Biological age is increased by stress and restored upon recovery.

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

Sex/gender-related differences in inflammaging.

Geroscience puts mechanisms of aging as a driver of the most common age-related diseases and dysfunctions. Under this perspective, addressing the basic mechanisms of aging will produce a better understanding than addressing each disease pathophysiology individually. Worldwide, despite greater functional impairment, life expectancy is higher in women than in men. Gender differences in the prevalence of multimorbidity lead mandatory to the understanding of the mechanisms underlying gender-related differences in multimorbidity patterns and disability-free life expectancy. Extensive literature suggested that inflammaging is at the crossroad of aging and age-related diseases. In this review, we highlight the main evidence on sex/gender differences in the mechanisms that foster inflammaging, i.e. the age-dependent triggering of innate immunity, modifications of adaptive immunity, and accrual of senescent cells, underpinning some biomarkers of inflammaging that show sex-related differences. In the framework of the "gender medicine perspective", we will also discuss how sex/gender differences in inflammaging can affect sex differences in COVID-19 severe outcomes.

Real and/or potential impacts of the Covid-19 pandemic on the mental health in older adults / Impactos reais e/ou potenciais da pandemia de Covid-19 na saúde mental de idosos / Impactos reales y/o potenciales de la pandemia de Covid-19 en la salud mental de los ancianos

A pandemia de COVID-19 e as medidas de controle para conter a disseminação do vírus, como o distanciamento social, trouxeram mudanças à rotina das pessoas, mundialmente. Esse contexto pode gerar impactos adversos para a saúde mental dos indivíduos, especialmente, àqueles em maior vulnerabilidade, os idosos. O objetivo desse estudo foi analisar na literatura os impactos reais e/ou potenciais da pandemia de COVID-19 na saúde mental de idosos. Trata-se de uma revisão integrativa de literatura com buscas realizadas na Biblioteca Virtual em Saúde, que utilizou a seguinte estratégia de busca: (Coronavírus OR "Infecções por Coronavirus" OR "Coronavirus Infections" OR COVID-19) AND (idoso OR elderly OR aged) AND ("Saúde Mental" OR "Mental Health"). Foram critérios de inclusão: artigos acessados na íntegra, sem distinção de ano e idioma, indexados até o dia 11 de novembro de 2020; e os critérios de exclusão: artigos com fuga do escopo da pesquisa, revisões de literatura, arquivos multimídia e duplicados. Foram encontrados 241 registros, e após a aplicação dos critérios de elegibilidade estabelecidos restaram 27 artigos para discussão. Dentre os impactos reais/potenciais da pandemia de COVID-19 na saúde mental dos idosos, abordados nos estudos, destaca-se a ansiedade, depressão, solidão, estresse, sensação de medo ou pânico, tristeza, suicídio/ideação suicida e insônia. Apesar disso, considera-se que há uma quantidade ainda escassa de estudos voltados especificamente para a população idosa que permitam aprofundar as discussões sobre esse tema.

The COVID-19 pandemic and control measures to contain the spread of the virus, such as social detachment, have brought changes to people's routine, worldwide. This context can generate adverse impacts on the mental health of individuals, especially those most vulnerable, the older adults. The aim of this study was to analyze in the literature the real and / or potential impacts of the COVID-19 pandemic on the mental health of the older adults. It is an integrative literature review with searches performed in the Virtual Health Library, which used the following search strategy: (Coronavírus OR "Infecções por Coronavirus" OR "Coronavirus Infections" OR COVID- 19) AND (idoso OR elderly OR aged) AND ("Saúde Mental" OR "Mental Health"). Inclusion criteria were: articles accessed in full, without distinction of year and language, indexed until November 11, 2020; and exclusion criteria: articles with escape the scope of the research, literature reviews, multimedia and duplicate files, 241 records were found, and after applying the established eligibility criteria, 27 articles remained for discussion, among the actual / potential impacts of the COVID-19 pandemic on older people, addressed in the studies, anxiety, depression, loneliness, stress, feeling of fear or panic, sadness, suicide / suicidal ideation and insomnia stand out. Despite this, there is still a small amount studies specifically aimed at the older population that allow further discussions on this topic.

