Current Aging Science - Volume 10, Issue 4, 2017

The process of human ageing is significantly dependent upon events which are currently shaping humanity. One such event is the seemingly inexorable progress of technology, and specifically, digital communications technology. Technology and biology are tightly interconnected, and this has a direct relevance on how our own ageing mechanisms are evolving and adapting to the change. One way technology may affect biological ageing is based on the concept of information exposure which acts as a hormetic stimulus and up-regulates neuronal stress response pathways. In this way, neurons become increasingly more likely to acquire repair resources and function for longer, with a consequent overall improvement in healthy lifespan. At the same time, germline repair mechanisms may need to be downgraded in order to accommodate a tradeoff: a corresponding escalation of repairs in neurons. In this Opinion paper, it is discussed that how a meaningful and intentional integration with technology, which hormetically challenges our cognition, may redress the conflict for resources between the soma and the germline, and result in a reduction of age-related dysfunction in the subjects.

Background: Aging is the inevitable fate of all living organisms, but the molecular basis of physiological aging is poorly understood. Oxidative stress is believed to play a key role in the aging process. In addition to Reactive Oxygen Species (ROS), Reactive Nitrogen Species (RNS) are generated during aerobic metabolism in living organisms. Although protein damage and functional modification by ROS have been demonstrated in details, fewer studies have been reported on protein damage by RNS and its implication in the aging process. Proteins undergoing tyrosine nitration are associated with pathophysiology of several diseases, as well as physiological aging. The purpose of the current review article is to provide a brief summary of the biochemical mechanisms of tyrosine nitration, methodologies used for the detection of these modified proteins, effect of RNS induced post translational modification on biological functions and the putative role of tyrosine nitrated proteins in the aging process. Methods: Published studies on the role of RNS in age related functional alteration of various organs/ tissues were critically reviewed and evaluated. Results: Covalent modification of various proteins by tyrosine nitration is associated with modification of biological functions of various organs/tissues such as skeletal muscle, heart, brain and liver due to aging. Conclusion: This information will be helpful to further investigate the interplay of different biochemical pathways and networks involved in the tyrosine nitration of various proteins due to aging with the ultimate goal to prevent the detrimental effects of RNS on the functional activities of these proteins.

Background: Acute symptomatic seizures and epileptic disorders are frequent health problems of elderly patients. An early and reliable distinction of the seizure etiology is important to ensure adequate treatment, and to prevent unwarranted diagnostic and therapeutic procedures. Methods: We review the current literature based on a MEDLINE search, describe age-related problems in detail, with particular attention to clinical practice, discuss possible criteria and potential pitfalls for diagnostics, and provide a compilation of etiologic factors for acute symptomatic seizures. Results: The most common causes of acute symptomatic seizures - acute cerebrovascular disorders, metabolic disorders, traumatic brain injury, meningo-encephalitis, cerebral tumors, and withdrawal of alcohol and other central agents - are well-defined and seem to permit straightforward diagnostic and therapeutic strategies. The current classification of seizures and epileptic syndromes apparently provides clear definitions. However, multiple age-related risk factors, as well as a reduced discriminatory power of clinical and technical diagnostic criteria can make the distinction difficult. Conclusion: Typical age-related problems are incomplete or missing medical history, dementia, oligosymptomatic seizures, inconclusive EEG and cerebral imaging results, multiple pathological findings and comorbidity with ambiguous significance, confounding sleep disorders, intake of proconvulsive drugs, and psychogenic seizures. All diagnostic and therapeutic decisions need to be based on an integrative and individual approach that includes diagnostic findings and risk factors, the intake of medications and other agents, and the social situation of the elderly patient.

Background: Aging involves gradual, multisystemic Physiological Dysregulation (PD) which increases risk of age-related comorbidities. Ability to quantify age-related PD could provide insights into biological mechanisms underlying the aging process. One approach to measuring PD exploits the fact that increasing PD manifests as a gradual deviation of physiological parameters away from normal levels. A recent geometric approach for quantifying PD uses Mahalanobis distance to measure the extent to which an individual's physiological parameters (measured via biomarkers from clinical blood biochemistry panels) deviate from normal levels. While useful, this approach has shortcomings that may impact its accuracy, primarily the incorrect assumption of multivariate normality among biomarkers, and identical weighting of biomarkers. Herein, we develop a more robust multivariate distance-based measure of PD. Method: Proximity matrices induced by survival tree ensembles (Random Survival Forests) were used to compute a robust distance metric for quantifying how abnormal an individual's biomarker profile is. This approach requires no distributional assumptions and allows differential weighting of biomarkers based on association with mortality. Using receiver operating characteristic analysis and model fit statistics we compared performance of our measure to the standard approach based on Mahalanobis distance. Results & Conclusion: Our new metric showed statistically significant improvements in predicting mortality, health status and biological age, compared to the standard approach. Additional advantages offered by our method are the ability to handle missing values in biomarkers and to accommodate categorical risk factors. These results suggest our approach could provide greater precision in the evaluation of PD, which could enable better characterization of the extent and impact of degenerative processes resulting from aging.

