

eXplainable Artificial Intelligence (XAI) in aging clock models

eXplainable Artificial Intelligence (XAI) is a rapidly progressing field of machine learning, aiming to unravel the predictions of complex models. XAI is especially required in sensitive applications, e.g. in health care, when diagnosis, recommendations and treatment choices might rely on the decisions made by artificial intelligence systems. AI approaches have become widely used in aging research as well, in particular, in developing biological clock models and identifying biomarkers of aging and age-related diseases. However, the potential of XAI here awaits to be fully appreciated. We discuss the application of XAI for developing the "aging clocks" and present a comprehensive analysis of the literature categorized by the focus on particular physiological systems

Cavity-QED simulation of a quantum metamaterial with tunable disorder

We explore experimentally a quantum metamaterial based on a superconducting chip with 25 frequency-tunable transmon qubits coupled to a common coplanar resonator. The collective bright and dark modes are probed via the microwave response, i.e., by measuring the transmission amplitude of an external microwave signal. All qubits have individual control and readout lines. Their frequency tunability allows to change the number N of resonantly coupled qubits and also to introduce a disorder in their excitation frequencies with preassigned distributions. While increasing N, we demonstrate the expected N$^{1/2}$ scaling law for the energy gap (Rabi splitting) between bright modes around the cavity frequency. By introducing a controllable disorder and averaging the transmission amplitude over a large number of realizations, we demonstrate a decay of mesoscopic fluctuations which mimics an approach towards the thermodynamic limit. The collective bright states survive in the presence of disorder when the strength of individual qubit coupling to the cavity dominates over the disorder strength

Прогностические возможности КТ в диагностике хронических воспалительных осложнений дивертикулярной болезни ободочной кишки

Objective: to determine the diagnostic effectiveness of computed tomography (CT) in predicting the course of the disease in patients with chronic inflammatory complications of diverticular disease (DD).Material and methods. The study included 70 patients with a complicated course of colon diverticular disease in the phase of exacerbation of the chronic inflammatory process. All patients underwent CT of the abdominal cavity with intravenous contrast to assess the type and severity of inflammatory changes in the colon and surrounding tissues in the area of localization of diverticula. All patients received conservative treatment and were monitored as part of the ongoing study for 12 months from the moment of initial treatment at the Center. Surgical intervention due to the ineffectiveness of conservative therapy or the recurrence of the inflammatory process during the established follow-up period was considered as an unfavorable outcome of the disease (42/60%). The positive effect of drug therapy without signs of a return of the clinical picture of inflammation within 12 months was considered as a favorable outcome (28/40%). A statistical analysis of CT signs of inflammatory changes in various DD outcomes was performed to identify prognostic CT parameters.Results. Statistically significant differences were revealed between the severity of inflammatory changes according to CT data for different outcomes of the disease. In the favorable outcome group, the main part (23/28.82%) were patients with diverticulitis, in the unfavorable outcome group, 2/3 of patients (29/42.64%) were diagnosed with pericolic infiltrates, including abscesses/cavities, and colon fistulas. It was found that the thickness of the intestinal wall, the extent of inflammatory changes in the intestinal wall, the extent of inflammatory infiltration of pericolic fiber, the symptom of “centipede”, the accumulation of fluid in the pericolic region statistically significantly differed with different outcomes of chronic inflammatory complications of diverticular disease. Мultivariate Cox proportional hazard model revealed two main predictors of the onset of an unfavorable outcome – thickening of the intestinal wall and the presence of fluid in the pericolic region. Thickening of the intestinal wall at values equal to or greater than 0,6 cm increased the risk of an unfavorable outcome by 4.69 times, and the presence of fluid by 4.52 times.Conclusion. The use in clinical practice of the revealed CT predictors of the onset of an unfavorable outcome in chronic inflammatory complications of DB can serve as one of the factors for deciding on elective surgery in this category of patients. Цель исследования: определить диагностическую эффективность компьютерной томографии (КТ) в прогнозировании течения заболевания у больных с хроническими воспалительными осложнениями дивертикулярной болезни (ДБ).Материал и методы. В исследование включено 70 пациентов с осложненным течением ДБ ободочной кишки в фазу обострения хронического воспалительного процесса. Всем пациентам выполнена КТ брюшной полости с внутривенным контрастированием для оценки вида и тяжести воспалительных изменений ободочной кишки и окружающих тканей в области локализации дивертикулов. Все пациенты получили консервативное лечение и находились под наблюдением в рамках проводимого исследования в течении 12 мес с момента первичного обращения в Центр. Оперативное вмешательство в связи с неэффективностью консервативной терапии или рецидивом воспалительного процесса в установленный период наблюдения рассматривалось как неблагоприятный исход заболевания (42/60%). Положительный эффект лекарственной терапии без признаков возврата клинической картины воспаления в течение 12 мес рассматривался как благоприятный исход (28/40%). Проведен статистический анализ КТ-признаков воспалительных изменений при различных исходах ДБ для выявления прогностических КТ-параметров.Результаты. Выявлены статистически значимые различия между выраженностью воспалительных изменений по данным КТ при различных исходах заболевания. В группе благоприятного исхода основную часть (23/28,82%) составили пациенты с дивертикулитом,  в группе неблагоприятного исхода у 2/3 больных (29/42,64%) диагностированы паракишечные инфильтраты, в том числе с абсцессами/полостями, и свищи ободочной кишки. Установлено, что толщина кишечной стенки, протяженность воспалительных изменений кишечной стенки, протяженность воспалительной инфильтрации периколической клетчатки, симптом “сороконожки”, скопление жидкости в периколической области статистически значимо различались при разных исходах хронических воспалительных осложнений ДБ. Многофакторный Кокс-регрессионный анализ выявил два основных предиктора  наступления неблагоприятного исхода – утолщение кишечной стенки и наличие жидкости в периколической области. Утолщение кишечной стенки при значениях, равных или более 0,6 см, в 4,69 раза увеличивало риск наступления неблагоприятного исхода, а наличие жидкости в 4,52 раза.Заключение. Применение в клинической практике выявленных КТ-предикторов наступления неблагоприятного исхода при хронических воспалительных осложнениях ДБ может послужить одним из факторов для принятия решения о плановом хирургическом вмешательстве у этой категории пациентов

The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource

Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes