scholarly journals Functional Aging in Male C57BL/6J Mice Across the Life-Span: A Systematic Behavioral Analysis of Motor, Emotional, and Memory Function to Define an Aging Phenotype

2021 ◽  
Vol 13 ◽  
Author(s):  
Shuichi Yanai ◽  
Shogo Endo
Keyword(s):  
Life Span ◽  
Memory Function ◽  
Laboratory Mouse ◽  
Gait Velocity ◽  
Prime Model ◽  
Human Aging ◽  
Functional Changes ◽  
Functional Capabilities ◽  
Age Related ◽  
Long Line

Aging is characterized generally by progressive and overall physiological decline of functions and is observed in all animals. A long line of evidence has established the laboratory mouse as the prime model of human aging. However, relatively little is known about the detailed behavioral and functional changes that occur across their lifespan, and how this maps onto the phenotype of human aging. To better understand age-related changes across the life-span, we characterized functional aging in male C57BL/6J mice of five different ages (3, 6, 12, 18, and 22 months of age) using a multi-domain behavioral test battery. Spatial memory and physical activities, including locomotor activity, gait velocity, and grip strength progressively declined with increasing age, although at different rates; anxiety-like behaviors increased with aging. Estimated age-related patterns showed that these functional alterations across ages are non-linear, and the patterns are unique for each behavioral trait. Physical function progressively declines, starting as early as 6 months of age in mice, while cognitive function begins to decline later, with considerable impairment present at 22 months of age. Importantly, functional aging of male C57BL/6J mouse starts at younger relative ages compared to when it starts in humans. Our study suggests that human-equivalent ages of mouse might be better determined on the basis of its functional capabilities.

III. Senescent enteric nervous system: lessons from extraintestinal sites and nonmammalian species

2002 ◽  
Vol 283 (5) ◽  
pp. G1020-G1026 ◽  
Author(s):  
John W. Wiley
Keyword(s):  
Life Span ◽  
Cellular Function ◽  
Colonic Transit ◽  
Advanced Age ◽  
Physiological Aging ◽  
Functional Changes ◽  
Age Related ◽  
Igf I ◽  
And Function ◽  
Kinase Expression

Functional changes in GI motility associated with advanced age include slowing of gastric emptying, decreased peristalsis, and slowing of colonic transit. These changes appear to be associated with region-specific loss of neurons and impaired function. The mechanism(s) underlying physiological aging are likely to be multifactorial. Alterations in specific signal transduction pathways have been reported at the level of the receptor and postreceptor events including kinase expression and function, mitochondrial function, and activation of the apoptosis cascade. Advanced age is associated with increased oxidative stress and its concomitant effects on cellular function. Whereas no specific genes have been causally linked to life span in mammals, studies involving nonmammalian species suggest that specific genes are involved in determining life span and age-related changes in cellular function. Caloric restriction is the only intervention shown to slow aging in a variety of species. Recent studies implicate a possible role for an insulin/IGF-I cascade in the region- and tissue-specific changes associated with physiological aging.

scholarly journals Enriching hippocampal memory function in older adults through real-world exploration

2019 ◽  
Author(s):  
Branden S. Kolarik ◽  
Shauna M. Stark ◽  
Samantha M. Rutledge ◽  
Craig E.L. Stark
Keyword(s):  
Older Adults ◽  
Real World ◽  
Memory Performance ◽  
Memory Function ◽  
Discrimination Index ◽  
Healthy Older Adults ◽  
Functional Changes ◽  
Age Related ◽  
Spatial Exploration

AbstractAge-related structural and functional changes in the hippocampus can have a severe impact on hippocampally-dependent memory performance. Here we test the hypothesis that a real-world spatial exploration intervention will improve hippocampally-dependent memory performance in healthy older adults. We found that following our intervention, participants’ lure discrimination index (LDI) was significantly higher than it was at baseline, while traditional recognition scores remained relatively unchanged. These results point to the viability of a spatial exploration intervention for improving hippocampally-dependent memory in older adults.

