scholarly journals Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates

2021 ◽  
Vol 13 ◽  
Author(s):  
Shannon N. Leslie ◽  
Jean Kanyo ◽  
Dibyadeep Datta ◽  
Rashaun S. Wilson ◽  
Caroline Zeiss ◽  
...  

Age is the most significant risk factor for Alzheimer’s disease (AD), and understanding its role in specific aspects of AD pathology will be critical for therapeutic development. Neurofibrillary tangles composed of hyperphosphorylated tau are a quintessential hallmark of AD. To study age-related changes in tau phosphorylation, we developed a simple, antibody-free approach for single shot analysis of tau phosphorylation across the entire protein by liquid-chromatography tandem mass spectrometry. This methodology is species independent; thus, while initially developed in a rodent model, we utilized this technique to analyze 36 phosphorylation sites on rhesus monkey tau from the prefrontal cortex (PFC), a region vulnerable to AD-linked degeneration. Data are available via ProteomeXchange with identifier PXD027971. We identified novel, age-related changes in tau phosphorylation in the rhesus monkey PFC and analyzed patterns of phosphorylation change across domains of the protein. We confirmed a significant increase and positive correlation with age of phosphorylated serine 235 tau and phosphorylated serine 396 tau levels in an expanded cohort of 14 monkeys. Histology showed robust labeling for tau phosphorylated at these sites in vulnerable layer III pyramidal cells in the PFC. The results presented in this study suggest an important role of the natural aging process in tau phosphorylation in rhesus monkey.

2020 ◽  
Author(s):  
Jonathan J. Fox ◽  
Takao Hashimoto ◽  
Héctor I. Navarro ◽  
Alejandro J. Garcia ◽  
Benjamin L. Shou ◽  
...  

SUMMARYAging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective.


2013 ◽  
Vol 25 (6) ◽  
pp. 1454-1468 ◽  
Author(s):  
J. I. Luebke ◽  
M. Medalla ◽  
J. M. Amatrudo ◽  
C. M. Weaver ◽  
J. L. Crimins ◽  
...  

1995 ◽  
Vol 16 (6) ◽  
pp. 939-946 ◽  
Author(s):  
Greg A. Gerhardt ◽  
Wayne A. Cass ◽  
Michael Henson ◽  
Zhiming Zhang ◽  
Aliza Ovadia ◽  
...  

Vitreous is an important ocular structure in the normal physiology and pathologic conditions of the posterior segment. Vitreous is a gel-like composite structure and forms an extracellular matrix that occupies the biggest space in the eye. The healthy vitreous gel reduces oxygen tension and protects vitreous, retina, and lens from oxidative damage. Vitreous plays an important role in the refraction of the eye, preserving the transparency with regular interaction of the macromolecules contained therein. Vitreous suffer from continuous physical tension and this results in important changes. Particularly age-related degeneration in the structure of the vitreous gel leads to a decrease in vitreoretinal adhesion. As part of natural aging, the posterior vitreous detachment process may become pathologic when the vitreoretinal interface weakens simultaneously with vitreous liquefaction. In this process, vision-threatening diseases such as vitreomacular adhesion, vitreomacular traction, and macula hole may appear.


2020 ◽  
Vol 32 (S1) ◽  
pp. 173-173
Author(s):  
Catarina Pedro ◽  
Mariana Duarte ◽  
Beatriz Jorge ◽  
Daniela Freitas

Introduction:Personality and emotions have not been studied as thoroughly as cognition in old age. Recent research suggests personality changes across the entire life span, through middle age and even into old age. Thus, the previous assumption of stability in personality traits from early adulthood has been challenged and novel approaches to the study of personality development have emerged.Objectives:The aim of this presentation is to describe the effects of the ageing process in personality and emotions.Methods:A non-systematic review of the literature was performed on PubMed, PsycINFO and Web of science using selected keywords.Results:When older adults compare their current and past selves, they usually perceive a subjective growth in personality. Descriptive research suggests that the big five personality characteristics (neuroticism, extraversion, openness, agreeableness and conscientiousness) remain generally stable over the lifespan, despite variations in life experiences. Some studies revealed age-related linear decrease in extraversion. One of the studies found that hearing impairment, already identified as a significant risk factor for social isolation, was related to this decline in extraversion. Although levels of neuroticism tends to go down over the course of adulthood, the increased vulnerabilities that accompany old age may amplify neurotic traits, increasing worries about physical health and memory, common features of depression in the elderly. Emotions, relative to more neutral knowledge and skills, increase in later years. Elderly have better control over emotions than do younger adults, they reason more flexibly about emotion-laden dilemmas and remember emotionally charged information better than neutral facts. Older people also rely more often on emotion-focused forms of coping, as opposed to active, problem-solving approaches.Conclusions:Core features of personality seem to remain relatively stable throughout adulthood and any marked change in mood or social behavior may indicate a disorder. However, more subtle reordering of personal priorities and shifts in coping styles are common with normal ageing. The richness of emotional processing in older persons runs counter to the generally declining patterns seen in many cognitive and physical skills.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Pooja Shivshankar

