Sleep Disturbances and Sarcopenia in Older Adults: Clinical Associations, Potential Mechanisms, and Management Strategies

Abstract

Sarcopenia is an age-related syndrome characterized by reduced skeletal muscle mass, decreased muscle strength, and impaired physical performance, and is an important contributor to falls, disability, hospitalization, and mortality in older adults. Sleep disturbances, including abnormal sleep duration, poor sleep quality, insomnia, circadian disruption, and obstructive sleep apnea (OSA), are also highly prevalent in this population and may be associated with poorer physical performance. Accumulating observational evidence suggests an association between sleep disturbances and sarcopenia, although its directionality remains uncertain. This narrative review summarizes current clinical evidence linking sleep disturbances to sarcopenia in older adults, discusses potential biological and behavioral pathways underlying this relationship, and outlines clinically relevant management strategies. A particular focus is the comparison of evidence across sleep domains, sarcopenia components, and study designs, distinguishing clinically defined sarcopenia from individual muscle traits and biological plausibility from demonstrated mediation. Potential pathways involve circadian disruption, neuroendocrine and metabolic dysregulation, chronic inflammation, mitochondrial dysfunction and oxidative stress, although direct mechanistic evidence in older adults remains limited. Sleep assessment and management of clinically identified sleep disturbances may complement exercise and nutritional support, but their effects on sarcopenia outcomes remain uncertain. The available clinical evidence is predominantly observational and often cross-sectional; prospective studies and adequately powered randomized trials in older adults with both conditions are needed to clarify causality and treatment benefits.

Introduction

Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, decreased muscle strength, and impaired physical performance. According to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), low muscle strength is considered the primary parameter for identifying probable sarcopenia. The diagnosis of sarcopenia is confirmed when low muscle strength is accompanied by low muscle quantity or quality, whereas the additional presence of impaired physical performance indicates severe sarcopenia.¹ For Asian populations, the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria are widely used.² These criteria similarly define low muscle strength, low muscle mass, and impaired physical performance as the core diagnostic components, while providing population-specific cut-off values based on the anthropometric characteristics of Asian individuals. Differences in diagnostic criteria, assessment tools, and cut-off values may contribute to heterogeneity in reported prevalence and in associations between sleep-related factors and sarcopenia.

With the acceleration of global population aging, sarcopenia has become a major public health challenge because it contributes substantially to falls, frailty, disability, hospitalization, and increased all-cause mortality among older adults.^3,4 It has been reported that the prevalence of sarcopenia among individuals aged 60 years and older ranges from 10% to 16% worldwide,⁵ and this burden is particularly prominent in Asian populations.⁶

Meanwhile, sleep disturbances are highly prevalent among older adults.^7,8 In this review, the term “sleep disturbances” is used broadly to encompass unfavorable alterations in sleep duration, sleep quality, sleep timing, and circadian regularity, as well as insomnia symptoms and specific sleep disorders, including obstructive sleep apnea (OSA) and restless legs syndrome (RLS). These sleep-related domains may have distinct associations with muscle mass, muscle strength, and physical performance.

In recent years, growing epidemiological evidence suggests an association between sleep disturbances and sarcopenia.^9–12 Previous reviews have synthesized sleep duration and quality in relation to sarcopenia,^13,14 and a recent meta-analysis has examined the association of OSA with sarcopenia.¹⁵ Some earlier reviews also discuss hormonal, inflammatory and metabolic mechanisms and management implications.¹⁴ Important questions remain regarding how associations vary across sleep domains and sarcopenia components, the temporal direction of associations between sleep disturbances and sarcopenia, and whether interventions targeting sleep improve muscle outcomes. It is also unclear whether the proposed biological mechanisms mediate these associations in older adults.

Building on previous reviews, this narrative review compares evidence across multiple sleep domains, distinct sarcopenia components, and study designs. It differentiates clinically confirmed sarcopenia from possible or probable sarcopenia and individual measures of muscle mass, strength, and physical performance. It also distinguishes evidence supporting individual biological pathway components from evidence that these pathways mediate muscle decline associated with sleep disturbances, and separates demonstrated improvements in sleep from potential benefits for muscle health. Through these comparisons, the review integrates clinical associations, proposed mechanisms, and management implications, while clarifying the applicability of current evidence to older adults and the questions that require further investigation.

Methods

This narrative review was conducted to summarize current evidence regarding the association between sleep disturbances and sarcopenia in older adults. Relevant articles were identified through searches of PubMed, Web of Science, Embase, and Google Scholar conducted up to September 2026. Search terms included combinations of “sleep disturbances”, “sleep disorder”, “sleep duration”, “sleep quality”, “insomnia”, “obstructive sleep apnea”, “OSA”, “restless legs syndrome”, “RLS”, “circadian rhythm”, “sarcopenia”, “muscle mass”, “muscle strength”, “physical performance”, and “older adults”. Original studies, systematic reviews, meta-analyses, and clinical guidelines published in English were considered. Human studies involving older adults were prioritized when evaluating clinical associations and management implications. Studies in younger populations and preclinical models were included where relevant to potential mechanisms, with their limited applicability to older adults explicitly considered. Additional references were identified from the reference lists of relevant articles. As this was a narrative review, no formal risk-of-bias assessment or meta-analysis was performed.

