Centenarians as a model for healthy aging

2003 ◽  
Vol 31 (2) ◽  
pp. 457-461 ◽  
Author(s):  
C. Franceschi ◽  
M. Bonafè
Keyword(s):  
T Cells ◽  
Stress Responses ◽  
Healthy Aging ◽  
The Body ◽  
Continuous Exposure ◽  
Chronic Infections ◽  
Inflammatory Status ◽  
Age Related ◽  
Inflammatory Drugs ◽  
Antigenic Load

For over 10 years we have studied centenarians as a model to address the biological basis of aging and longevity, with particular attention to immunology and genetics. The most important findings can be summarized as follows. (i) Human immunosenescence represents a complex remodelling, whereby clonotypical immunity deteriorates, while ancestral, innate immunity is largely preserved. (ii) Continuous exposure to antigens causes a lifelong, chronic antigenic stress, which is responsible, together with the involution of the thymus, for the accumulation of memory/effector T cells and the exhaustion of naïve T cells. (iii) Aging is characterized by a peculiar chronic inflammatory status that we propose to call ‘inflammaging’, which appears to be under genetic control, is detrimental for longevity and is more evident in men than in women. Inflammaging, i.e. the up-regulation of a variety of anti-stress responses at the cellular and molecular level, is the consequence of the ability of the body to adapt to and counteract the effects of a variety of stressors, which causes the accumulation of molecular and cellular scars. Inflammaging is considered the common and most important driving force of age-related pathologies, such as neurodegeneration, atherosclerosis, diabetes and sarcopenia, among others, all of which share an inflammatory pathogenesis. (iv) Possible strategies to counteract the major effects of immunosenescence and inflammaging, such as the systematic reduction of the lifelong antigenic load, the elimination of chronic infections, thymic rejuvenation and preventative treatment with anti-inflammatory drugs in people with a pro-inflammatory genotype, are envisaged.

scholarly journals Regular Practice of Moderate Physical Activity by Older Adults Ameliorates Their Anti-Inflammatory Status

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1780 ◽  
Author(s):  
Miguel Ferrer ◽  
Xavier Capó ◽  
Miquel Martorell ◽  
Carla Busquets-Cortés ◽  
Cristina Bouzas ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Body Composition ◽  
Healthy Aging ◽  
The Body ◽  
Moderate Physical Activity ◽  
Metabolic Equivalents ◽  
Inflammatory Status ◽  
Anti Inflammatory ◽  
Regular Practice

A chronic inflammatory state is a major characteristic of the aging process, and physical activity is proposed as a key component for healthy aging. Our aim was to evaluate the body composition, hypertension, lipid profile, and inflammatory status of older adults, and these factors’ association with physical activity. A total of 116 elderly volunteers were categorized into terciles of quantitative metabolic equivalents of task (MET). Subjects in the first and third terciles were defined as sedentary and active subjects, respectively. Anthropometric and biochemical parameters, hemograms, and inflammatory markers were measured in plasma or peripheral mononuclear blood cells (PBMCs). The active groups exercised more than their sedentary counterparts. The practice of physical activity was accompanied by lower weight, fat mass, body mass index, and diastolic blood pressure when compared to a more sedentary life-style. Physical activity also lowered the haematocrit and total leukocyte, neutrophil, and lymphocyte counts. The practice of exercise induced a decrease in the IL-6 circulating levels and the TLR2 protein levels in PBMCs, while the expression of the anti-inflammatory IL-10 was activated in active subjects. The regular practice of physical activity exerts beneficial effects on body composition and the anti-inflammatory status of old people.

scholarly journals Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice

2021 ◽  
Vol 14 (10) ◽  
pp. 1040
Author(s):  
Dolors Puigoriol-Illamola ◽  
Júlia Companys-Alemany ◽  
Kris McGuire ◽  
Natalie Z. M. Homer ◽  
Rosana Leiva ◽  
...  
Keyword(s):  
Stress Responses ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Cognitive Improvement ◽  
Age Related ◽  
Mtorc1 Signaling ◽  
Cognitive Disturbances ◽  
Samp8 Mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

scholarly journals Age-related differences in decision-making process in the context of healthy aging

2020 ◽  
Vol 22 ◽  
pp. 01022
Author(s):  
Felix Zakirov ◽  
Arsenty Krasilnikov
Keyword(s):  
Decision Making ◽  
Social Interactions ◽  
Cognitive Processes ◽  
Healthy Aging ◽  
Risky Behavior ◽  
Life Experience ◽  
The Body ◽  
Age Related ◽  
Rational Choices ◽  
Neuroimaging Data