Streptococcus pneumonia, (Spn, the pneumococcus), is the leading cause of community-acquired pneumonia (CAP) and is responsible for 15–40% deaths in the elderly worldwide. A primed inflammatory status is a significant risk factor for the increased severity of infectious diseases among the elderly (≥65 years of age). Studies have shown that expression of host receptors that the pneumococci bind to invade the tissues are increased thereby increasing the susceptibility to pneumococcal challenge in aged mice. Cellular senescence, an age-related phenomenon that leads to cell cycle arrest may also contribute to increased inflammation in aged mice. Evidence of cellular senescence in aged lungs of humans and mice adds credits to the concept of inflammaging and enhanced bacterial ligands expression during aging. Furthermore, cell senescence has been shown to occur in age-associated lung pathologies such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) that may predispose the elderly to pathogenic assaults, including S. pneumoniae. This review highlights the aspects of: chronic inflammation in the aged population; contribution of cellular senescence to age-associated inflammation and their impact on host receptor expression; and, increased susceptibility of fibrosis and emphysematous lesions-bearing lungs to microbial infections.


2021 ◽  
Vol 13 ◽  
Author(s):  
Anna Gasiorowska ◽  
Malgorzata Wydrych ◽  
Patrycja Drapich ◽  
Maciej Zadrozny ◽  
Marta Steczkowska ◽  
...  

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.


2020 ◽  
Author(s):  
Raquel R. Martins ◽  
Mazen Zamzam ◽  
Mariya Moosajee ◽  
Ryan Thummel ◽  
Catarina M. Henriques ◽  
...  

ABSTRACTAgeing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions. Yet, the impact of ageing on MG regenerative capacity has not yet been considered. Here we show that the zebrafish retina undergoes telomerase-independent age-related neurodegeneration. Yet, this progressive neuronal loss in the ageing retina is insufficient to stimulate the MG regenerative response. Instead, age-related neurodegeneration leads to MG gliosis and loss of vision, similarly to humans. Nevertheless, gliotic MG cells retain Yap expression and the ability to regenerate neurons after acute light damage. Therefore, we identify key differences in the MG response to acute versus chronic damage in the zebrafish retina and show that aged gliotic MG can be stimulated to repair damaged neurons in old age.SUMMARYOur data suggest there are key differences between mechanisms driving regeneration in response to acute damage versus age-related chronic damage. It may be that either the number of cells dying in natural ageing is not enough to stimulate MG to proliferate, or the low number of microglia and respective signals released are not sufficient to trigger MG proliferation. Importantly, we show that gliotic MG cells can be stimulated to repair damaged neurons in old zebrafish retina.


1997 ◽  
Vol XXIX (3-4) ◽  
pp. 95-97
Author(s):  
Е. A. Antipenko ◽  
L. M. Anisimova ◽  
А. V. Deryugina ◽  
А. V. Gustov ◽  
V. N. Krylov

Difficulties in treating discirculatory encephalopathy (DE) in the elderly are caused by a combination of degenerative and vascular processes, which mutually burden each other. The development of the disease against the background of natural aging of the body makes it necessary to take into account age-related changes in the reactivity of the body, a decrease in its adaptive capabilities, and a violation of the mechanisms of autoregulation [6]. This whole complex of pathological changes requires a special therapeutic approach that considers the body as a single functional system. It can be assumed that drugs of a non-specific plan will be effective, mobilizing the internal reserves of an aging organism.


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