Clinical Associations Between Sleep Disturbances and Sarcopenia

Sleep disturbances encompass unfavorable alterations in sleep duration, sleep quality, sleep timing and circadian regularity, as well as insomnia symptoms and specific sleep disorders. These domains may be differentially associated with sarcopenia and its components. Table 1 compares selected clinical and genetic studies, recording population characteristics, exposure assessment, outcome definitions, key estimates and limitations. Cross-sectional associations, longitudinal associations and Mendelian randomization (MR) findings address different questions and should not be interpreted as interchangeable evidence of causality.

Table 1.

Summary of Major Clinical Studies Examining Associations Between Sleep Disturbances and Sarcopenia-Related Outcomes

Sleep Domain/Study	Design and Population	Sleep Assessment/Exposure	Muscle Definition/Outcome	Main Findings	Interpretation and Limitations
Sleep duration Han P (2022).16	3-year prospective cohort; 754 Chinese adults aged ≥60 years	Interview-reported bedtime and rise time; short <6 h and long >8 h, each versus 6–8 h.	AWGS-defined sarcopenia: low muscle mass plus low strength and/or low performance	Adjusted ORs (95% CIs) for incident sarcopenia: short sleep 2.74 (1.05–7.13); long sleep 1.84 (1.07–3.14).	Supports temporality, not causality; wide CIs, self-reported sleep and residual confounding.
Sleep duration Peng X (2024).17	Cross-sectional CHARLS analysis; 7,342 older Chinese adults	Self-reported sleep duration; short ≤6 h and long ≥8 h, each versus 6–8 h.	AWGS 2019-based possible sarcopenia and sarcopenia; muscle mass estimated anthropometrically	Adjusted ORs (95% CIs) for possible sarcopenia: short sleep 1.30 (1.03–1.65), long sleep 1.33 (1.05–1.69); for sarcopenia, long sleep 1.41 (1.01–2.02).	Temporal direction cannot be determined; self-reported sleep; estimated muscle mass limits comparability with directly measured muscle outcomes.
Sleep duration Chen L (2024).18	4-year CHARLS follow-up; 5,654 middle-aged and older Chinese adults	Self-reported sleep duration; short ≤6 h and long >8 h, each versus 6–8 h.	AWGS 2019-based possible sarcopenia; low grip strength	Adjusted ORs (95% CIs) for short sleep: possible sarcopenia 1.18 (1.02–1.36); low grip strength 1.20 (1.02–1.41).	Possible rather than confirmed sarcopenia; mainly middle-aged participants; self-report and residual confounding.
Sleep duration Nakakubo S (2021).19	4-year cohort; 3,918 Japanese adults aged ≥65 years	Self-reported sleep duration; short ≤6 h and long ≥9 h, each versus 6.1–8.9 h.	EWGSOP2-based diagnostic sarcopenia; strength, bioimpedance muscle mass and gait speed	Adjusted ORs (95% CIs) for long sleep: progression to sarcopenia 1.66 (1.02–2.69); slow gait 1.55 (1.17–2.06); low grip strength 1.34 (1.00–1.78). No significant association was found with low muscle mass.	Long but not short sleep was associated with progression; component-specific findings and CIs do not support a uniform effect on muscle mass.
Sleep duration Wang Y (2025).20	CHARLS 2011–2020 cohort; 2,061 older Chinese adults; median follow-up 5 years	Baseline sarcopenia predicting subsequent self-reported sleep <6 h or >8 h	AWGS 2019-based sarcopenia/possible sarcopenia	Model 3 HRs (95% CIs) for sarcopenia versus nonsarcopenia: abnormal sleep 1.204 (1.023–1.417); long sleep 1.566 (1.192–2.057). Possible sarcopenia and long sleep: 1.286 (1.054–1.570).	Supports a reverse temporal association, not reciprocal causality; self-reported sleep
Sleep quality Cacciatore S (2025).21	Cross-sectional study; 1,971 community-dwelling older adults; mean age 73.4 years	Subjective sleep-quality item over the past month; bad versus good sleep	Probable sarcopenia: grip strength <27 kg in men or <16 kg in women	Fully adjusted OR (95% CI) for probable sarcopenia 1.40 (1.08–1.81).	Low strength alone, not confirmed sarcopenia; subjective sleep rating and cross-sectional design.
Sleep quality You Y (2023).22	Cross-sectional NHANES analysis; 5,143 adults aged 18–60 years	Self-reported trouble sleeping	Muscle quality index: handgrip strength relative to muscle mass	Higher muscle quality index was associated with lower odds of trouble sleeping.	Complementary adult evidence; not clinically diagnosed sarcopenia and limited direct applicability to older adults.
Sleep timing Choi YI (2019).23	Cross-sectional Korean population study; 9,105 workers	Self-reported work schedule; shift versus non-shift work	DXA muscle mass/BMI; threshold 1 SD below a young reference group	Fully adjusted Model 5 OR (95% CI) for sarcopenia in shift versus nonshift workers: 1.3 (1.1–1.5).	Occupational rather than geriatric population; muscle-mass-only definitions, not equivalent to confirmed sarcopenia under current criteria.
OSA Sun H (2025).24	Two-sample MR using large GWAS datasets; sample sizes vary by trait	OSA as the outcome, using GWAS summary data.	Genetically predicted sarcopenia-related traits: grip strength and walking pace	IVW OR (95% CI) for OSA risk associated with genetically predicted low grip strength: 1.190 (1.003–1.413; P=0.047). Left/right grip strength results were not significant; higher walking pace was inversely associated with OSA.	Estimates depend on instrument validity and pleiotropy assumptions. Does not establish effects of clinically diagnosed sarcopenia.
Insomnia Ye R (2024).11	Bidirectional two-sample MR using sleep- and muscle-trait GWAS datasets	Genetically predicted insomnia and other sleep traits	Bilateral grip strength, appendicular lean mass and walking pace	Genetically predicted insomnia was associated with lower bilateral grip strength and slower walking pace; reverse analyses suggested associations for some traits.	Individual traits, rather than clinically diagnosed sarcopenia; estimates depend on instrument validity and MR assumptions.
RLS Gokdeniz Yildirim A (2025).25	Cross-sectional geriatric clinic study; 109 patients with RLS and 220 controls	Turkish IRLSSG diagnostic assessment	EWGSOP2-based probable sarcopenia and sarcopenia; gait speed	Adjusted ORs (95% CIs) for RLS: probable sarcopenia 2.621 (1.265–5.431); sarcopenia 4.542 (1.284–16.071); slow gait 2.663 (1.432–4.951).	Small clinical sample and wide CIs; low-muscle-mass association was not significant after adjustment; temporal direction uncertain.