La pandemia de covid-19 y las medidas de control para contener la propagación del virus, como el distanciamiento social, han supuesto cambios en la rutina de las personas en todo el mundo. Este contexto puede generar impactos adversos a la salud mental de los individuos, especialmente a los más vulnerables, los ancianos. El objetivo de este estudio fue analizar en la literatura los impactos reales y/o potenciales de la pandemia de COVID-19 en la salud mental de los ancianos. Se trata de una revisión bibliográfica integradora con búsquedas realizadas en la Biblioteca Virtual de Salud, que utilizó la siguiente estrategia de búsqueda: (Coronavirus OR "Coronavirus Infections" OR "Coronavirus Infections" OR COVID-19) AND (elderly OR aged) AND ("Mental Health" OR "Mental Health"). Los criterios de inclusión fueron: artículos accedidos en su totalidad, independientemente del año y el idioma, indexados hasta el 11 de noviembre de 2020; y los criterios de exclusión: artículos que estuvieran fuera del ámbito de la investigación, revisiones bibliográficas, archivos multimedia y duplicados. Se encontraron un total de 241 registros, y tras aplicar los criterios de elegibilidad establecidos, quedaron 27 artículos para su discusión. Entre los impactos reales/potenciales de la pandemia de COVID-19 en la salud mental de los ancianos, abordados en los estudios, destacan la ansiedad, la depresión, la soledad, el estrés, la sensación de miedo o pánico, la tristeza, la ideación suicida/suicida y el insomnio. A pesar de ello, se considera que todavía hay una escasa cantidad de estudios dirigidos específicamente a la población de edad avanzada que permitan profundizar en las discusiones sobre este tema.

The hormetic and hermetic role of IL-6.

Interleukin-6 is a pleiotropic cytokine regulating different tissues and organs in diverse and sometimes discrepant ways. The dual and sometime hermetic nature of IL-6 action has been highlighted in several contexts and can be explained by the concept of hormesis, in which beneficial or toxic effects can be induced by the same molecule depending on the intensity, persistence, and nature of the stimulation. According with hormesis, a low and/or controlled IL-6 release is associated with anti-inflammatory, antioxidant, and pro-myogenic actions, whereas increased systemic levels of IL-6 can induce pro-inflammatory, pro-oxidant and pro-fibrotic responses. However, many aspects regarding the multifaceted action of IL-6 and the complex nature of its signal transduction remains to be fully elucidated. In this review we collect mechanistic insight into the molecular networks contributing to normal or pathologic changes during advancing age and in chronic diseases. We point out the involvement of IL-6 deregulation in aging-related diseases, dissecting the hormetic action of this key mediator in different tissues, with a special focus on skeletal muscle. Since IL-6 can act as an enhancer of detrimental factor associated with both aging and pathologic conditions, such as chronic inflammation and oxidative stress, this cytokine could represent a "Gerokine", a determinant of the switch from physiologic aging to age-related diseases.

Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults.

Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals-people over the age of 90 who managed to retain much of their health and functionality-could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

Haematopoietic ageing through the lens of single-cell technologies.

Human lifespan is now longer than ever and, as a result, modern society is getting older. Despite that, the detailed mechanisms behind the ageing process and its impact on various tissues and organs remain obscure. In general, changes in DNA, RNA and protein structure throughout life impair their function. Haematopoietic ageing refers to the age-related changes affecting a haematopoietic system. Aged blood cells display different functional aberrations depending on their cell type, which might lead to the development of haematologic disorders, including leukaemias, anaemia or declining immunity. In contrast to traditional bulk assays, which are not suitable to dissect cell-to-cell variation, single-cell-level analysis provides unprecedented insight into the dynamics of age-associated changes in blood. In this Review, we summarise recent studies that dissect haematopoietic ageing at the single-cell level. We discuss what cellular changes occur during haematopoietic ageing at the genomic, transcriptomic, epigenomic and metabolomic level, and provide an overview of the benefits of investigating those changes with single-cell precision. We conclude by considering the potential clinical applications of single-cell techniques in geriatric haematology, focusing on the impact on haematopoietic stem cell transplantation in the elderly and infection studies, including recent COVID-19 research.

Immune system aging and the aging-related diseases in the COVID-19 era.