During aging cognitive functions change differently from others. Unlike most of the body systems, there is no clear decline pattern in cognitive processes. One of the most significant cognitive processes is decision-making, which defines social interactions, economical relationships, and risky behavior. Among factors influence decisionmaking process, individual lifelong experience is considered to be an important one. Obviously, older adults have more life experience, than the younger groups. However, the former often do not tend to rational choices and beneficial strategies. In this case it is important to assess how aging processes in brain contribute into searching for the most beneficial option during decision-making. On the basis of today’s studies about risky behavior, judgement of fairness, financial games, and modern neuroimaging data this review will observe and discuss age-related differences in decision-making. Thus, a correct cognitive profile of older adult in decision-making context can be determined.

scholarly journals Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians

2019 ◽  
Author(s):  
Kosuke Hashimoto ◽  
Tsukasa Kouno ◽  
Tomokatsu Ikawa ◽  
Norihito Hayatsu ◽  
Yurina Miyajima ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Single Cell ◽  
Cd4 T Cells ◽  
Healthy Aging ◽  
Mononuclear Cells ◽  
Substantial Reduction ◽  
Clonal Expansion ◽  
Age Related

AbstractSupercentenarians, people who have reached 110 years of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from seven supercentenarians and five younger controls. We identified a marked increase of cytotoxic CD4 T-cells (CD4 CTLs) coupled with a substantial reduction of B-cells as a novel signature of supercentenarians. Furthermore, single-cell T-cell receptor sequencing of two supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15% to 35% of the entire CD4 T-cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.SignificanceExceptionally long-lived people such as supercentenarians tend to spend their entire lives in good health, implying that their immune system remains active to protect against infections and tumors. However, their immunological condition has been largely unexplored. We profiled thousands of circulating immune cells from supercentenarians at single-cell resolution, and identified a large number of CD4 T-cells that have cytotoxic features. This characteristic is very unique to supercentenarians, because generally CD4 T-cells have helper, but not cytotoxic, functions under physiological conditions. We further profiled their T-cell receptors, and revealed that the cytotoxic CD4 T-cells were accumulated through clonal expansion. The conversion of helper CD4 T-cells to a cytotoxic variety might be an adaptation to the late stage of aging.

scholarly journals TRAJECTORY OF AGE-ASSOCIATED CHANGES IN THE MICROBIAL COMMUNITY OF THE SMALL INTESTINE OF HEALTHY PERSONS IN THE CONTEXT OF METAORGANISM

2021 ◽  
Author(s):  
Yu. Filippova ◽  
M. Kholodilina ◽  
A. Burmistrova
Keyword(s):  
Small Intestine ◽  
Microbial Community ◽  
Bacterial Community ◽  
Healthy Aging ◽  
Optimal Scaling ◽  
The Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Healthy Individuals ◽  
Age Related ◽  
Neuroendocrine Systems

The study of the small intestine microbiota in humans is difficult due to the low availability of biomaterial. Non-invasive methods of metabolomics and bioinformatic data analysis can expand our understanding of the structure and role the small intestine microbiota in maintaining homeostasis of the body. The article presents the trajectory of age-related changes in the microbial community of the small intestine in healthy individuals in the context of interaction with the cytokine and neuroendocrine systems within the metaorganism, using the methods of gas chromatography - mass spectrometry of microbial markers (GCMS MM) and optimal scaling. 110 practically healthy individuals: children, adults and elderly, were included into the study. The number of the main types of small intestine microbiota (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria) was determined in peripheral blood by the GCMS MM method. To construct the trajectories of changes in the small intestine microbiota and indicators of the cytokine and neuroendocrine systems with age, the optimal scaling technique based on the multivariate Gifi transformation (CATPCA method) was used. It was found, that the bacterial community of the small intestine of both children and the elderly and seniors has a significantly low total number of microorganisms, due to the low content of bacteria of the types Firmicutes and Actinobacteria against the background of a high number of representatives of the types Proteobacteria and Fusobacteria, in comparison with similar indicators in adults. Assessment of the trajectory of age-associated changes in the microbiota of the small intestine showed: 1) children have strong dynamic fluctuations in the number and connections within the community of microorganisms against the background of the formation of connections between the main regulatory systems of the metaorganism – immune and neuroendocrine; 2) adults present the plasticity and consistency of the functioning of the immune and nervous systems, what determine the state of dynamic balance of the small intestine microbiota; 3) healthy aging characterize by hight degree of cooperation between the main members of the bacterial community, which ensures the stability of the system at a new level, as one of the mechanisms of adaptation of the organism. Thus, the using the methods of GCMS MM and optimal scaling, allows us to expand our understanding of the age-associated trajectory of changes in the small intestine microbiota and its cooperation with the immune and neuroendocrine systems within the metaorganism, which can be used in the development of new methods of therapy of an infectious and non-infectious diseases.

scholarly journals Gut Microbiota: Critical Controller and Intervention Target in Brain Aging and Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Hui Li ◽  
Junjun Ni ◽  
Hong Qing
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Healthy Aging ◽  
Brain Aging ◽  
Current Trend ◽  
The Body ◽  
Dietary Interventions ◽  
Age Related ◽  
Functional Features ◽  
The Brain

