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1.
Front Immunol ; 15: 1360141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361938

RESUMO

Immunosenescence describes dysregulation of the immune system with ageing manifested in both the innate and adaptive immunity, including changes in T-cell checkpoint signaling. Through complex and nuanced process, T-cells lose excitatory signaling pathways and upregulate their inhibitory signaling, leading to ineffective immune responses that contribute to the formation of the ageing phenotype. Here we expand on the expression, function, and clinical potential of targeting the T-cell checkpoint signaling in age and highlight interventions offering the most benefits to older adults' health. Notably, modifications in vaccination such as with mTOR inhibitors show immediate clinical relevance and good tolerability. Other proposed treatments, including therapies with monoclonal antibodies fail to show clinical efficacy or tolerability needed for implementation at present. Although T-cell co-signaling fits a valuable niche for translational scientists to manage immunosenescence, future study would benefit from the inclusion of older adults with multiple long-term conditions and polypharmacy, ensuring better applicability to actual patients seen in clinical settings.


Assuntos
Relevância Clínica , Imunossenescência , Humanos , Idoso , Envelhecimento , Imunossenescência/fisiologia , Imunidade Adaptativa , Receptores de Antígenos de Linfócitos T , Linfócitos T
2.
Curr Opin Clin Nutr Metab Care ; 27(3): 244-251, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38386477

RESUMO

PURPOSE OF REVIEW: Sarcopenia increases in prevalence at older ages and may be exacerbated by poor diet. Whole foods rich in specific nutrients may be myoprotective and mitigate the risk of sarcopenia. Here we review recent evidence published from observational and intervention studies regarding myoprotective foods and explore their benefit for the prevention and/or treatment of sarcopenia in older adults. RECENT FINDINGS: We found limited new evidence for the role of whole foods in sarcopenia and sarcopenia components (muscle mass, strength, physical performance). There was some evidence for higher consumption of protein-rich foods (milk and dairy) being beneficial for muscle strength in observational and intervention studies. Higher consumption of antioxidant-rich foods (fruit and vegetables) was associated with better physical performance and lower odds of sarcopenia in observational studies. Evidence for other protein- and antioxidant-rich foods were inconsistent or lacking. There remains a clear need for intervention studies designed to identify the role of whole foods for the treatment of sarcopenia. SUMMARY: Although evidence for myoprotective roles of dairy, fruit and vegetables is emerging from observational studies, higher level evidence from intervention studies is needed for these foods to be recommended in diets of older adults to prevent and/or treat sarcopenia.


Assuntos
Sarcopenia , Humanos , Idoso , Sarcopenia/prevenção & controle , Envelhecimento/fisiologia , Antioxidantes/uso terapêutico , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Verduras
3.
Geroscience ; 46(1): 1141-1158, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37434081

RESUMO

Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47-84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = - 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = - 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.


Assuntos
Proteína HMGB1 , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Lamina Tipo B , Estudos de Viabilidade , Músculo Esquelético , Senescência Celular , Fibrose
4.
J Frailty Sarcopenia Falls ; 8(4): 230-239, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046442

RESUMO

Older adults living with the complexity of multiple long-term conditions (MLTC), frailty and a recent deterioration in health are under-served by research. As a result, current treatment guidelines are often based on data from studies of younger and less frail participants, and often single disease focused. The aims of this review were (i) to identify why older adults living with the complexity of MLTC, frailty and a recent deterioration in health are under-served by research and (ii) to identify strategies for increasing their recruitment and retention. Although a range of factors have been suggested to affect the participation of older adults with MLTC and frailty in research, this review shows that much less is known about the inclusion of older adults living with the complexity of MLTC, frailty and a recent deterioration in health. Researchers should focus on strategies that minimise participation burden for these patients, maintaining an adaptive and flexible approach, to increase their recruitment and retention. Future research should include qualitative interviews to provide further insights into how best to design and conduct research to suit the needs of this population group.

