physiological ageing
Recently Published Documents


TOTAL DOCUMENTS

61
(FIVE YEARS 18)

H-INDEX

15
(FIVE YEARS 1)

Author(s):  
Tatjana Lazarevic ◽  
Zoran Kovacevic

Abstract Premature loss of functional integrity of the nervous system in chronic renal failure (CRF) as a consequence of persistent biological activities of the general uremic milieu is almost identical to its structural and functional involution during the process of physiological ageing, but disproportionate and independent of chronological age. In the hyperuremic status of CRF (urea - carbamide), forced carbamylation, as a non-enzymatic post-translational modification (NEPTM) of proteins and amino acids, by changing their biological properties and decreasing proteolysis capacity, represents pathogenetic potential of intensified molecular ageing and accelerated, pathological involution. Physiological predisposition and the exposure of neuropathy before complications of other organs and organ systems in CRF, due to the simultaneous and mutually pathogenetically related uremic lesion and the tissue and vascular segment of the nervous system, direct interest towards proteomic analytical techniques of quantification of carbamylated products as biomarkers of uremic neurotoxicity. Hypothetically, identical to the already established applications of other NEPTM products in practice, they have the potential of clinical methodology in the evaluation of uremic neuropathy and its contribution to the general prediction, but also to the change of the conventional CRF classification. In addition, the identification and therapeutic control of the substrate of accelerated involution, responsible for the amplification of not only neurological but also general degenerative processes in CRF, is attractive in the context of the well-known attitude towards aging.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1002
Author(s):  
Jürgen Götz ◽  
Gina Richter-Stretton ◽  
Esteban Cruz

Physiological and pathological ageing (as exemplified by Alzheimer’s disease, AD) are characterized by a progressive decline that also includes cognition. How this decline can be slowed or even reversed is a critical question. Here, we discuss therapeutic ultrasound as a novel modality to achieve this goal. In our studies, we explored three fundamental strategies, (i) scanning ultrasound on its own (SUSonly), (ii) therapeutic ultrasound in concert with intravenously injected microbubbles (which transiently opens the blood–brain barrier, SUS+MB), and (iii) SUS+MB in combination with therapeutic antibodies (SUS+MB+mAb). These studies show SUS+MB effectively clears amyloid and restores memory in amyloid-depositing mice and partially clears Tau and ameliorates memory impairments in Tau transgenic mice, with additional improvements found in combination trials (SUS+MB+mAb). Interestingly, both SUSonly and SUS+MB restored the induction of long-term potentiation (LTP, electrophysiological correlate of memory) in senescent wild-type mice. Both lead to increased neurogenesis, and SUSonly, in particular, resulted in improved spatial memory. We discuss these findings side-by-side with our findings obtained in AD mouse models. We conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may present a treatment option not only for AD but also for enhancing cognition in physiological ageing.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 512
Author(s):  
Nady Braidy ◽  
Maria D. Villalva ◽  
Ross Grant

Nicotinamide adenine dinucleotide (NAD+) and its metabolome (NADome) play important roles in preserving cellular homeostasis. Altered levels of the NADome may represent a likely indicator of poor metabolic function. Accurate measurement of the NADome is crucial for biochemical research and developing interventions for ageing and neurodegenerative diseases. In this mini review, traditional methods used to quantify various metabolites in the NADome are discussed. Owing to the auto-oxidation properties of most pyridine nucleotides and their differential chemical stability in various biological matrices, accurate assessment of the concentrations of the NADome is an analytical challenge. Recent liquid chromatography mass spectrometry (LC-MS) techniques which overcome some of these technical challenges for quantitative assessment of the NADome in the blood, CSF, and urine are described. Specialised HPLC-UV, NMR, capillary zone electrophoresis, or colorimetric enzymatic assays are inexpensive and readily available in most laboratories but lack the required specificity and sensitivity for quantification of human biological samples. LC-MS represents an alternative means of quantifying the concentrations of the NADome in clinically relevant biological specimens after careful consideration of analyte extraction procedures, selection of internal standards, analyte stability, and LC assays. LC-MS represents a rapid, robust, simple, and reliable assay for the measurement of the NADome between control and test samples, and for identifying biological correlations between the NADome and various biochemical processes and testing the efficacy of strategies aimed at raising NAD+ levels during physiological ageing and disease states.