The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it continues to mature until adulthood, when it comprises more stable and diverse microbial species. Meanwhile, as the physiological functions of the human body deteriorated with age, which may be a result of immunosenescence and “inflammaging,” the guts of elderly people are generally characterized by an enrichment of pro-inflammatory microbes and a reduced abundance of beneficial species. The gut microbiota affects the development of the brain through a bidirectional communication system, called the brain-gut-microbiota (BGM) axis, and dysregulation of this communication is pivotal in aging-related cognitive impairment. Microbiota-targeted dietary interventions and the intake of probiotics/prebiotics can increase the abundance of beneficial species, boost host immunity, and prevent gut-related diseases. This review summarizes the age-related changes in the human gut microbiota based on recent research developments. Understanding these changes will likely facilitate the design of novel therapeutic strategies to achieve healthy aging.

scholarly journals Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians

2019 ◽  
Vol 116 (48) ◽  
pp. 24242-24251 ◽  
Author(s):  
Kosuke Hashimoto ◽  
Tsukasa Kouno ◽  
Tomokatsu Ikawa ◽  
Norihito Hayatsu ◽  
Yurina Miyajima ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cd4 T Cells ◽  
Healthy Aging ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Cell Receptor ◽  
Peripheral Blood Mononuclear ◽  
Age Related

Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from 7 supercentenarians and 5 younger controls. We identified a marked increase of cytotoxic CD4 T cells (CD4 cytotoxic T lymphocytes [CTLs]) as a signature of supercentenarians. Furthermore, single-cell T cell receptor sequencing of 2 supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15 to 35% of the entire CD4 T cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Indeed, CD4 CTLs extracted from supercentenarians produced IFN-γ and TNF-α upon ex vivo stimulation. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.

Physiology of Geriatrics

2019 ◽  
Author(s):  
Christina M. Matadial
Keyword(s):  
Healthy Aging ◽  
Postoperative Cognitive Dysfunction ◽  
The Elderly ◽  
Adverse Outcomes ◽  
The Body ◽  
Chronic Obstructive ◽  
Medical Conditions ◽  
Compensatory Mechanisms ◽  
Obstructive Pulmonary Disease ◽  
Age Related

The aging population is growing and life expectancy is prolonged. The elderly population is able to enjoy prolonged life with good management of their chronic conditions. Many elderly do not have medical conditions but we still see a decline in their organ function and physiologic reserve that weighs in on their daily living. As well these changes in anatomy, physiology and chemistry puts them at risk of developing medical conditions and experience adverse outcomes during surgery and anesthesia. The central nervous, cardiovascular, respiratory, hepatic and renal systems all work together and are affected as a whole with aging causing physiologic changes but also compensatory mechanisms. In this review we will study the aging physiology of the body and touch on its implications in anesthesia. This review contains 5 figures, 3 tables, and  55 references. Keywords: Healthy aging, age-related changes, Postoperative cognitive dysfunction, diastolic dysfunction, vascular stiffening, ventricular arterial coupling, Chronic obstructive pulmonary disease, Spirometry, Glomerular Filtration Rate, hallmarks of aging

Hormesis and vitagenes in aging and longevity: mitochondrial control and hormonal regulation

2013 ◽  
Vol 16 (2) ◽  
Author(s):  
Carolin Cornelius ◽  
Antonio Graziano ◽  
Edward J. Calabrese ◽  
Vittorio Calabrese
Keyword(s):  
Heat Shock ◽  
Life Span ◽  
Stress Responses ◽  
Hormonal Regulation ◽  
Healthy Aging ◽  
Ovarian Function ◽  
Late Onset ◽  
Patient Treatment ◽  
Average Life Span ◽  
Age Related

AbstractAverage life span has increased because of medical and environmental factors, but maximal life span remains unchanged. Understanding the mechanisms of aging will help to reduce age-related morbidity and facilitate healthy aging. Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production or infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Age-related hypogonadism has been referred to as andropause or late-onset hypogonadism (LOH), with LOH considered to be the most suitable term for this condition. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. During aging, a gradual decline in the potency of the heat shock response occurs, and this may prevent the repair of protein damage. Thus, the interest in developing pharmacological agents capable of inducing stress responses is growing within the broad frame of hormesis, which underlie strategies for optimal patient treatment of numerous diseases. Vitagenes encode for heat shock proteins, thioredoxin, and sirtuin protein systems. Nutritional antioxidants have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. Here, we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against bioenergetic defects leading to degeneration and cell death with consequent impact on longevity processes.

scholarly journals Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Alexandra Barbouti ◽  
Panagiotis V. S. Vasileiou ◽  
Konstantinos Evangelou ◽  
Konstantinos G. Vlasis ◽  
Alexandra Papoudou-Bai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Cellular Senescence ◽  
The Body ◽  
Cell Mediated Immunity ◽  
Thymic Involution ◽  
Systemic Autoimmunity ◽  
Thymus Involution ◽  
Age Related ◽  
Regulatory Functions

The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed “thymic involution.” A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

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