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1.
Int J Environ Res Public Health ; 19(13)2022 Jul 04.
Article in English | MEDLINE | ID: covidwho-1934071

ABSTRACT

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).


Subject(s)
Aging/physiology , Geriatric Assessment , Health Promotion/methods , Longevity , Aged , Aged, 80 and over , Aging/psychology , Educational Status , Exercise , Health Status , Holistic Health , Humans , Income , Leisure Activities , Life Style , Occupations , Risk Factors , Socioeconomic Factors , Syndrome
2.
Dis Model Mech ; 14(1)2021 01 22.
Article in English | MEDLINE | ID: covidwho-1910406

ABSTRACT

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.


Subject(s)
Aging/physiology , Hematopoietic System/physiology , Single-Cell Analysis/methods , Aging/genetics , Animals , Bone Marrow/physiology , DNA Damage , Epigenome , Glycolysis , Hematopoietic Stem Cell Transplantation , Humans , Mutation , Transcriptome
4.
Immunol Lett ; 243: 19-27, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1734546

ABSTRACT

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.


Subject(s)
Aging/physiology , Immune System/immunology , Inflammation/immunology , SARS-CoV-2/physiology , Aged , Animals , COVID-19 , Humans , Immunosenescence
5.
J Immunol ; 208(6): 1467-1482, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1690085

ABSTRACT

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.


Subject(s)
Age Factors , Aging/physiology , Asthma/immunology , COVID-19/immunology , Influenza A virus/physiology , Influenza, Human/immunology , Lung/immunology , Orthomyxoviridae Infections/immunology , Respirovirus Infections/immunology , SARS-CoV-2/physiology , Sendai virus/physiology , Th2 Cells/immunology , Animals , Asthma/epidemiology , COVID-19/epidemiology , Cytokines/metabolism , Humans , Influenza, Human/epidemiology , Mice , Mice, Inbred C57BL , United States/epidemiology
6.
Cells ; 10(12)2021 12 11.
Article in English | MEDLINE | ID: covidwho-1598389

ABSTRACT

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.


Subject(s)
Aging/physiology , Behavior, Animal/drug effects , Dronabinol/pharmacology , Prenatal Exposure Delayed Effects/immunology , Amphetamine , Animals , Conditioning, Classical , Extinction, Psychological/drug effects , Fear/drug effects , Female , Locomotion/drug effects , Male , Maze Learning/physiology , Mice, Inbred C57BL , Pregnancy , Prepulse Inhibition/drug effects , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Swimming
7.
Int J Mol Sci ; 22(23)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1542580

ABSTRACT

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.


Subject(s)
Cellular Senescence/drug effects , Cellular Senescence/physiology , Polyphenols/pharmacology , Skin Aging/drug effects , Skin Aging/physiology , Aging/physiology , COVID-19 , Fibroblasts , Humans , Keratinocytes , Melanocytes , SARS-CoV-2 , Skin/pathology , Skin Aging/pathology
8.
Clin Epigenetics ; 13(1): 210, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1533277

ABSTRACT

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.


Subject(s)
Aging/physiology , Epigenesis, Genetic/physiology , Epithelial Cells/pathology , Thymus Gland/pathology , Atrophy , Humans
9.
Stem Cells Transl Med ; 10(11): 1482-1490, 2021 11.
Article in English | MEDLINE | ID: covidwho-1490914

ABSTRACT

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.


Subject(s)
COVID-19 , Frailty , Inflammation/complications , Mesenchymal Stem Cell Transplantation , Aging/physiology , COVID-19/complications , COVID-19/therapy , Frailty/etiology , Frailty/therapy , Humans , Immunomodulation/physiology , Inflammation/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/physiology , Regeneration/physiology , SARS-CoV-2 , Signal Transduction/physiology
10.
Transl Res ; 241: 96-108, 2022 03.
Article in English | MEDLINE | ID: covidwho-1475098

ABSTRACT

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.


Subject(s)
Aging/physiology , COVID-19/physiopathology , Aged , COVID-19/virology , Chronic Disease , Humans , SARS-CoV-2/isolation & purification
11.
J Am Geriatr Soc ; 69(6): 1695-1697, 2021 06.
Article in English | MEDLINE | ID: covidwho-1455580
12.
Maturitas ; 154: 31-45, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415643

ABSTRACT

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.


Subject(s)
Aging , COVID-19 , Food Insecurity , Health Status , Homeless Persons/psychology , Human Rights , Mental Health/statistics & numerical data , Substance-Related Disorders/complications , Aging/physiology , Aging/psychology , Female , Food , Humans , Reproductive Health , SARS-CoV-2 , Stress, Psychological , Substance-Related Disorders/psychology , Water Supply
16.
Gerontology ; 67(5): 503-516, 2021.
Article in English | MEDLINE | ID: covidwho-1337456

ABSTRACT

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.


