Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function

Viña, José; Tarazona-Santabalbina, Francisco José; Pérez‐Ros, Pilar; Martínez-Arnau, Francisco Miguel; Borrás, Consuelo; Olaso‐González, Gloria; Salvador‐Pascual, Andrea; Gómez-Cabrera, Mari Carmen

doi:10.1016/j.mam.2016.04.005

Cited by 63 publications

(46 citation statements)

References 221 publications

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“…Our findings are consistent with the observation that frail patients are at increased risk of poor outcomes in other settings and after healthcare interventions [41, 42]. Potential causes for poor outcomes experienced by critically ill frail patients include its underlying pathophysiology of neuromuscular weakness, sarcopenia, decreased oxygen utilization, inflammation, and immunosenescence [9, 18, 43] reflecting a wide range of age-related molecular and cellular deficits [44, 45]. These may increase susceptibility to inflammatory insults and nosocomial infections common in critical illness.…”

Section: Discussionsupporting

confidence: 88%

“…For example, frail patients may be more difficult to wean from mechanical ventilation because of weakness, sarcopenia, and decreased oxygen uptake [9, 17, 18, 43]. Further, as a result of immunosenescence, frail patients may need more time to recover from infections including those nosocomially acquired [45]. Our results are not in keeping with data in surgical populations, which have demonstrated that frail patients have longer stays in hospital and recovery time [6].…”

Section: Discussionmentioning

confidence: 99%

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The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

et al. 2017

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PurposeFunctional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU.MethodsWe searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay.ResultsTen observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p < 0.00001; I 2 = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p < 0.00001; I 2 = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p < 0.00001; I 2 = 12%).ConclusionsFrailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-017-4867-0) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

et al. 2017

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“…Studies have suggested a genetic basis, with heritability estimates between 19 and 45% (Livshits, Lochlainn, et al 2018) (Murabito et al 2012) (Young et al 2016). Candidate gene association studies for frailty have suggested the involvement of genes in inflammatory pathways (Viña et al 2016), including tumour necrosis factor (Mekli et al 2016) and interleukin-18 (Mekli et al 2015). Large-scale GWAS are needed to better understand the genetic determinants of frailty and associated biological pathways.…”

Section: Introductionmentioning

confidence: 99%

A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Aging

Atkins

Jylhävä²,

Pedersen

et al. 2019

Preprint

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Frailty is a common geriatric syndrome, strongly associated with disability, mortality and hospitalisation. The mechanisms underlying frailty are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 19 and 45%. Understanding the genetic determinants and biological mechanisms underpinning frailty may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) of a frailty index (FI) in European descent participants from UK Biobank (n=164,610, aged 60-70 years). FI calculation was based on 49 self-reported items on symptoms, disabilities and diagnosed diseases. We identified 26 independent genetic signals at 24 loci associated with the FI (p<5*10-8). Many of these loci have previously been associated with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, three appear to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 14% (0.14, SE 0.006). A genetic risk score for the FI, derived solely from the UK Biobank data, was significantly associated with FI in the Swedish TwinGene study (n=10,616, beta: 0.11, 95% CI: 0.02-0.20, p=0.015). In pathway analysis, genes associated with synapse function were significantly enriched (p<3*10-6). We also used Mendelian randomization to identify modifiable traits and exposures that may affect the risk of frailty, with a higher educational attainment genetic risk score being associated with a lower risk of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on synapse maintenance pathways.

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“…Randomized controlled trials show that resistance exercise provides the best protection against sarcopenia [29,30]. A stronger body will also make it easier to perform daily activities [31], improve quality of life, potentially enabling older people to extent the period living at home, and spearing the society for a substantial amount of money [32]. Strength exercise programs should therefore be an important part of disease recovery for all, but especially for older people as they rapidly loose muscle mass when immobilized.…”

Section: Strength Exercise To Promote Muscle Growthmentioning

confidence: 99%

Fighting Inactivity to Improve Health: A Short Commentary

Gjevestad¹,

Ulven²,

Holven³

2017

Health Edu Care

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Physical inactivity has been identified as the fourth leading risk factor for global mortality, causing around 3.2 million deaths each year. It increases the risk of developing diseases such as cardiovascular diseases, cancers, diabetes type 2 and obesity. However, considerable improvements in public health may be possible even with a small increase in physical activity level across all age groups. Great efforts should therefore be made, both at governmental and individual level, to encourage people to walk the stairs instead of taking the elevator, walk or ride a bike instead of driving the car or take an afternoon walk instead of spending time in front of the television. In this short commentary, overall health benefits of regular physical activity will be briefly summarized. We will also touch upon physical training, including strength exercise, as tools to improve health outcomes, and the use of self-monitoring as a device to assess physical activity levels.

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Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function

Cited by 63 publications

References 221 publications

The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Aging

Fighting Inactivity to Improve Health: A Short Commentary

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