5.
BMC Geriatr ; 23(1): 772, 2023 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001414

RESUMO

BACKGROUND: Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. METHODS: Fourteen participants aged 69-92 years (10 women) from the Lifestyle in Later Life - Older People's Medicine (LiLL-OPM) study were recruited from an Older People's Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. RESULTS: The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. CONCLUSIONS: Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.


Assuntos
Fragilidade , Treinamento Resistido , Humanos , Feminino , Idoso , Fragilidade/diagnóstico , Fragilidade/terapia , Exercício Físico , Terapia por Exercício , Estilo de Vida
6.
Clin Sci (Lond) ; 137(22): 1721-1751, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37986616

RESUMO

Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women. Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.


Assuntos
Sarcopenia , Masculino , Humanos , Feminino , Idoso , Sarcopenia/patologia , Envelhecimento/patologia , Senescência Celular/genética , Músculo Esquelético/patologia , Comunicação Celular
7.
Am J Clin Nutr ; 118(5): 852-864, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37657521

RESUMO

Sarcopenia is a common skeletal muscle disorder characterized by a loss of muscle mass and impaired muscle function that is associated with poor health outcomes. Although nutrition is considered an important factor in the etiology of sarcopenia, the preventive potential of diet, specifically the extent to which differences in habitual patterns of diet and/or nutrient intakes impact risk of its development, is poorly understood. This narrative review considered research evidence on dietary patterns and nutrient intakes in mid- (<60 y) and young-older (60-70 y) adulthood to evaluate how they relate to age-related changes in muscle mass and function. A key finding was that current evidence on adult diet and sarcopenia risk in older age is limited and fragmented, with different outcomes reported across studies (for example, lean mass, strength) and few reporting links to incident diagnosed sarcopenia. As these outcomes are not interchangeable, it challenges collation of the evidence, leaving many gaps in understanding. There is also limited information about adult (<70 y) diet and few longitudinal studies with repeated dietary assessments to enable definition of cumulative exposures across adulthood. However, despite these limitations, findings from studies of dietary patterns already provide reasonably consistent messages about the benefits of diets of higher quality in earlier adulthood for later physical performance, although whole-diet intervention trials are urgently needed to understand their potential. In comparison, there is little evidence of benefits of higher intakes of individual nutrients in earlier adulthood for later muscle mass and function. Although these gaps need to be addressed in future research, there may already be sufficient data to promote messages about diet quality more widely - that healthier diets of higher quality across adulthood, with known benefits for a range of health outcomes, are also linked to the effective preservation of muscle mass and function.


Assuntos
Sarcopenia , Adulto , Humanos , Força Muscular , Músculo Esquelético/fisiologia , Estado Nutricional , Dieta
8.
Neurol Sci ; 44(12): 4205-4217, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37594550

RESUMO

BACKGROUND: The prevalence of sarcopenia (reduced skeletal muscle strength and mass), Parkinson's disease (PD) and Parkinson's related disorders (PRD) all increase with age. They also share risk factors and pathogenetic features. An increased prevalence of sarcopenia in PD and PRD than the general population was thus postulated. METHODS: Four databases were searched using predefined literature search strategies. Studies conducted in participants with PD or PRD reporting the prevalence of sarcopenia and those providing data to compute the prevalence were included. Pre-sarcopenia, probable/possible sarcopenia and confirmed sarcopenia were defined according to the main sarcopenia working groups. Risk of bias was assessed using the AXIS tool. RESULTS: 1978 studies were identified; 97 assessed in full; 14 met inclusion criteria. The median study quality score was 15/20. The range of probable sarcopenia was 23.9 to 66.7%, and it did not change after excluding PRD participants. The prevalence of confirmed sarcopenia in participants with any parkinsonian disorder ranged from 2 to 31.4%. Including just PD participants, the range was 10.9 to 31.4%. In studies with controls, sarcopenia was more prevalent in PD and PRD. There was a positive non-significant trend between severity of motor symptoms and prevalence of sarcopenia or components of sarcopenia. High heterogeneity precluded meta-analysis, therefore there was insufficient evidence to conclude whether sarcopenia is more prevalent in PD or PRD. CONCLUSIONS: Probable and confirmed sarcopenia are common in PD and PRD and they may be associated with disease severity. This co-occurrence supports the value of screening for sarcopenia in parkinsonian populations.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Sarcopenia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Prevalência , Transtornos Parkinsonianos/complicações , Fatores de Risco
9.
Sports Med Open ; 9(1): 51, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37395837