2021 ◽  
Author(s):  
Clement Crochemore ◽  
Claudia Chica ◽  
Paolo Garagnani ◽  
Giovanna Lattanzi ◽  
Steve Horvath ◽  
...  

Cockayne syndrome (CS) and UV-sensitivity syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and chromatin remodelling proteins CSA or CSB, but only CS patients display a progeroid and neurodegenerative phenotype. As epigenetic modifications constitute a well-established hallmark of ageing, we characterized genome-wide DNA methylation (DNAm) of fibroblasts from CS versus UVSS patients and healthy donors. The analysis of differentially methylated positions and regions revealed a CS-specific epigenetic signature, enriched in developmental transcription factors, transmembrane transporters, and cell adhesion factors. The CS-specific signature compared to DNAm changes in other progeroid diseases and regular ageing, identifyied commonalities and differences in epigenetic remodelling. CS shares DNAm changes with normal ageing more than other progeroid diseases do, and according to the methylation clock CS samples show up to 13-fold accelerated ageing. Thus, CS is characterized by a specific epigenomic signature that partially overlaps with and exacerbates DNAm changes occurring in physiological aging. Our results unveil new genes and pathways that are potentially relevant for the progeroid/degenerative CS phenotype.


2021 ◽  
pp. 1-15
Author(s):  
Alexei Verkhratsky

Astroglia are neural cells of ectodermal, neuroepithelial origin responsible for homoeostasis and defence of the central nervous system (CNS). Ageing reduces the functional capacity of all organs, so does that of the nervous system, the latter is evident in the reduction of cognitive abilities, learning and memory. At the same time the progression of these deficits is very much individual and lifestyle dependent, indicating operation of mechanisms counterbalancing age-dependent decline. In physiological ageing astrocytes undergo morphological atrophy and functional asthenia; astrocytic paralysis facilitates progression of age-dependent neurodegenerative disorders. Astroglial status and homoeostatic capabilities are influenced by lifestyle including intellectual engagement, social interactions, physical exercise, and healthy diet. Maintenance of healthy lifestyle is paramount for cognitive longevity.


Author(s):  
Marloes Verkerke ◽  
Elly M. Hol ◽  
Jinte Middeldorp

AbstractAgeing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE ε4 is genetically the strongest risk factor for Alzheimer’s disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain.


Author(s):  
Juan A. Sepulveda ◽  
Andrew J. Anderson ◽  
Joanne M. Wood ◽  
Allison M. McKendrick

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
A Shono ◽  
K Matsumoto ◽  
N Yamada ◽  
K Kusunose ◽  
M Suzuki ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background  Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose  The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods  A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, >65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.).  Results  The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P < 0.001, respectively). Although baseline LV ejection fraction and cardiac output were quite comparable between groups, E/e’ ratio significantly increased with with ageing (ANOVA P < 0.001, Fig.). During LPP stress, E/e’ ratio significantly increased in the middle-aged and elderly groups (from 8.8 ± 2.7 to 9.7 ± 3.3, and from 11.4 ± 2.4 to 13.0 ± 2.2, P < 0.05, respectively), which was further deteriorated in HFpEF (from 16.8 ± 5.8 to 18.0 ± 7.6, P < 0.05). On the other hand, stroke volume index (SVi) significantly increased in each healthy group during LPP stress (young; from 45 ± 10 to 50 ± 11 mL/m², middle-age; from 39 ± 7 to 44 ± 6 mL/m² and elderly; from 37 ± 7 to 43 ± 8 mL/m², all P < 0.001), while SVi failed to increase in the HFpEF group (from 45 ± 13 to 45 ± 14 mL/m², P = 0.60). In a multivariate logistic regression analysis, LVMI (hazard ratio; HR 1.055, P < 0.05), baseline E/e’ (HR 1.444; P < 0.05), and ΔSVi (HR 0.755; P < 0.05) during LPP stress were the independent parameters that characterised overt HFpEF. Conclusions  Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.