Bacground: This article tackles social support as a meta-variable that is reinforced by a set of social variables, which correlate and act as predictors of social welfare and life quality of the older person. Objective: The objective of the study is to know how social support, networks and social contacts can influence the health of the elderly person, especially if these are interrelated factors. Method: The population studied are individuals from both sexes living in Toledo (Spanish people) and who were 65 years of age or over. Several scales were applied to assess the frequency of and the degree of satisfaction with perceived social support received from different sources in relation to social support. The co relational analysis showed significant positive associations between scores and measures of and social support, social relations, contact and social networks. Results: We conclude that the support in general is very good, over 90% of people from the sample have someone who would help if needed. Social and health factors are interrelated with social support. Social contact can also be considered as a life quality estimate. He progressive loss of contact over the years is a social factor that affects the quality of life. Conclusion: The meta-analysis we find that social support and the emotional factor, along with social interactions, have powerful effects on preventing morbidity and mortality, which are important social indicators. We conclude that social support based on positive social interactions provides an optimal state of health in the older person.

Background: Cytoskeleton anchoring of conformational mutant-like p53 is prominent in human senescent cells. The present research investigated the structural basis of vimentin cytoskeleton- anchoring of human p53. Method: GFP-fused wild type p53, mutant p53, those of the various truncated isoforms including p53β and p47, were expressed in the vimentin-expressing cells: mouse fibroblasts, COS-7 cells, young and senescent human fibroblasts, and HeLa cells (non-vimentin-expressing). Result: A cancer-specific mutant p53V143A-GFP expressed in mouse fibroblasts, exclusively anchored on the vimentin cytoskeleton. Class I mutant p53R175C-GFP and class II mutant p53R175S-GFP localized in the nuclei of COS-7 cells. A class III mutant p53R175X-GFP (X: D, F, W or Y), cancer-specific mutant p53V143A-GFP and p53R249S-GFP, exclusively anchored on the vimentin cytoskeleton of COS-7 cells. The deletions of p53R249S and p53V143A at the Cterminus (ΔC63) exclusively promoted the nuclear import of the deleted mutant p53 in COS-7 and HeLa cells, whereas the deletions at the N-terminus (ΔN40) or C-terminus (ΔC33) were ineffective. Thus, the cancer-specific mutant p53R249S and p53V143A adopt distinct mutant conformation and thereby the C-terminal region (aa331-360) potently interacts with the vimentin cytoskeleton and HeLa cells' cytoskeleton. Wild type p53-GFP exclusively localized in the nuclei of growing young fibroblast, in contrast to the significant cytoplasmic retention in senescent human fibroblasts. The deletion of p53 at the N-terminus or at the C-terminus (ΔN40 or ΔC63) results in a significant nuclear import of the shorter isoforms, p53β and p47. Conclusion: Senescent fibroblasts promote p53 to adopt a hotspot mutant like-conformation which significantly overrides the nuclear import due to the potent cytoskeleton-anchoring. Interestingly, the shorter p53 isoforms can escape from the cytoskeleton-anchoring.

Background: The thumb plays a critical role for manual tasks during the activities of daily life and the incidence of neurological or musculoskeletal disorders affecting the voluntary movements of the thumb is high in the elderly. There is currently no tool to assess repetitive motor sequencing of the thumb during ageing. Objectives: To report a novel procedure (the Click Test) assessing the effects of ageing on fast motor sequencing of the thumb. Method: Healthy subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years; F/M: 151/101) were asked to perform fast repeated flexion/extension movements of the thumb using a mechanical counter. Results: Motor performances (assessed by the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly decreased as a function of age for both the dominant (age effect; p< 0.0001 for 15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec). The number of clicks was significantly higher in males (gender effect; p<0.001) and was higher on the dominant side as compared to the non-dominant side (handedness effect: p<0.001). The Click Test is characterized by high repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra-rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high inter-rater reproducibility (Pearson's product correlation ranging from 0.85 to 0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly correlated in terms of relative performances with the box and block test and the 9-hole peg test (positive linear correlation with the results of the box and block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand; negative linear correlation with the results of the 9-hole peg test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand). Conclusion: The Click Test is an entirely novel and very low cost tool to reliably discriminate the ageing effects upon the performances during fast repetitive motor sequencing of the thumb. The potential clinical and research applications for motor functions are multiple, especially in acute and chronic neurological disorders affecting the thumb as well as in the field of rheumatology and orthopedics.