RESUMO

BACKGROUND: Resistance exercise is recommended for maintaining muscle mass and strength in older adults. However, little is known about exercise-induced muscle damage and recovery from resistance exercise in older adults. This may have implications for exercise prescription. This scoping review aimed to identify and provide a broad overview of the available literature, examine how this research has been conducted, and identify current knowledge gaps relating to exercise-induced muscle damage and recovery from resistance exercise in older adults. METHODS: Studies were included if they included older adults aged 65 years and over, and reported any markers of exercise-induced muscle damage after performing a bout of resistance exercise. The following electronic databases were searched using a combination of MeSH terms and free text: MEDLINE, Scopus, Embase, SPORTDiscus and Web of Science. Additionally, reference lists of identified articles were screened for eligible studies. Data were extracted from eligible studies using a standardised form. Studies were collated and are reported by emergent theme or outcomes. RESULTS: A total of 10,976 possible articles were identified and 27 original research articles were included. Findings are reported by theme; sex differences in recovery from resistance exercise, symptoms of exercise-induced muscle damage, and biological markers of muscle damage. CONCLUSIONS: Despite the volume of available data, there is considerable variability in study protocols and inconsistency in findings reported. Across all measures of exercise-induced muscle damage, data in women are lacking when compared to males, and rectifying this discrepancy should be a focus of future studies. Current available data make it challenging to provide clear recommendations to those prescribing resistance exercise for older people.

10.
Age Ageing ; 52(7)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37466640

RESUMO

Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state-the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.


Assuntos
Senescência Celular , Senoterapia , Animais , Humanos , Senescência Celular/fisiologia , Envelhecimento/fisiologia , Longevidade , Inflamação
11.
Drugs Aging ; 40(8): 703-719, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37486575

RESUMO

Sarcopenia, the age-related loss of muscle strength and mass or quality, is a common condition with major adverse consequences. Although the pathophysiology is incompletely understood, there are common mechanisms between sarcopenia and the phenomenon of accelerated ageing seen in diabetes mellitus. Drugs currently used to treat type 2 diabetes mellitus may have mechanisms of action that are relevant to the prevention and treatment of sarcopenia, for those with type 2 diabetes and those without diabetes. This review summarises shared pathophysiology between sarcopenia and diabetes mellitus, including the effects of advanced glycation end products, mitochondrial dysfunction, chronic inflammation and changes to the insulin signalling pathway. Cellular and animal models have generated intriguing, albeit mixed, evidence that supports possible beneficial effects on skeletal muscle function for some classes of drugs used to treat diabetes, including metformin and SGLT2 inhibitors. Most human observational and intervention evidence for the effects of these drugs has been derived from populations with type 2 diabetes mellitus, and there is a need for intervention studies for older people with, and at risk of, sarcopenia to further investigate the balance of benefit and risk in these target populations. Not all diabetes treatments will be safe to use in those without diabetes because of variable side effects across classes. However, some agents [including glucagon-like peptide (GLP)-1 receptor agonists and SGLT2 inhibitors] have already demonstrated benefits in populations without diabetes, and it is these agents, along with metformin, that hold out the most promise for further investigation in sarcopenia.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Sarcopenia , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Humanos , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sarcopenia/tratamento farmacológico , Sarcopenia/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Reposicionamento de Medicamentos , Metformina/uso terapêutico , Hipoglicemiantes/efeitos adversos
12.
J Frailty Sarcopenia Falls ; 8(2): 127-135, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37275663

