The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia

Examining neural etiologic factors’role in the decline of neuromuscular function with aging is essential to our understanding of the mechanisms underlying sarcopenia, the age-dependent decline in muscle mass, force and power. Innervation of the skeletal muscle by both motor and sympathetic axons has been established, igniting interest in determining how the sympathetic nervous system (SNS) affect skeletal muscle composition and function throughout the lifetime. Selective expression of the heart and neural crest derivative 2 gene in peripheral SNs increases muscle mass and force regulating skeletal muscle sympathetic and motor innervation; improving acetylcholine receptor stability and NMJ transmission; preventing inflammation and myofibrillar protein degradation; increasing autophagy; and probably enhancing protein synthesis. Elucidating the role of central SNs will help to define the coordinated response of the visceral and neuromuscular system to physiological and pathological challenges across ages.This review discusses the following questions: (1) Does the SNS regulate skeletal muscle motor innervation? (2) Does the SNS regulate presynaptic and postsynaptic neuromuscular junction (NMJ) structure and function? (3) Does sympathetic neuron (SN) regulation of NMJ transmission decline with aging? (4) Does maintenance of SNs attenuate aging sarcopenia? and (5) Do central SN group relays influence sympathetic and motor muscle innervation?     

Age-related amyloidosis outside the brain: A state-of-the-art review

Inside and outside the brain, accumulation of amyloid fibrils plays key roles in the pathogenesis of fatal age-related diseases such as Alzheimer’s and Parkinson’s diseases and wild-type transthyretin amyloidosis. Although the incidence of all amyloidoses increases with age, for some types of amyloidosis aging is known as the main direct risk factor, and these types are typically diseases of elderly people. More than 10 different precursor proteins are known to cause age-associated amyloidosis; these proteins include amyloid β protein, α-synuclein, transthyretin, islet amyloid polypeptide, atrial natriuretic factor, and the newly discovered epidermal growth factor-containing fibulin-like extracellular matrix protein 1. Except for intracerebral amyloidoses, most age-related amyloidoses have been little studied. Indeed, in view of the increasing life expectancy in our societies, understanding how aging is involved in the process of amyloid fibril accumulation and the effects of amyloid deposits on the aging body is extremely important. In this review, we summarize current knowledge about the nature of amyloid precursor proteins, the prevalence, clinical manifestations, and pathogenesis of amyloidosis, and recent advances in our understanding of age-related amyloidoses outside the brain.     

Hippuric acid: Could became a barometer for frailty and geriatric syndromes?

Aging is a natural biological event that has some downsides such as increased frailty, decline in cognitive and physical functions leading to chronical diseases, and lower quality of life. There is therefore a pressing need of reliable biomarkers to identify populations at risk of developing age-associated syndromes in order to improve their quality of life, promote healthy ageing and a more appropriate clinical management, when needed. Here we discuss the importance of hippuric acid, an endogenous co-metabolite, as a possible hallmark of human aging and age-related diseases, summarizing the scientific literature over the last years. Hippuric acid, the glycine conjugate of benzoic acid, derives from the catabolism by means of intestinal microflora of dietary polyphenols found in plant-based foods (e.g. fruits, vegetables, tea and coffee). In healthy conditions hippuric acid levels in blood and/or urine rise significantly during aging while its excretion drops in conditions related with aging, including cognitive impairments, rheumatic diseases, sarcopenia and hypomobility. This literature highlights the utility of hippuric acid in urine and plasma as a plausible hallmark of frailty, related to low fruit and vegetable intake and changes in gut microflora.     

Matters of size: Roles of hyaluronan in CNS aging and disease

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.     

Inflammaging and Cannabinoids

Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging –a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.     

Musical enjoyment does not enhance walking speed in healthy adults during music-based auditory cueing

BackgroundRhythmic Auditory Stimulation (RAS) involves synchronizing footsteps to music or a metronome to improve gait speed and stability in patients with neurological disorders, such as Parkinson’s disease. However, responses to RAS vary across individuals, perhaps because of differences in enjoyment of the music or in musical abilities.Research questionIntuitively, musical enjoyment may influence gait responses to RAS, but enjoyment has not been systematically manipulated nor the effects empirically assessed. In addition, differences in beat perception ability are likely to influence gait responses to music, particularly when synchronizing to the beat. Therefore, we asked: how does music enjoyment alter gait, and do gait parameters differ between individuals with good versus poor beat perception ability, specifically when instructed to ‘walk freely’ versus ‘synchronize to the beat’?MethodYoung adults and older adults walked on a pressure sensor walkway in silence and to music that they had rated as either high or low in enjoyment, as well as a metronome. All stimuli were presented at 15 % faster than baseline cadence. Participants either walked freely to the music or synchronized to the beat.ResultsMusic enjoyment had no significant effects on gait in either younger or older adults. Compared to baseline, younger adults walked faster (by taking longer strides) to music than the metronome, whereas older adults walked faster (by taking more steps per minute) to the metronome than music. When instructed to synchronize vs. walk freely, young adults walked faster, but older adults walked slower. Finally, regardless of instruction type, young adults with poor beat perception took shorter and slower strides to the music, whereas older adults with poor beat perception took slower strides to the music.SignificanceBeat perception ability, instruction type, and age affect gait more than music enjoyment does, and thus should be considered when optimizing RAS outcomes.     