Abbreviations: AWGS, Asian Working Group for Sarcopenia; BMI, body mass index; CHARLS, China Health and Retirement Longitudinal Study; CI, confidence interval; DXA, dual-energy X-ray absorptiometry; EWGSOP2, European Working Group on Sarcopenia in Older People 2; GWAS, genome-wide association study; HR, hazard ratio; IRLSSG, International Restless Legs Syndrome Study Group; IVW, inverse-variance weighted; MR, Mendelian randomization; NHANES, National Health and Nutrition Examination Survey; OR, odds ratio; OSA, obstructive sleep apnea; RLS, restless legs syndrome; SD, standard deviation.

Sleep Duration

Previous observational studies have reported a U-shaped association between sleep duration and sarcopenia, although findings are not consistent across studies.^16,17,26 A 3-year prospective study of older Chinese adults found that both short and long sleep duration were associated with incident sarcopenia.¹⁶ However, cross-sectional findings varied by outcome definition and analytical approach, and cannot establish temporal relationships.^17,26 A 4-year follow-up study of middle-aged and older Chinese adults found that short sleep duration was associated with possible sarcopenia at follow-up after adjustment for measured confounders.¹⁸ This finding concerns possible rather than confirmed sarcopenia. Differences across studies may reflect population characteristics, diagnostic criteria, and sleep assessment methods. In contrast, a 4-year Japanese cohort study reported that long sleep duration (≥9 h/night), but not short sleep duration, was associated with progression to sarcopenia in older adults.¹⁹ Long sleep duration was also associated with low handgrip strength and slow gait, but not significantly with low muscle mass, suggesting that associations may differ across sarcopenia components. However, sleep duration was self-reported and therefore susceptible to recall bias. In older adults, prolonged time in bed, nocturnal awakenings, and reduced sleep efficiency may complicate the estimation of actual sleep duration. Long reported sleep duration may partly reflect chronic disease burden, frailty, depression, or poor sleep efficiency rather than an independent causal factor.

In addition, a Chinese cohort using CHARLS data from 2011–2020 found that baseline sarcopenia was associated with subsequent abnormal sleep duration (<6 h/night or >8 h/night; adjusted HR: 1.204, 95% CI: 1.023–1.417).²⁰ Sarcopenia and possible sarcopenia were also associated with subsequent long sleep duration. These findings support a possible reverse temporal association, although the underlying mechanisms were not established.

Overall, current evidence suggests that abnormal sleep duration and sarcopenia may be associated in both directions, but reciprocal causality remains unproven. Self-reported sleep assessments, heterogeneous outcome definitions, and residual confounding limit interpretation. Further longitudinal studies using objective sleep assessments are needed to clarify the temporal direction and clinical relevance of these associations.