RESUMO

Community-dwelling older adults living with multiple long-term conditions (MLTC), frailty and a recent deterioration in health are underserved by research. This results in a limited evidence base for their care, including the potential benefits of lifestyle interventions such as structured exercise. The aims of the LiLL-OPM (Lifestyle in Later Life - Older People's Medicine) study are to determine if it is feasible to carry out a research project with these patients, describe their health and lifestyle, their attitudes to engaging in exercise and their experiences of taking part in the research. Older adults who are attending an Older People's Medicine Day Unit service in Newcastle, UK, and their informal carers will be invited to take part. The study will use mixed methods with semi-structured interviews and a health and lifestyle questionnaire, carried out in a way that is most convenient to participants, including in their own homes and with a flexible schedule of study visits. The findings from the feasibility study will provide invaluable data on how to design research, including the most suitable approaches to recruitment and data collection. This will improve the inclusion in research of older adults living with MLTC, frailty and a recent deterioration in health.

13.
Br J Nutr ; 129(5): 820-831, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35795912

RESUMO

Milk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the Medical Research Council National Survey of Health and Development to test sex-specific associations between milk consumption from age 36 to 60-64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-d food diaries (aged 36, 43, 53 and 60-64 years), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/d). GS was assessed at ages 53, 60-64, and 69 years, and probable sarcopenia classified at the age of 69 years. We employed logistic regression to examine the odds of probable sarcopenia and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58·76-145·25 g/d) of reduced-fat milk was associated with lower odds of sex-specific low GS at the age of 69 years (OR (95 % CI): 0·59 (0·37, 0·94), P = 0·03). In multilevel models, only T3 of total milk (≥ 237·52 g/d) was associated with stronger GS in midlife in men (ß (95 % CI) = 1·82 (0·18, 3·45) kg, P = 0·03) compared with T1 (≤ 152·0 g/d), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination.


Assuntos
Sarcopenia , Masculino , Humanos , Feminino , Adulto , Animais , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Leite , Força Muscular/fisiologia , Força da Mão/fisiologia , Músculo Esquelético/fisiologia
14.
Mech Ageing Dev ; 209: 111744, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368549

RESUMO

BACKGROUND: Advanced glycation end products (AGEs) and AGEs receptor (RAGE) may play a role in sarcopenia. This systematic review evaluated the associations between AGEs measured in tissues (skin) by autofluorescence (SAF) and/or circulation (blood, urine) and muscle health outcomes (strength, mass, function) and sarcopenia in observational studies. METHODS: MEDLINE, Embase, Scopus and Web of Science were searched for studies reporting associations between AGEs and muscle-related outcomes in community-dwelling adults aged ≥ 30 years (until March 2022). RESULTS: Fourteen cross-sectional and one prospective study were included in the narrative summary. SAF was negatively associated with muscle strength, mass, and physical functioning in adults aged ≥ 30 years (four studies), and muscle mass (three studies), strength, and sarcopenia (one study) in adults aged ≥ 65 years. Circulating AGEs were negatively associated with muscle strength and physical functioning (four studies) and predicted the risk of walking disability (one prospective study), and sarcopenia (one study) in older adults. The role of RAGE in muscle health was inconclusive. CONCLUSIONS: SAF and circulating AGEs were negatively associated with muscle-related outcomes in adults aged ≥ 30 years in cross-sectional studies. This finding should be confirmed in well-designed prospective studies investigating sarcopenia, as AGEs represent a potentially modifiable target for intervention.