The interest in the process of aging, and specifically in how aging affects the working of our immune system, has recently enormously grown among both specialists (immunologists and gerontologists) and representatives of other disciplines of health sciences. An obvious reason for this interest is the current pandemics of COVID-19, known to affect the elderly more than younger people. In this paper current knowledge about mechanisms and complex facets of human immune system aging is presented, stemming from the knowledge about the working of various parts of the immune system, and leading to understanding of immunological mechanisms of chronic, inflammatory, aging-related diseases and of COVID-19.

Age-Dependent Reduction in Asthmatic Pathology through Reprogramming of Postviral Inflammatory Responses.

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.

Adolescent THC Treatment Does Not Potentiate the Behavioral Effects in Adulthood of Maternal Immune Activation.

Both in utero exposure to maternal immune activation and cannabis use during adolescence have been associated with increased risk for the development of schizophrenia; however, whether these exposures exert synergistic effects on brain function is not known. In the present study, mild maternal immune activation (MIA) was elicited in mice with prenatal exposure to polyinosinic-polycytidylic acid (poly(I:C)), and ∆9-tetrahydrocannabinol (THC) was provided throughout adolescence in cereal (3 mg/kg/day for 5 days). Neither THC nor MIA pretreatments altered activity in assays used to characterize hyperdopaminergic states in adulthood: amphetamine hyperlocomotion and prepulse inhibition of the acoustic startle reflex. Adolescent THC treatment elicited deficits in spatial memory and enhanced spatial reversal learning in adult female mice in the Morris water maze, while exposure to MIA elicited female-specific deficits in fear extinction learning in adulthood. There were no effects in these assays in adult males, nor were there interactions between THC and MIA in adult females. While doses of poly(I:C) and THC were sufficient to elicit behavioral effects, particularly relating to cognitive performance in females, there was no evidence that adolescent THC exposure synergized with the risk imposed by MIA to worsen behavioral outcomes in adult mice of either sex.

Skin Aging, Cellular Senescence and Natural Polyphenols.

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.

Epigenetic modifications in thymic epithelial cells: an evolutionary perspective for thymus atrophy.

BACKGROUND: The thymic microenvironment is mainly comprised of thymic epithelial cells, the cytokines, exosomes, surface molecules, and hormones from the cells, and plays a vital role in the development, differentiation, maturation and homeostasis of T lymphocytes. However, the thymus begins to degenerate as early as the second year of life and continues through aging in human beings, leading to a decreased output of naïve T cells, the limited TCR diversity and an expansion of monoclonal memory T cells in the periphery organs. These alternations will reduce the adaptive immune response to tumors and emerging infectious diseases, such as COVID-19, also it is easier to suffer from autoimmune diseases in older people. In the context of global aging, it is important to investigate and clarify the causes and mechanisms of thymus involution. MAIN BODY: Epigenetics include histone modification, DNA methylation, non-coding RNA effects, and chromatin remodeling. In this review, we discuss how senescent thymic epithelial cells determine and control age-related thymic atrophy, how this process is altered by epigenetic modification. How the thymus adipose influences the dysfunctions of the thymic epithelial cells, and the prospects of targeting thymic epithelial cells for the treatment of thymus atrophy. CONCLUSION: Epigenetic modifications are emerging as key regulators in governing the development and senescence of thymic epithelial cells. It is beneficial to re-establish effective thymopoiesis, identify the potential therapeutic strategy and rejuvenate the immune function in the elderly.

Inflammation, a common mechanism in frailty and COVID-19, and stem cells as a therapeutic approach.

As our life expectancy increases, specific medical conditions appear, and new challenges are met in terms of global health. Frailty has become a medical and scientific concept to define pathologies where inflammation, depressed immune system, cellular senescence, and molecular aging converge. But more importantly, frailty is the ultimate cause of death that limits our life span and deteriorates health in an increasing proportion of the world population. The difficulty of tackling this problem is the combination of factors that influence frailty appearance, such as stem cells exhaustion, inflammation, loss of regeneration capability, and impaired immunomodulation. To date, multiple research fields have found mechanisms participating in this health condition, but to make progress, science will need to investigate frailty with an interdisciplinary approach. This article summarizes the current efforts to understand frailty from their processes mediated by inflammation, aging, and stem cells to provide a new perspective that unifies the efforts in producing advanced therapies against medical conditions in the context of frailty. We believe this approach against frailty is particularly relevant to COVID-19, since people in a state of frailty die more frequently due to the hyperinflammatory process associated with this infection.

