Preliminary evidence of differential expression of myogenic and stress factors in skeletal muscle of older adults with low muscle strength

Author(s):  
Sebastiaan Dalle ◽  
Jolan Dupont ◽  
Lenore Dedeyne ◽  
Sabine Verschueren ◽  
Jos Tournoy ◽  
...  

Abstract The age-related loss of muscle strength and mass, or sarcopenia, is a growing concern in the ageing population. Yet, it is not fully understood which molecular mechanisms underlie sarcopenia. Therefore, the present study compared the protein expression profile, such as catabolic, oxidative, stress-related and myogenic pathways, between older adults with preserved (8 ♀ and 5 ♂; 71.5 ±2.6 years) and low muscle strength (6 ♀ and 5 ♂; 78.0±5.0 years). Low muscle strength was defined as chair stand test time >15 seconds and/or handgrip strength <16kg (women) or <27kg (men) according the EWGSOP2 criteria. Catabolic signaling (i.e. FOXO1/3a, MuRF1, MAFbx, LC3b, Atg5, p62) was not differentially expressed between both groups, whereas the mitochondrial marker COX-IV, but not PGC1α and citrate synthase, was lower in the low muscle strength group. Stress factors CHOP and p-ERK1/2 were higher (~1.5-fold) in older adults with low muscle strength. Surprisingly, the inflammatory marker p-p65NF-κB was ~7-fold higher in older adults with preserved muscle strength. Finally, expression of myogenic factors (i.e. Pax7, MyoD, desmin; ~2-fold) was higher in adults with low muscle strength. To conclude, whereas the increased stress factors might reflect the age-related deterioration of tissue homeostasis, e.g. due to misfolded proteins (CHOP), upregulation of myogenic markers in the low strength group might be an attempt to compensate for the gradual loss in muscle quantity and quality. These data might provide valuable insights in the processes that underlie sarcopenia.

Author(s):  
Niccolo’ Tesi ◽  
Sven J van der Lee ◽  
Marc Hulsman ◽  
Iris E Jansen ◽  
Najada Stringa ◽  
...  

Abstract Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with maintained cognitive health (N = 343), a population-matched cohort of older adults from 5 cohorts (N = 2905), and summary statistics data from genome-wide association studies on parental longevity, we constructed a PRS including 330 variants that significantly discriminated between centenarians and older adults. This PRS was also associated with longer survival in an independent sample of younger individuals (p = .02), leading up to a 4-year difference in survival based on common genetic factors only. We show that this PRS was, in part, able to compensate for the deleterious effect of the APOE-ε4 allele. Using an integrative framework, we annotated the 330 variants included in this PRS by the genes they associate with. We find that they are enriched with genes associated with cellular differentiation, developmental processes, and cellular response to stress. Together, our results indicate that an extended human life span is, in part, the result of a constellation of variants each exerting small advantageous effects on aging-related biological mechanisms that maintain overall health and decrease the risk of age-related diseases.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-141
Author(s):  
Joseph Gordon III ◽  
Nicholas Remillard ◽  
Chad Straight ◽  
Rajakumar Nagarajan ◽  
Bruce Damon ◽  
...  

Abstract Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p<0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p<0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Amira Mohammed Ali ◽  
Hiroshi Kunugi

Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Given that social isolation is adopted as the most protective measure against COVID-19, the level of physical activity and the intake of adequate diet have considerably declined, especially among older adults—denoting an increased possibility for developing sarcopenia. Research also shows a higher vulnerability of sarcopenic people to COVID-19 as well as the development of wasting disorders such as sarcopenia and cachexia in a considerable proportion of symptomatic and recovering COVID-19 patients. Muscular wasting in COVID-19 is associated with poor prognosis. Accordingly, early detection and proper management of sarcopenia and wasting conditions in older adults and COVID-19 patients may minimize morbidity and mortality during the current COVID-19 crisis. This review explored different aspects of screening for sarcopenia, stressing their relevance to the detection of altered muscular structure and performance in patients with COVID-19. Current guidelines recommend prior evaluation of muscle strength by simple measures such as grip strength to identify individuals with proven weakness who then would be screened for muscle mass loss. The latter is best measured by MRI and CT. However, due to the high cost and radiation risk entailed by these techniques, other simpler and cheaper techniques such as DXA and ultrasound are given preference. Muscle loss in COVID-19 patients was measured during the acute phase by CT scanning of the pectoralis muscle simultaneously during a routine check for lung fibrosis, which seems to be an efficient evaluation of sarcopenia among those patients with no additional cost. In recovering patients, muscle strength and physical performance have been evaluated by electromyography and traditional tests such as the six-minute walk test. Effective preventive and therapeutic interventions are necessary in order to prevent muscle loss and associated physical decline in COVID-19 patients.