Subject(s)
Aging/physiology , COVID-19/therapy , Biomarkers/metabolism , COVID-19/diagnosis , COVID-19/mortality , Humans
17.
Int J Mol Med ; 48(2)2021 Aug.
Article in English | MEDLINE | ID: covidwho-1304768

ABSTRACT

Aging causes skeletal muscle atrophy, and myofiber loss can be a critical component of this process. In 1989, Rosenberg emphasized the importance of the loss of skeletal muscle mass that occurs with aging and coined the term 'sarcopenia'. Since then, sarcopenia has attracted considerable attention due to the aging population in developed countries. The presence of sarcopenia is closely related to staggering, falls and even frailty in the elderly, which in turn leads to the need for nursing care. Sarcopenia is often associated with a poor prognosis in the elderly. Therefore, it is crucial to investigate the causes and pathogenesis of sarcopenia, and to develop and introduce interventional strategies in line with these causes and pathogenesis. Sarcopenia can be a primary component of physical frailty. The association between sarcopenia, frailty and locomotive syndrome is complex; however, sarcopenia is a muscle­specific concept that is relatively easy to approach in research. In the elderly, a lack of exercise, malnutrition and hormonal changes lead to neuromuscular junction insufficiency, impaired capillary blood flow, reduced repair and regeneration capacity due to a decrease in the number of muscle satellite cells, the infiltration of inflammatory cells and oxidative stress, resulting in muscle protein degradation exceeding synthesis. In addition, mitochondrial dysfunction causes metabolic abnormalities, such as insulin resistance, which may lead to quantitative and qualitative abnormalities in skeletal muscle, resulting in sarcopenia. The present review article focuses on age­related primary sarcopenia and outlines its pathogenesis and mechanisms.


Subject(s)
Aging/metabolism , Cytokines/metabolism , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Sarcopenia/metabolism , Aged , Aging/physiology , Humans , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Atrophy/physiopathology , Myofibrils/metabolism , Sarcopenia/pathology , Sarcopenia/physiopathology , Satellite Cells, Skeletal Muscle/metabolism
19.
Asia Pac Psychiatry ; 13(3): e12473, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1268103

ABSTRACT

BACKGROUND: Suicide among older adults is a multifactorial problem with several interrelated factors involved that vary with age, gender and culture. The number of suicides is highest in those aged 70 years or older in almost all regions of the world. With the increase in life expectancy, and the decrease in mortality due to other causes of death, we could expect the absolute number of older adults' suicide continue increasing. METHODS: Review of the literature on suicide protective factors of suicide among older adults. RESULTS: Improvements on social determinants of health and the timely detection and early treatment of affective disorders are key interventions. Prevention based on community actions and training of gatekeepers may have positive impact. Community programs that promote a sense of usefulness, belonging and that contribute to preserve social integration should be encouraged. Governments should develop the improvement of retirement programs and the development of support systems. The access to general health and mental health services should be facilitated and Primary Care professionals should receive proper training to detect and manage older persons at risk. Actively promoting a culture of coping to different stages of life and to the changes imposed by the advancing of age should form the essential part of a process bringing to better successful aging avenues. CONCLUSIONS: Suicide prevention in older adults should broaden its focus and pay attention to the many socio-environmental conditions that may be relevant in older age, especially social isolation, financial security and physical health.


Subject(s)
Aging , COVID-19/psychology , Preventive Health Services , Aged , Aging/physiology , Aging/psychology , Health Status Disparities , Humans , SARS-CoV-2 , Social Determinants of Health , Social Isolation/psychology , Suicide/prevention & control , Suicide/psychology , Suicide/statistics & numerical data
20.
Clin Interv Aging ; 16: 1037-1046, 2021.
Article in English | MEDLINE | ID: covidwho-1266601

ABSTRACT

BACKGROUND: Remdesivir, an antiviral agent able to reduce inflammatory cascade accompanying severe, life-threatening pneumonia, became the first drug approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus 2 related severe acute respiratory syndrome (SARS CoV2). As from its previously known clinical indications, the use of remdesivir in the presence of severe renal impairment is contraindicated; however, the impact of remdesivir on renal function in aging patients has not been elucidated. SUBJECTS AND METHODS: This retrospective observational study involved 109 individuals consecutively admitted in internal medicine section, Azienda Ospedaliero Universitaria Pisana hospital, in November-December 2020 due to a confirmed diagnosis of SARS CoV2 and receiving remdesivir according to international inclusion criteria. Biochemical variables at admission were evaluated, together with slopes of estimated glomerular filtration rate (eGFR) built during remdesivir treatment. Participants were followed until discharge or exitus. RESULTS: Patients were stratified according to age (80 formed the study cohort and 29 served as controls); CKD stage III was present in 46% of them. No patients showed any sign of deteriorated renal function during remdesivir. Fourteen patients in the elderly cohort deceased; their eGFR at baseline was significantly lower. Recovered patients were characterized by a relevant eGFR gaining during remdesivir treatment. CONCLUSION: We show here for the first time as remdesivir does not influence eGFR in a cohort of elderly people hospitalized for SARS CoV2, and that eGFR gain during such treatment is coupled with a better prognosis.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Aging/physiology , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Aged, 80 and over , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , COVID-19/mortality , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
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