Role of senescence in the chronic health consequences of COVID-19.

While the full impact of COVID-19 is not yet clear, early studies have indicated that upwards of 10% of patients experience COVID-19 symptoms longer than 3 weeks, known as Long-Hauler's Syndrome or PACS (postacute sequelae of SARS-CoV-2 infection). There is little known about risk factors or predictors of susceptibility for Long-Hauler's Syndrome, but older adults are at greater risk for severe outcomes and mortality from COVID-19. The pillars of aging (including cellular senescence, telomere dysfunction, impaired proteostasis, mitochondrial dysfunction, deregulated nutrient sensing, genomic instability, progenitor cell exhaustion, altered intercellular communication, and epigenetic alterations) that contribute to age-related dysfunction and chronic diseases (the "Geroscience Hypothesis") may interfere with defenses against viral infection and consequences of these infections. Heightening of the low-grade inflammation that is associated with aging may generate an exaggerated response to an acute COVID-19 infection. Innate immune system dysfunction that leads to decreased senescent cell removal and/or increased senescent cell formation could contribute to accumulation of senescent cells with both aging and viral infections. These processes may contribute to increased risk for long-term COVID-19 sequelae in older or chronically ill patients. Hence, senolytics and other geroscience interventions that may prolong healthspan and alleviate chronic diseases and multimorbidity linked to fundamental aging processes might be an option for delaying, preventing, or alleviating Long-Hauler's Syndrome.

Health status of women affected by homelessness: A cluster of in concreto human rights violations and a time for action.

Health problems of women experiencing homelessness are driven either from the usual background characteristics of this population, or from the homeless lifestyle. Apart from poverty and unemployment, transition to homelessness is often associated with substance abuse, history of victimization, stress, poor mental health and human immunodeficiency virus (HIV). Water insecurity can undermine bodily hygiene and dental health, posing a greater risk of dehydration and opportunistic infections. Exposure to extreme environmental conditions like heat waves and natural disasters increases morbidity, accelerates aging, and reduces life expectancy. Nutrition-wise, a high prevalence of food insecurity, obesity, and micronutrient deficiencies are apparent due to low diet quality and food waste. Poor hygiene, violence, and overcrowding increase the susceptibility of these women to communicable diseases, including sexually transmitted ones and COVID-19. Furthermore, established cardiovascular disease and diabetes mellitus are often either undertreated or neglected, and their complications are more widespread than in the general population. In addition, lack of medical screening and contraception non-use induce a variety of reproductive health issues. All these health conditions are tightly related to violations of human rights in this population, including the rights to housing, water, food, reproduction, health, work, and no discrimination. Thus, the care provided to women experiencing homelessness should be optimized at a multidimensional level, spanning beyond the provision of a warm bed, to include access to clean water and sanitation, psychological support and stress-coping strategies, disease management and acute health care, food of adequate quality, opportunities for employment and support for any minor dependants.

Elementary Laboratory Assays as Biomarkers of Ageing: Support for Treatment of COVID-19?

Youth, working age and the elderly: On a timeline, chronological age (CA) and biological age (BA) may dissociate; nosological entities manifest themselves at different BAs. In determining which disease corresponds to a given age decade, statistical registries of causes of death are unreliable and this does not change with SARS CoV-2 infection. Beyond adolescence, ageing metrics involve estimations of changes in fitness, including prediction models to estimate the number of remaining years left to live. A substantial disparity in biomarker levels and health status of ageing can be observed: the difference in CA and BA in the large cohorts under consideration is glaring. Here, we focus more closely on ageing and senescence metrics in order to make information available for risk analysis non the least with COVID-19, including the most recent risk factors of ABO blood type and 3p21.31 chromosome cluster impacting on C5a and SC5b-9 plasma levels. From the multitude of routine medical laboratory assays, a potentially meaningful set of assays aimed to best reflect the stage of individual senescence; hence risk factors the observational prospective SENIORLABOR study of 1,467 healthy elderly performed since 2009 and similar approaches since 1958 can be instantiated as a network to combine a set of elementary laboratory assays quantifying senescence.