Sleep Quality and Sleep Timing

In addition to sleep duration, sleep quality is associated with sarcopenia-related outcomes. A cross-sectional study of community-dwelling older adults found that 28.3% reported poor subjective sleep quality, which was associated with higher odds of probable sarcopenia, defined by low handgrip strength, after adjustment for measured confounders.²¹ Complementary evidence from a cross-sectional NHANES analysis of 5,143 adults aged 18–60 years showed that a higher muscle quality index, reflecting handgrip strength relative to muscle mass, was associated with lower odds of self-reported trouble sleeping.²² However, this study did not assess clinically defined sarcopenia, and its applicability to older adults is limited. Both studies relied on self-reported sleep assessments, and their cross-sectional designs preclude determination of temporal direction or causality. Sleep timing may also be relevant to muscle health. Cross-sectional studies in middle-aged adults and Korean workers reported that evening chronotype and circadian misalignment, such as shift work and habitual late bedtime, may be associated with impaired muscle function and sarcopenia-related outcomes.^23,27 Individuals with circadian rhythm disruption or evening chronotype may also be more likely to present with sarcopenic obesity characterized by low muscle mass and high body fat.²⁸ This may be related to behavioral and metabolic features such as nighttime eating, reduced daytime activity, increased social jetlag, fat accumulation, insulin resistance, and chronic inflammatory responses. Nevertheless, evidence linking sleep timing to sarcopenia specifically in older adults remains limited.

Obstructive Sleep Apnea (OSA)

Cross-sectional evidence links OSA with early-onset sarcopenia and sarcopenic obesity.²⁹ A meta-analysis of eight cross-sectional studies involving 13,331 participants reported higher odds of sarcopenia in adults with OSA (pooled OR 1.85, 95% CI 1.30–2.63; I²=62%).¹⁵ Associations varied by population and sleep assessment method. This pooled result supports a clinical association but cannot resolve temporality, and differences in OSA and sarcopenia definitions limit direct comparison across studies.

MR findings provide complementary, trait-specific evidence. Genetically predicted low grip strength in adults aged ≥60 years showed a nominal association with higher OSA risk, whereas separate left- and right-hand grip-strength analyses were not significant.²⁴ Usual walking pace was inversely associated with OSA. These results should be interpreted in the context of multiple tested traits and instrument assumptions, rather than as proof that clinically diagnosed sarcopenia causes OSA.

Intermittent hypoxia, sleep fragmentation and sympathetic activation may contribute to inflammation, oxidative stress and insulin resistance, but the supporting mechanistic evidence is derived mainly from experimental models and bioinformatic analyses.^30,31 Imaging studies have shown altered muscle quality and body composition in patients with OSA.³² Questionnaire-defined probable OSA has also been associated with reduced handgrip strength and impaired physical performance.³³ Among patients with chronic obstructive pulmonary disease complicated by OSA, handgrip strength and six-minute walking distance were further reduced, although the small sample size and cross-sectional design limit interpretation.³⁴

Insomnia

Current evidence suggests that insomnia may be primarily associated with reduced muscle strength and impaired physical performance. A bidirectional MR study found that insomnia was associated with lower bilateral handgrip strength and slower walking pace.¹¹ However, these findings also concern individual sarcopenia-related traits rather than clinically diagnosed sarcopenia and remain dependent on the assumptions of MR. In adults aged ≥80 years, the coexistence of insomnia and sarcopenia was associated with higher odds of cognitive impairment and limitations in activities of daily living.³⁵ Although a multiplicative interaction was observed for cognitive performance, the observational design does not establish that insomnia causally worsens functional impairment in individuals with sarcopenia.

Restless Legs Syndrome (RLS)

RLS is a sleep-related movement disorder characterized by unpleasant sensations and an urge to move the lower limbs during nighttime or at rest. It often leads to difficulty falling asleep, sleep fragmentation, and poor sleep quality. Compared with OSA and insomnia, studies on the association between RLS and sarcopenia are relatively limited. Existing cross-sectional evidence suggests that RLS may be associated with lower fat-free mass and reduced skeletal muscle mass, and this association appears to be more pronounced in men.³⁶ Some observational studies have reported that the prevalence of sarcopenia is higher among older adults with RLS and is accompanied by reduced muscle strength and slower gait speed.²⁵ These findings cannot establish temporal or causal relationships and require replication in larger longitudinal studies.

Potential Pathophysiological Mechanisms

Sleep disturbances and sarcopenia may be linked through multiple, interacting biological and behavioral pathways rather than through a single mechanism. Proposed pathways include circadian disruption, neuroendocrine and metabolic dysregulation, chronic inflammation, mitochondrial dysfunction and oxidative stress, gut microbiota dysbiosis, abnormal neural regulation, and behavioral factors such as physical inactivity and malnutrition. These mechanisms may affect muscle protein turnover, neuromuscular function, energy metabolism, and regenerative capacity. Conversely, sarcopenia may contribute to sleep disturbances through reduced physical activity, respiratory and upper-airway muscle weakness, metabolic dysfunction, and malnutrition, although evidence for these reverse pathways remains limited (Figure 1).

Figure 1.

Potential biological and behavioral mechanisms linking sleep disturbances and sarcopenia in older adults. Dashed arrows indicate potential pathways through which sarcopenia may contribute to sleep disturbances; these pathways remain incompletely established. Upward and downward arrows summarize proposed or reported changes across the cited studies and do not establish mediation in older adults with both conditions.