2021 ◽  
Vol 5 (3) ◽  
pp. 66-73
Author(s):  
Emmanouil Dimonitsas

Aim: The physiological ageing process causes significant changes in the extracellular matrix (ECM) of the neck skin, which are the first signs of ageing witness for women. We are inspired by a young woman, who suffers from a rare genetic disorder called pseudoxanthoma elasticum (PXE), which manifests irregular, thickened, fragmented and haphazardly orientated elastic fibers. We herein present a combination of three different therapies (laser skin resurfacing, type I horse collagen boosters and platelet rich plasma)as an approach to ameliorate neck skin sagging. Methods: A 28-year-old Roma woman with a clinically diagnosed PXE, verified by ophthalmologic evidence and skin biopsy, underwent 3 sessions of this combined protocol every 3 weeks. One month after the last treatment session, a new biopsy was taken. During this period, the patient was encouraged for daily topical application of collagen mousse and vitamin C combined with sun block SPF50, along with limited exposure to sunlight. Results: Clinical assessment supported by photographic documentation was performed at each session. Severe changes in hydration and tightening of the neck skin were obvious 3 weeks after the second session, although the verification of the results was substantiated with the pathology of the post treatment skin biopsy obtained 1 month following the completion of the protocol. The elastic fibers in the mid-dermis were dense, non-fragmented and parallel oriented. The aesthetic performance was evident until the final follow-up visit. Conclusions: Nowadays, the primary goal of aesthetic medical research is oriented to the dermis bio-reconstruction, where specific treatments try to improve the dermis quality from the inside to repair imperfections of skin ageing. The key of success is attributed to the best possible treatment combination capable of fibroblast stimulation.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sofie De Moudt ◽  
Jhana O Hendrickx ◽  
Dorien G De Munck ◽  
Arthur J Leloup ◽  
Wim Martinet ◽  
...  

Introduction: Arterial stiffness (AS) has gained much recognition as a hallmark and independent predictor of cardiovascular (CV) events. Although generally assumed to be an adaptive response to increased blood pressure (BP), AS precedes hypertension in at least two experimental mouse models, thus revealing an incomplete understanding of AS pathophysiology. Methods: The current study presents the longitudinal CV characterization of spontaneously ageing C57Bl6 mice (2, 4, 6, 9, 12 and 24-month old) (male, n>8). In vivo analysis of peripheral BP (Coda), aortic pulse wave velocity (aPWV, Vevo2100), and echocardiography (Vevo2100) was combined with ex vivo aortic studies of isometric reactivity (organ baths) and AS measurements in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC). (Data are presented as mean ± SEM.) Results: In vivo and ex vivo characterisation confirms that aortic stiffness precedes peripheral BP alterations in spontaneously ageing C57Bl6 mice, with significantly and gradually increasing aPWV (Fig.A) and isobaric Peterson modulus (Ep) (Fig.B) from 6-month of age onward. Thereafter, cardiac hypertrophy was observed at 9-months of age (Fig.C), and peripheral BP measurement reveals elevated pulse pressure at 24-months (30% increase vs. all other ages) (Fig.D). Ex vivo investigation of the thoracic aorta shows increased contractions to phenylephrine (PE) in old (6-24 month) vs. young (2-4 month) mice (Fig.E,F) with an increased contribution of voltage-gated calcium channel (VGCC) (Fig.G,H) with age. Remarkably, no differences were observed on endothelial function, meaning that all changes occur on the level of the vascular smooth muscle cell (VSMC). Conclusions: Physiological ageing of VSMC results in high PE contractions, increased VGCC activity, and the development of significant arterial stiffening by 6-months of age. AS thereby precedes the development of peripheral BP alterations by 18 months.


Sign in / Sign up

Export Citation Format

Share Document