2020 ◽  
Vol 21 (2) ◽  
pp. 89-107
Author(s):  
Reona Chiba ◽  
Yuki Ohashi ◽  
Akiko Ozaki

Purpose Several epidemiological studies have reported an age-related increase in the prevalence of sleep disturbances. This study aims to investigate the relationship between sleep and sarcopenia/frailty in older adults and clarify issues that remain to be addressed in future studies. Design/methodology/approach PubMed was searched for relevant studies with the following keywords in the title: “sleep” and “sarcopenia” or “sleep” and “frailty.” A total of 15 studies published in English between 1998 and 2018 were reviewed. Findings Among the four studies that examined the relationship between sarcopenia and sleep, two reported that long or short sleep duration increased the risk of sarcopenia and this association was more pronounced in women than men. Among the seven studies examining the relationship between frailty and sleep, four reported that higher Pittsburgh Sleep Quality Index (PSQI) scores were associated with an increased risk of frailty. Practical implications Most previous studies have focused on interventions targeting a single area such as muscle strength or exercise habits, in older adults at risk for frailty. The results suggest that interventions targeting improved sleep may positively impact the maintenance of muscle strength. Originality/value The literature review revealed that too much or too little sleep increases the risk of sarcopenia in older adults. Further, sleep deprivation, greater night-time wakefulness and reduced sleep quality increase the risk of frailty. Interestingly, the risk of mortality is increased in individuals with daytime functional disorders such as excessive drowsiness or napping habits.


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027728 ◽  
Author(s):  
Siobhan Leahy ◽  
Marica Cassarino ◽  
Matthew DL O' Connell ◽  
Liam Glynn ◽  
Rose Galvin

IntroductionTwo major global health challenges are the rapidly ageing population and the high prevalence of obesity in all age groups. Older adults are also susceptible to age-related loss of muscle strength, termed dynapaenia. The co-occurrence of both obesity and dynapaenia, termed dynapaenic obesity (DO), has been associated with poorer health outcomes and increased healthcare usage compared with either state alone. The purpose of this systematic review is to quantify the prevalence and incidence of DO in older adult populations, and to explore the association between DO and health outcomes, specifically chronic disease and multimorbidity, functional disability and healthcare usage.Methods and analysisUsing the Meta-analyses Of Observational Studies in Epidemiology guidelines, we will conduct a systematic review of cross-sectional and longitudinal observational studies of older adults, which include measures of DO and specified outcomes. Detailed literature searches of will be conducted using six electronic databases: Excerpta Medica dataBASE (EMBASE), PubMed, MEDLINE, SCOPUS, ScienceDirect and Cumulative Index of Nursing and Allied Health Complete (CINAHL), including articles published from database inception until Febuary 2019. The reference lists of included articles will also be searched. Two independent reviewers will undertake a three-step screening and review process using the Population, Risk Factor, Outcome framework to define eligibility. The Newcastle Ottawa Scale for non-randomised studies will be used to assess risk of bias and to rate study quality. The findings will be synthesised in a narrative summary, and a meta-analysis will be conducted where appropriate.Ethics and disseminationEthical approval is not required for this systematic review. Findings from this research will be submitted for peer-reviewed publication in academic journals, and presented at relevant academic conferences.PROSPERO registration numberCRD42018112471.


2021 ◽  
Author(s):  
Alexander Capraro ◽  
Sharon L Wong ◽  
Anurag Adhikari ◽  
Katelin M Allan ◽  
Hardip R Patel ◽  
...  