NATURAL AGE-RELATED COGNITIVE IMPAIRMENTS: OVERVIEW OF RECENT INVESTIGATIONS IN NON-HUMAN PRIMATES

2020 ◽  
pp. 23-33
Author(s):  
Д. Г. Семенов ◽  
А. В. Беляков
Keyword(s):  
Experimental Study ◽  
Life Span ◽  
Cognitive Functions ◽  
Cognitive Aging ◽  
Cognitive Impairments ◽  
Developed Countries ◽  
Human Aging ◽  
Age Related ◽  
Aging Mechanisms ◽  
The Brain

Старение человека сопровождается ослаблением когнитивных функций мозга. Актуальность изучения этого процесса, как и поиска путей его медицинской коррекции, возрастает в связи с увеличением средней продолжительности жизни в развитых странах. Нечеловекообразные приматы признаны наиболее подходящей биологической моделью для экспериментального изучения естественных механизмов когнитивного старения. В обзоре представлены последние данные, характеризующие поведенческие закономерности старения этих животных и соответствующие структурнофункциональные и молекулярно-клеточные корреляты. Описаны некоторые эффективные способы профилактики и терапии естественного старческого когнитивного ослабления. Human aging is followed by the weakening of cognitive functions of the brain. The relevance of the study of this process as well as the search for ways of its medical correction increases due to the rise of the middle life span in developed countries. Non-human primates are recognized as the most appropriate biological model for the experimental study of natural cognitive aging mechanisms. The review presents the latest data characterizing age-related behavioral patterns of these animals and the corresponding structural-functional and molecular-cellular correlates. Some effective ways preventing natural senile cognitive decline are highlighted.

scholarly journals WWC1 Genotype Modulates Age-Related Decline in Episodic Memory Function Across the Adult Life Span

2014 ◽  
Vol 75 (9) ◽  
pp. 693-700 ◽  
Author(s):  
John Muse ◽  
Matthew Emery ◽  
Fabio Sambataro ◽  
Herve Lemaitre ◽  
Hao-Yang Tan ◽  
...  
Keyword(s):  
Episodic Memory ◽  
Life Span ◽  
Memory Function ◽  
Adult Life ◽  
Adult Life Span ◽  
Age Related

scholarly journals Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatyana V. Sukhacheva ◽  
Natalia V. Nizyaeva ◽  
Maria V. Samsonova ◽  
Andrey L. Cherniaev ◽  
Artem A. Burov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Mitral Valve Regurgitation ◽  
Ultrastructural Level ◽  
Cardiomyocyte Hypertrophy ◽  
Myocardial Remodeling ◽  
Valve Regurgitation ◽  
Atrial Myocardium ◽  
Functional Changes ◽  
Age Related ◽  
Transitional Forms

AbstractTelocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3–25% biopsies of left (LAA) and 21.7–41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into “transitional forms” combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

scholarly journals Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 242
Author(s):  
Salvatore Nesci ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
Vittoria Ventrella ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Ros Generation ◽  
Protonmotive Force ◽  
Mitochondrial Oxidative Phosphorylation ◽  
F1fo Atp Synthase ◽  
Functional Changes ◽  
Age Related ◽  
Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Positive Emodiversity Buffers the Association Between Stress and Depressive Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 653-653
Author(s):  
Lizbeth Benson ◽  
Anthony Ong
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Life Span ◽  
Daily Diary ◽  
National Study ◽  
Younger Adults ◽  
Shannon's Entropy ◽  
Daily Experiences ◽  
Age Related ◽  
Optimal Functioning

Abstract Intensive measurements of individuals’ experiences allow for identifying patterns of functioning that may be markers of resilience, and whether such patterns differ across the life span. Using 8 daily diary reports collected in the second burst of the National Study of Daily Experiences (NSDE, n=848, age 34-84; 55%female), we examined whether positive emodiversity (Shannon’s entropy) attenuated the association between cumulative stressor exposure and depressive symptoms, and age-related differences therein. Results indicated age moderated the extent to which positive emodiversity attenuated the association between stress and depressive symptoms (b=0.11, p < .05). The attenuated association was strongest for younger adults with higher positive emodiversity, compared to those with lower positive emodiversity. For older adults, the association between stress and depressive symptoms was relatively similar regardless of their positive emodiversity. Implications pertain to for whom and in what contexts specific types of dynamic emotion experiences may promote optimal functioning and resilience.

scholarly journals Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

Gerontology ◽  
2016 ◽  
Vol 63 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Animal Models ◽  
Genetic Manipulation ◽  
Logic Gate ◽  
Therapeutic Interventions ◽  
Human Aging ◽  
Aging Research ◽  
Epigenome Editing ◽  
Related Disease ◽  
Age Related

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

scholarly journals Autobiographical Memory in Normal Ageing and Dementia

1991 ◽  
Vol 4 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Harvey J. Sagar ◽  
Edith V. Sullivan ◽  
Suzanne Corkin
Keyword(s):  
Memory Function ◽  
Early Adulthood ◽  
Normal Subjects ◽  
Elderly Subjects ◽  
Retrieval Cues ◽  
Age Related ◽  
Normal Ageing ◽  
Severity Of Dementia ◽  
And Control ◽  
Cue Words

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

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