Assuntos
Sarcopenia , Humanos , Idoso , Estudos Prospectivos , Estudos Transversais , Produtos Finais de Glicação Avançada , Músculo Esquelético
15.
J Intern Med ; 293(1): 100-109, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36131375

RESUMO

BACKGROUND: Numerous approaches are used to characterise multiple long-term conditions (MLTC), including counts and indices. Few studies have compared approaches within the same dataset. We aimed to characterise MLTC using simple approaches, and compare their prevalence estimates of MLTC and associations with emergency hospital admission in the UK Biobank. METHODS: We used baseline data from 495,465 participants (age 38-73 years) to characterise MLTC using four approaches: Charlson index (CI), Byles index (BI), count of 43 conditions (CC) and count of body systems affected (BC). We defined MLTC as more than two conditions using CI, BI and CC, and more than two body systems using BC. We categorised scores (incorporating weightings for the indices) from each approach as 0, 1, 2 and 3+. We used linked hospital episode statistics and performed survival analyses to test associations with an endpoint of emergency hospital admission or death over 5 years. RESULTS: The prevalence of MLTC was 44% (BC), 33% (CC), 6% (BI) and 2% (CI). Higher scores using all approaches were associated with greater outcome rates independent of sex and age group. For example, using CC, compared with score 0, score 2 had 1.95 (95% CI: 1.91, 1.99) and a score of 3+ had 3.12 (95% CI: 3.06, 3.18) times greater outcome rates. The discriminant value of all approaches was modest (C-statistics 0.60-0.63). CONCLUSIONS: The counts classified a greater proportion as having MLTC than the indices, highlighting that prevalence estimates of MLTC vary depending on the approach. All approaches had strong statistical associations with emergency hospital admission but a modest ability to identify individuals at risk.


Assuntos
Bancos de Espécimes Biológicos , Multimorbidade , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Hospitais , Reino Unido/epidemiologia
16.
Mech Ageing Dev ; 208: 111739, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36152894

RESUMO

Immunosenescence, a decline in immune system function, has been linked to several age-related diseases and ageing syndromes. Very old adults (aged ≥ 85 years) live with multiple long-term conditions (MLTC, also known as multimorbidity)-a complex phenomenon of poor health defined by either counts, indices, or patterns, but little is known about the relationship between an ageing immune system and MLTC in this age group. We utilised baseline data from the Newcastle 85+ Study to investigate the associations between previously defined immunosenescence profiles of lymphocyte compartments and MLTC counts and patterns (from 16 chronic diseases/ageing syndromes). Seven hundred and three participants had MLTC and complete data for all 16 conditions, a median and mean of 5 (range 2-11) and 62.2% had ≥ 5 conditions. Three distinct MLTC patterns emerged by clustering: Cluster 1 ('Low frequency cardiometabolic-cerebrovascular diseases', n = 209), Cluster 2 ('High ageing syndromes-arthritis', n = 240), and Cluster 3 ('Hypertensive-renal impairment', n = 254). Although having a more senescent phenotype, characterised by higher frequency of CD4 and CD8 senescence-like effector memory cells and lower CD4/CD8 ratio, was not associated with MLTC compared with less senescent phenotype, the results warrant further investigation, including whether immunosenescence drives change in MLTC and influences MLTC severity in late adulthood.


Assuntos
Imunossenescência , Multimorbidade , Linfócitos , Sistema Imunitário
17.
Nat Aging ; 2(7): 601-615, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36147777

RESUMO

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.


Assuntos
Envelhecimento , Senescência Celular , Humanos , Camundongos , Animais , Envelhecimento/genética , Senescência Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Fenótipo , Músculo Esquelético
18.
BMJ Open Sport Exerc Med ; 8(1): e001229, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35136657

RESUMO

INTRODUCTION: Resistance exercise has been shown to improve muscle health in older adults and is recommended as a front-line treatment for many health conditions, including sarcopenia and frailty. However, despite considerable research detailing the potential benefits of resistance exercise programmes, little is known about how older adults recover from individual exercise sessions. This scoping review will examine the current evidence surrounding the acute post-exercise effects of resistance exercise and the exercise recovery process in older adults to inform future research and exercise prescription guidelines for older adults. METHODS AND ANALYSIS: The methodological framework of Arksey and O'Malley (2005) will be applied for this scoping review. A systematic search of five online databases and the hand-searching of reference lists of identified articles will be used to identify relevant papers. Studies that aim to measure exercise-induced muscle damage or exercise recovery following a resistance exercise session in participants aged 65 years and over will be included. Qualitative and quantitative data from relevant studies will be presented in a tabular format. Results will be summarised in narrative format. Key findings will be discussed concerning resistance exercise prescription in older adults. DISSEMINATION: This review will be used to direct further research surrounding the exercise recovery process from resistance exercise in older adults and will also aid in designing specific exercise prescription guidelines for an older population. Findings will be relevant to researchers, clinicians, health workers and policy-makers and disseminated through publications and presentations.