AbstractAge-dependent differences in the clinical response to SARS-CoV-2 infection is well-documented1–3 however the underlying molecular mechanisms involved are poorly understood. We infected fully differentiated human nasal epithelium cultures derived from healthy children (1-12 years old), young adults (26-34 years old) and older adults (56-62 years old) with SARS-COV-2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host defence response. We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic drug targets. Viral load was lowest in infected older adult cultures despite the highest expression of SARS-CoV-2 entry and detection factors. We showed this was likely due to lower expression of hijacked host machinery essential for viral replication. Unlike the nasal epithelium of young adults and children, global host response and induction of the interferon signalling was profoundly impaired in older adults, which preferentially expressed proinflammatory cytokines mirroring the “cytokine storm” seen in severe COVID-194,5. In silico screening of our virus-host-drug network identified drug classes with higher efficacy in older adults. Collectively, our data suggests that cellular alterations that occur during ageing impact the ability for the host nasal epithelium to respond to SARS-CoV-2 infection which could guide future therapeutic strategies.


GeroScience ◽  
2021 ◽  
Author(s):  
Andrea Ágnes Molnár ◽  
György László Nádasy ◽  
Gabriella Dörnyei ◽  
Bernadett Bettina Patai ◽  
Jordan Delfavero ◽  
...  

Abstract Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.


BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e033096 ◽  
Author(s):  
Irena Papadopoulos ◽  
Christina Koulouglioti ◽  
Runa Lazzarino ◽  
Sheila Ali

ObjectivesSocially assistive humanoid robots are considered a promising technology to tackle the challenges in health and social care posed by the growth of the ageing population. The purpose of our study was to explore the current evidence on barriers and enablers for the implementation of humanoid robots in health and social care.DesignSystematic review of studies entailing hands-on interactions with a humanoid robot.SettingFrom April 2018 to June 2018, databases were searched using a combination of the same search terms for articles published during the last decade. Data collection was conducted by using theRayyansoftware, a standardised predefined grid, and a risk of bias and a quality assessment tool.ParticipantsPost-experimental data were collected and analysed for a total of 420 participants. Participants comprised: older adults (n=307) aged ≥60 years, with no or some degree of age-related cognitive impairment, residing either in residential care facilities or at their home; care home staff (n=106); and informal caregivers (n=7).Primary outcomesIdentification of enablers and barriers to the implementation of socially assistive humanoid robots in health and social care, and consequent insights and impact. Future developments to inform further research.ResultsTwelve studies met the eligibility criteria and were included. None of the selected studies had an experimental design; hence overall quality was low, with high risks of biases. Several studies had no comparator, no baseline, small samples, and self-reported measures only. Within this limited evidence base, the enablers found were enjoyment, usability, personalisation and familiarisation. Barriers were related to technical problems, to the robots’ limited capabilities and the negative preconceptions towards the use of robots in healthcare. Factors which produced mixed results were the robot’s human-like attributes, previous experience with technology and views of formal and informal carers.ConclusionsThe available evidence related to implementation factors of socially assistive humanoid robots for older adults is limited, mainly focusing on aspects at individual level, and exploring acceptance of this technology. Investigation of elements linked to the environment, organisation, societal and cultural milieu, policy and legal framework is necessary.PROSPERO registration numberCRD42018092866.


2021 ◽  
Vol 10 (23) ◽  
pp. 5552
Author(s):  
Silvia Giovannini ◽  
Fabrizio Brau ◽  
Raffaele Forino ◽  
Andrea Berti ◽  
Federica D’Ignazio ◽  
...  

Age-related muscle loss is a phenomenon that has been extensively studied in recent decades. Sarcopenia is a multisystem disease, which predisposes to muscle weakness and frailty. At around 50 years of age, an individual begins to lose muscle strength, although this becomes more evident after 70. Sarcopenia is a condition typically found in older adults but can also affect younger people. Sarcopenia is a preventable and treatable condition. In past years, methods and tools to recognize the condition early have been researched. For the development of therapeutic interventions, agreement on diagnosis is fundamental. In recent years, a possible role of ultrasonography in the diagnosis of sarcopenia has been evaluated, compared with the best-known techniques.


Author(s):  
Dennis E. Anderson ◽  
Michael L. Madigan

Significant age differences in self-selected gait kinetics have been reported in the literature. These include reduced torque and power at the ankle and increased work at the hip in older adults as compared to young adults [1, 2]. The reasons for these differences are complex and not fully understood. It is possible older adults adapt their gait to a safer, more stable gait pattern [3]. However, differences in gait may also be due to age-related neuromuscular changes such as reduced muscle strength in older adults [4].


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