Abbreviations: HPA, hypothalamic-pituitary-adrenal; IL-6, interleukin-6; CRP, C-reactive protein; TNF-α, tumor necrosis factor-α; NF-κB, nuclear factor kappa B; SCFAs, short-chain fatty acids; BDNF, brain-derived neurotrophic factor; GABA, γ-aminobutyric acid.

The principal proposed mechanisms, together with their supporting evidence and major limitations, are summarized in Table 2. The table distinguishes findings from human observational studies, experimental studies, genetic analyses, and animal models, and separates evidence that sleep disturbances affect a given pathway from evidence that the pathway is associated with muscle loss or impaired muscle function. This distinction is important because evidence supporting individual components of a proposed pathway does not necessarily demonstrate a causal or mediating role in the development of sarcopenia.

Table 2.

Comparison of Evidence for Proposed Mechanisms Linking Sleep Disturbances with Sarcopenia

Proposed Mechanism	Sleep-Related Evidence	Muscle-Related Evidence	Evidence Interpretation and Key Limitations	Key References
Circadian rhythm disruption	Human sleep-deprivation experiments reported reduced peripheral blood expression of BMAL1 and CLOCK. Muscle-specific Bmal1 manipulation altered sleep amount and the response to sleep loss in mice.	CLOCK and BMAL1 regulate MyoD expression and skeletal muscle homeostasis. Muscle-specific Bmal1 restoration in knockout mice improved muscle strength and systemic health but did not restore muscle mass or fiber size.	Mechanistic support is derived mainly from genetic mouse models. Peripheral blood clock-gene expression does not directly reflect the circadian state of skeletal muscle. Clinical benefits of circadian interventions for sarcopenia remain unestablished.	[37–41]
Neuroendocrine and metabolic dysregulation	In healthy young adults, acute sleep deprivation can increase cortisol and decrease testosterone. Testosterone responses depend partly on which portion of the night is lost. Slow-wave sleep is closely associated with the major nocturnal growth hormone pulse.	In a randomized crossover study of 13 healthy young adults, one night of total sleep deprivation reduced muscle protein synthesis by 18% and increased cortisol by 21%, without significant changes in measured markers of muscle protein degradation.	Short-term human experiments show reduced muscle protein synthesis after sleep loss, accompanied by hormonal changes. They do not establish that these hormonal changes mediate the reduction in synthesis, persist with chronic sleep disturbance, or lead to sarcopenia in older adults.	[42–45]
Chronic inflammation	A meta-analysis of 35 experimental studies involving 887 participants found increased IL-6 and CRP after multiple nights of partial sleep deprivation, whereas a single night of sleep deprivation did not produce similar changes.	Observational studies in older adults have associated sarcopenia with higher inflammatory marker levels and impaired muscle function. Sustained inflammatory signaling may disrupt muscle protein turnover and regenerative capacity.	Human experimental evidence supports sleep-related inflammatory changes, but evidence linking inflammation to sarcopenia is largely observational. Whether inflammation mediates sleep-related muscle decline has not been established.	[46–50]
Mitochondrial dysfunction and oxidative stress	Five nights of sleep restriction impaired skeletal muscle mitochondrial respiratory function and sarcoplasmic protein synthesis in healthy young men; exercise attenuated these effects. Transcriptomic and animal studies provide complementary evidence of altered redox and mitochondrial responses.	Human studies of sarcopenia have reported impaired mitochondrial bioenergetics, reduced oxidative capacity, and altered NAD+ biosynthesis. Experimental studies implicate impaired mitochondrial dynamics, defective mitophagy, excessive mitochondrial reactive oxygen species, and reduced ATP availability in muscle atrophy.	Short-term human experiments demonstrate altered muscle mitochondrial function after sleep restriction. Animal studies report inconsistent oxidative-stress responses, including no detectable lipid or protein oxidative damage in some experiments. These findings do not establish that sleep-related mitochondrial or oxidative changes cause sarcopenia in older adults.	[51–57]
Gut microbiota dysbiosis	In healthy adults, shorter sleep has been associated with lower fecal human defensin 5, altered microbiota and lower fecal short-chain fatty acid levels. Preclinical studies summarized in the cited reviews suggest that sleep deprivation can disrupt intestinal barrier integrity and increase exposure to bacterial products; this is distinct from the human observational evidence.	Short-chain fatty acid supplementation improved muscle mass, muscle function, and mitochondrial biogenesis in sarcopenic mice through pathways involving AKT/mTOR and AMPK/PGC-1α signaling. Mendelian randomization analyses suggest associations between genetically predicted gut microbiota or metabolites and sarcopenia-related traits.	The evidence combines human observational studies, animal intervention studies, and genetic inference. Mendelian randomization findings depend on instrumental-variable assumptions and do not establish a sleep–microbiota–muscle pathway. Direct evidence in older humans remains limited.	[58–62]
Proposed Mechanism	Sleep-Related Evidence	Muscle-Related Evidence	Evidence Interpretation and Key Limitations	Key References
Irisin/BDNF signaling	Cortical BDNF manipulation altered subsequent NREM slow-wave activity in rats. FNDC5 manipulation altered neuronal or hippocampal BDNF expression in experimental models. Circulating irisin has been associated with the presence and severity of obstructive sleep apnea in human studies.	Lower circulating irisin levels have been associated with presarcopenia or sarcopenia.	The available evidence supports separate components of a proposed muscle–brain pathway. It has not been demonstrated that muscle-derived irisin regulates sleep through central BDNF or that this pathway mediates the relationship between sleep disturbances and sarcopenia in older adults.	[63–66]
GABAergic signaling	GABAergic neurons in the preoptic hypothalamus promote sleep by inhibiting wake-promoting neuronal populations. Experimental sleep deprivation alters hippocampal GABA receptor expression and synaptic plasticity.	GABA administration improved muscle mass and strength in aged female mice and was associated with changes in Akt/mTOR-, FoxO3a-, atrophy-related, and inflammatory signaling. Separate experimental work reported GABA-induced irisin release from skeletal muscle.	Evidence is predominantly preclinical. Effects of administered GABA on muscle do not establish a role for central sleep-regulating GABA circuits. The cited studies do not show that muscle benefits are mediated by improved sleep, or that GABA-induced irisin release mediates an association between sleep disturbance and sarcopenia.	[67–70]
Autonomic nervous system dysfunction	Heart rate variability studies have reported altered cardiac autonomic regulation in obstructive sleep apnea and associations between pre-sleep autonomic measures and insomnia.	Sympathetic innervation studies suggest roles for sympathetic signaling in skeletal muscle motor innervation and acetylcholine receptor stability. The vagus-nerve-mediated inflammatory reflex provides a possible indirect immune-related connection with muscle health. Lower HRV has also been reported in hospitalized older adults with sarcopenia.	HRV primarily reflects cardiac autonomic modulation and does not directly measure autonomic activity in skeletal muscle. Sympathetic neuromuscular evidence should be distinguished from vagal immune regulation. A sleep-related autonomic pathway leading to sarcopenia has not been established.	[71–76]
Malnutrition	Poorer nutritional status has been associated with poorer sleep quality in community-dwelling older adults. However, the direction of this association remains uncertain.	Lower geriatric nutritional risk index values were associated with a higher risk of incident sarcopenia in a 5-year prospective cohort.	Poor nutritional status may represent a shared risk factor for sleep disturbances and sarcopenia. Nutritional mediation of sleep-related sarcopenia remains untested, and residual confounding by frailty and comorbidities is possible.	[77,78]
Physical inactivity	Prospective polysomnographic evidence has associated lower physical activity with subsequent short sleep duration, prolonged wakefulness after sleep onset, and reduced sleep efficiency.	A meta-analysis of observational studies indicates that higher total and moderate-to-vigorous physical activity are associated with a lower risk of sarcopenia.	Physical inactivity is a potentially modifiable shared behavioral factor. However, the cited studies do not establish mediation, and sleep disturbances and sarcopenia may themselves reduce physical activity.	[79,80]