Effects of wearing a head-mounted display during a standard clinical test of dynamic balance

BackgroundThe use of virtual reality (VR) in clinical settings has increased with the introduction of affordable, easy-to-use head-mounted displays (HMDs). However, some have raised concerns about the effects that HMDs have on posture and locomotion, even without the projection of a virtual scene, which may be different across ages.Research questionHow does HMD wear impact the kinematic measures in younger and older adults?MethodsTwelve healthy young and sixteen older adults participated in two testing conditions: 1) TUG with no HMD and 2) TUG with an HMD displaying a scene of the actual environment (TUG_HMD). The dependent variables were the pitch, yaw, and roll peak trunk velocities (PTVs) in each TUG component, turning cadence, and the time to complete the TUG and its components – SIT-TO-STAND, TURN, WALK, and STAND-TO-SIT.ResultsWearing the HMD decreased turning cadence and pitch and yaw PTVs in all TUG components, decreased roll PTV in SIT-TO-STAND and TURN, and increased the time taken to complete all TUG components in all participants. Wearing the HMD decreased the pitch PTV in SIT-TO-STAND in older relative to younger adults.Wearing an HMD affected TUG performance in younger and older adults, which should be considered when an HMD is used for VR applications in rehabilitation.SignificanceOur findings highlight the importance of considering the physical effect of HMD wear in clinical testing, which may not be present with non-wearable VR technologies.     

Characteristics of older adults living with HIV accessing home and community care services in British Columbia,Canada

ABSTRACT

Over half of people living with HIV (PLHIV) engaged in care in British Columbia (BC) are age ≥50. The public home and community care (HCC) system offers formal support that PLHIV may turn to as they age, but little is known about access specific to PLHIV. Using data from the STOP HIV/AIDS cohort, which includes linked treatment and demographic records for PLHIV accessing care in BC, we compared older PLHIV (defined as those age ≥50) who did and did not access HCC services. We estimated adjusted odds ratios (aORs) for factors associated with HCC service utilization using logistic regression. This study included 5,603 PLHIV age ≥50, 837 (14.94%) of whom accessed any HCC service between 2005 and 2015. Services most commonly used were community nursing (8.98%, n?=?503) and rehabilitation (7.73%, n?=?433). Those who received HCC were more likely to be female (aOR?=?1.56, 95% CI?=?1.24, 1.98), have a history of injection drug use (aOR?=?1.88, 95% CI?=?1.57, 2.25), have a higher Charlson comorbidity score (aOR?=?1.11, 95% CI:1.07, 1.15) and to have visited a general practitioner in the past year (aOR?=?2.17, 95% CI?=?1.77, 2.67). Approximately 15% of older PLHIV have accessed HCC, but the extent of potential unmet need for these services requires further research.     

White matter hyperintensities affect transcranial electrical stimulation in the aging brain

BackgroundWhite matter hyperintensities (WMH) are estimated to occur in greater than 63% of older adults over the age of 60 years. WMH identified in the T2-weighted FLAIR images can be combined with T1-weighted images to enhance individualized current flow models of older adults by accounting for the presence of WMH and its effects on delivered tES current in the aging brain.MethodsIndividualized head models were derived from T1-weighted images of 130 healthy older adults (mean = 71 years). Lesions segmented from FLAIR acquisition were added to individualized models. Current densities were computed in the brain and compared between models with and without lesions.Main resultsIntegrating WMH into the models resulted in an overall decrease (up to 7%) in median current densities in the brain outside lesion regions. Changes in current density and total lesion volume was positively correlated (R² = 0.31, p < 0.0001).ConclusionsIncorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.     

Two-minute walk tests demonstrate similar age-related gait differences as a six-minute walk test

BackgroundThe six-minute walk test (6MWT) is used within clinical and research settings to assess gait performance across a variety of conditions and populations. Commonly, the test is used to identify specific aspects of gait that affect functional mobility. With the advancement of new technologies such as wireless inertial sensors, it has become possible to collect reliable, sensitive, and objective measures of gait. While the 6MWT has been accepted and used for many years, a more concise, while still objective gait analysis would likely benefit clinicians, researchers and patients.Research QuestionDoes a concise 2-minute walk test (2MWT) provide similar information regarding gait performance and gait differences as the 6MWT in healthy young (YA) and older adults (OA)?MethodsA total of thirty-one participants (sixteen young adults and fifteen older adults) conducted a continuous 6MWT at their self-selected pace. All participants wore six wireless inertial sensors which were placed on each foot, at the lumbar, sternum, and on each wrist. Once completed the 6MWT data was spliced into three, distinct two-minute segments. Spliced data was analyzed and compared between groups and segments.ResultsResults demonstrate significant age-related differences in several gait metrics, primarily with older adults showing increased spatiotemporal variability. Additionally, no significant differences were observed between the three, two-minute segments and the continuous 6MWT, with the exception of total number of strides completed.SignificanceThese results demonstrate that the 2MWT may provide a preferable alternative to assessing gait performance by reducing confounds such as fatigue while maintaining sensitivity of measuring gait performance. These improvements may be particularly beneficial when studying populations of advanced age or with neurological disorder.