19.
Age Ageing ; 51(2)2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35150587

RESUMO

Sarcopenia is a generalised skeletal muscle disorder characterised by reduced muscle strength and mass and associated with a range of negative health outcomes. Currently, resistance exercise (RE) is recommended as the first-line treatment for counteracting the deleterious consequences of sarcopenia in older adults. However, whilst there is considerable evidence demonstrating that RE is an effective intervention for improving muscle strength and function in healthy older adults, much less is known about its benefits in older people living with sarcopenia. Furthermore, evidence for its optimal prescription and delivery is very limited and any potential benefits of RE are unlikely to be realised in the absence of an appropriate exercise dose. We provide a summary of the underlying principles of effective RE prescription (specificity, overload and progression) and discuss the main variables (training frequency, exercise selection, exercise intensity, exercise volume and rest periods) that can be manipulated when designing RE programmes. Following this, we propose that an RE programme that consists of two exercise sessions per week and involves a combination of upper- and lower-body exercises performed with a relatively high degree of effort for 1-3 sets of 6-12 repetitions is appropriate as a treatment for sarcopenia. The principles of RE prescription outlined here and the proposed RE programme presented in this paper provide a useful resource for clinicians and exercise practitioners treating older adults with sarcopenia and will also be of value to researchers for standardising approaches to RE interventions in future sarcopenia studies.


Assuntos
Treinamento Resistido , Sarcopenia , Idoso , Humanos , Força Muscular/fisiologia , Músculo Esquelético , Prescrições , Sarcopenia/terapia
20.
Front Nutr ; 8: 748882, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671632

RESUMO

Resistance exercise is a widely advocated treatment for improving muscle strength and performance in older adults. Maximizing the benefit of resistance exercise by ensuring optimal recovery is an important aim and studies are now seeking interventions to expedite exercise recovery in older people. A recovery strategy that has acquired considerable interest is the consumption of protein, and more recently, the consumption of protein-rich whole foods. This study aimed to understand the perspectives of community-dwelling older adults, and determine their knowledge of exercise recovery strategies, their preferences for recovery strategies, and their attitudes toward using whole foods, such as milk as a post-exercise recovery aid. Two hundred ninety-one older adults (74 ± 4 years) were recruited to complete a self-administered online survey. A mixed methods approach was used to gather in-depth data from the cohort. Participants were asked to complete a combination of free-text (open-ended) and multiple-choice questions. Content analysis was conducted on responses to open-ended questions through a systematic classification process of coding. The most common recovery strategies reported were heat treatment, rest, and massage. Nutrition was rarely cited as a recovery strategy. Less than 2% of respondents mentioned nutrition, of these, only half mentioned a protein source. Forty-nine percent expressed negative opinions toward recovery supplements (e.g., "waste of money") compared to 7% expressing positive opinions. Whole foods such as milk, meat, fish, and fruit, were deemed to be a more acceptable recovery strategy than supplements by 80% of respondents. Those that found whole foods to be equally as acceptable (18%), cited efficacy as their main concern, and those that declared whole foods less acceptable (2%) had no common reason. Despite the high acceptability of whole foods, only 35% were aware that these foods could aid recovery. When asked about milk specifically, the majority of older adults (73%) said this would, or might, be an acceptable exercise recovery strategy. Those that found milk an unacceptable recovery strategy (27%) often cited disliking milk or an allergy/intolerance. In conclusion, whilst whole foods represented an acceptable recovery intervention for older adults, the majority were unaware of the potential benefits of nutrition for post-exercise recovery.

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