Notes: Evidence in the sleep-related and muscle-related columns may originate from separate studies and should not be interpreted as proof of a continuous causal pathway. “Direct human muscle evidence” denotes measurement of muscle outcomes following sleep manipulation, not proof of long-term sarcopenia development.

Abbreviations: AKT, protein kinase B; AMPK, AMP activated protein kinase; ATP, adenosine triphosphate; BDNF, brain-derived neurotrophic factor; CRP, C-reactive protein; FNDC5, fibronectin type III domain-containing protein 5; FoxO3a, forkhead box O3a; GABA, γ-aminobutyric acid; HRV, heart rate variability; IL-6, interleukin-6; MR, Mendelian randomization; mTOR, mechanistic target of rapamycin; NAD+, nicotinamide adenine dinucleotide; NREM, non-rapid eye movement; PGC-1α, peroxisome proliferator activated receptor gamma coactivator 1 alpha.

Circadian Rhythm Disruption

The biological clock plays a crucial role in the growth, maintenance, repair, and function of skeletal muscle. Core clock components in skeletal muscle, such as BMAL1 and CLOCK, contribute to the maintenance of skeletal muscle structure and function by regulating MyoD expression and mitochondrial homeostasis.^37,38 Skeletal muscle Bmal1 expression also participates in the regulation of total sleep duration and the response to sleep loss.³⁹ Sochal et al performed polysomnography (PSG) and sleep deprivation experiments in 81 participants and found that acute sleep deprivation significantly downregulated the expression of BMAL1 and CLOCK genes in peripheral blood.⁴⁰ Although clock gene expression in peripheral blood cannot fully represent the circadian state of skeletal muscle, these findings suggest that sleep deprivation may be associated with peripheral molecular circadian disruption. Animal studies further support a potential role of the skeletal muscle circadian clock in muscle and systemic health.⁴¹ Skeletal muscle-specific restoration of Bmal1 expression in Bmal1-knockout mice improved muscle strength, locomotor activity, glucose tolerance, and systemic inflammatory profiles, but did not affect muscle mass or fiber size. Thus, these findings provide mechanistic evidence rather than clinical evidence that circadian interventions prevent or treat sarcopenia. The clinical relevance of these pathways and their potential reversibility remain to be determined in longitudinal and intervention studies.

Neuroendocrine and Metabolic Dysregulation

With increasing age, older adults commonly experience reduced sleep efficiency and total sleep time, sleep fragmentation, circadian disruption, and reduced slow-wave sleep (SWS).⁸¹ Sleep disturbances may influence the hypothalamic-pituitary-adrenal (HPA) axis activity and muscle protein metabolism. A randomized crossover study in 13 healthy young adults found that one night of total sleep deprivation reduced muscle protein synthesis by 18% and increased cortisol levels by 21%, without significantly altering markers of muscle protein degradation.⁴² Sleep loss and poor sleep quality may also affect cortisol secretion and glucose metabolism, although the evidence linking these changes directly to age-related sarcopenia remains limited.⁴³ SWS is an important period for pulsatile growth hormone (GH) secretion, and the GH/insulin-like growth factor-1 (IGF-1) axis may contribute to the regulation of muscle and body composition.⁴⁴ Sleep loss may also reduce testosterone levels, with the effect depending partly on sleep timing and duration; however, the available evidence is based mainly on short-term experiments in young men.⁴⁵ Overall, neuroendocrine pathways provide plausible links between sleep disturbances and muscle decline, but the current evidence remains limited and does not establish a direct causal pathway to sarcopenia.

Chronic Inflammation

Chronic inflammation is a plausible shared pathway linking sleep disturbances and sarcopenia. A meta-analysis by Ballesio et al involving 35 experimental sleep deprivation studies with 887 participants showed that partial sleep deprivation for three or more consecutive nights significantly increased peripheral blood levels of interleukin-6 (IL-6) and C-reactive protein (CRP), whereas a single night of sleep deprivation did not induce similar changes.⁴⁶ These findings suggest that persistent rather than acute partial sleep restriction may be more relevant to the activation of peripheral inflammatory responses. However, the included studies were short-term experiments in healthy adults, and their relevance to sarcopenia in older adults remains uncertain. Additional population-based and mouse experimental studies have also linked severe short sleep to systemic inflammatory activity and brain inflammatory or oxidative-stress responses, although their primary outcomes were cognitive.⁸²

In a separate prospective controlled study of 63 adults aged >65 years, individuals with sarcopenia had sleep disturbances, higher tumor necrosis factor-α (TNF-α) levels, together with poorer muscle strength and physical performance.⁴⁷ Other observational studies have linked sleep improvement with reductions in CRP, IL-6, and TNF-α,⁴⁸ and reported higher IL-6 and TNF-α levels in older adults with sarcopenia.⁴⁹ Mechanistic evidence suggests that sustained inflammatory signaling, including activation of NF-κB-related pathways, may disturb muscle protein turnover and regenerative capacity.⁵⁰ Current evidence therefore supports an association among sleep disturbances, inflammation, and muscle impairment, but does not establish that inflammation mediates the development of sarcopenia.

Mitochondrial Dysfunction and Oxidative Stress

Mitochondria are essential for skeletal muscle energy metabolism and protein homeostasis. In healthy young men, five nights of sleep restriction reduced skeletal muscle mitochondrial respiratory function and sarcoplasmic protein synthesis, while exercise attenuated these changes.⁵¹ Consistent with these findings, moderate sleep restriction was associated with downregulation of skeletal muscle pathways related to the tricarboxylic acid cycle, mitochondrial translation, and complex I biogenesis.⁵² Animal findings on oxidative stress after sleep deprivation are inconsistent. One study found no evidence of lipid or protein oxidative damage in the brain, liver, or skeletal muscle after prolonged sleep deprivation, whereas other studies have reported oxidative changes.^53,54 These findings are derived mainly from animal models and vary across tissues and experimental protocols. Mitochondrial dysfunction is also implicated in sarcopenia. Human studies have reported reduced skeletal muscle mitochondrial oxidative capacity and NAD⁺ biosynthesis in individuals with sarcopenia, together with alterations in mitochondrial respiratory complexes and oxidative phosphorylation-related pathways.⁵⁵ Mechanistically, impaired mitochondrial biogenesis and dynamics, excessive mitochondrial reactive oxygen species (mtROS) production, and defective mitophagy may reduce adenosine triphosphate (ATP) availability, disrupt muscle protein homeostasis, and promote muscle atrophy.^56,57 Thus, mitochondrial and redox mechanisms may link sleep loss to muscle decline; however, the available human studies have mainly involved healthy young adults, and it remains uncertain whether sleep-related mitochondrial and redox alterations mediate the development or progression of sarcopenia in older adults.

Gut Microbiota Dysbiosis

The gut microbiota plays a pivotal role in regulating host nutrient metabolism, immune homeostasis, and the gut–muscle axis. Recent perspectives and mechanistic reviews have highlighted that sleep disruption may alter gut microbial community structure, reducing beneficial commensals while favoring inflammatory taxa.⁵⁸ Experimental studies summarized in a recent review suggest that sleep deprivation may compromise intestinal epithelial barrier integrity by downregulating tight-junction proteins, thereby facilitating the translocation of bacterial endotoxins such as lipopolysaccharide (LPS) into the circulation. This process may promote low-grade systemic inflammation and catabolic signaling.⁵⁹ Furthermore, human observational data in healthy adults indicate that shorter sleep duration is associated with decreased intestinal antimicrobial peptide secretion (human defensin 5) and reduced abundance of short-chain fatty acid (SCFA)-producing bacteria, accompanied by lower fecal SCFA levels.⁶⁰ In sarcopenic rodent models, exogenous SCFA supplementation has been demonstrated to rescue muscle mass and mitochondrial biogenesis via the activation of the protein kinase B/mammalian target of rapamycin (Akt/mTOR) and AMPK–PGC-1α pathways.⁶¹ Complementarily, Mendelian randomization studies have provided genetic evidence supporting potential causal links between specific gut microbiota, circulating metabolites, and sarcopenia-related traits.⁶² However, direct mechanistic evidence in humans remains limited, and prospective studies integrating objective sleep measurements, gut microbiome profiling, and muscle phenotypic assessments in older adults are still warranted.

Abnormal Neural Regulation

Brain-Derived Neurotrophic Factor (BDNF) and Irisin

Irisin is an exercise-responsive myokine generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), which is expressed in skeletal muscle and other tissues, including the brain.⁸³ Experimental studies suggest that FNDC5/irisin-related signaling may regulate BDNF expression. In mice and cultured neurons, exercise and experimental manipulation of FNDC5 altered hippocampal or neuronal BDNF expression.⁶³ Separately, local cortical administration or blockade of BDNF in rats bidirectionally altered subsequent non-rapid eye movement (NREM) sleep slow-wave activity, supporting a role for cortical BDNF in sleep homeostasis.⁶⁴ Human cross-sectional studies have associated lower circulating irisin levels with presarcopenia or sarcopenia⁶⁵ and with the presence and severity of OSA.⁶⁶ However, these findings do not establish that muscle-derived irisin regulates sleep through central BDNF or that this pathway mediates the association between sleep disturbances and sarcopenia in older adults.

GABAergic System

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, is an important component of sleep–wake circuitry.⁸⁴ In particular, GABAergic neurons in the preoptic hypothalamus promote sleep by inhibiting wake-promoting neuronal populations in the hypothalamus and brainstem.⁶⁷ Sleep deprivation has been shown to alter hippocampal GABA B and metabotropic glutamate receptor expression and associated synaptic plasticity in experimental models,⁶⁸ although the functional implications of these changes for sleep architecture remain unclear. Beyond its central role, emerging preclinical evidence also suggests that GABA may influence skeletal muscle homeostasis. In aged female mice, GABA administration attenuated sarcopenic changes and was associated with modulation of Akt/mTOR and forkhead box protein O3a (FoxO3a)-related signaling, reduced expression of the ubiquitin ligases muscle ring finger 1 (MuRF1) and atrogin-1, lower M1 macrophage abundance, and decreased circulating TNF-α and IL-6 levels.⁶⁹ More importantly, GABA may upregulate PGC-1α-FNDC5 signaling and induce irisin secretion from skeletal muscle cells.⁷⁰ Nevertheless, these findings are predominantly preclinical, and no direct evidence currently demonstrates that GABAergic alterations mediate the relationship between sleep disturbances and sarcopenia in older adults.

Autonomic Nervous System

Autonomic nervous system (ANS) dysfunction may be involved in the association between sleep disturbances and sarcopenia. Heart rate variability (HRV) studies have reported altered autonomic regulation in patients with OSA, while pre-sleep HRV has been associated with chronic insomnia in male national-level athletes.^71,72 However, HRV primarily reflects cardiac autonomic modulation, and findings in athletes may not generalize to older adults. Preclinical evidence suggests that sympathetic innervation contributes to skeletal muscle motor innervation and acetylcholine receptor stability, with potential implications for sarcopenia.^73,74 The vagal inflammatory reflex also regulates immune responses and may provide an indirect link between autonomic function and muscle health.⁷⁵ A cross-sectional study in hospitalized older adults reported an association between sarcopenia and lower HRV.⁷⁶ ANS dysfunction is a biologically plausible but unconfirmed mechanism linking sleep disturbances with sarcopenia. Longitudinal and intervention studies in older adults are needed to clarify whether autonomic alterations precede muscle decline.

Behavioral Factors: Physical Inactivity and Malnutrition

In addition to molecular mechanisms, poor nutritional status may be associated with both sarcopenia and poor sleep. In a 5-year prospective cohort, lower geriatric nutritional risk index values were associated with a higher risk of incident sarcopenia.⁷⁷ A cross-sectional study of 2,878 community-dwelling older adults also associated poorer nutritional status with poorer sleep quality.⁷⁸ However, the latter study cannot establish directionality, and residual confounding by frailty and comorbidities remains possible.

Lower physical activity may similarly be associated with both outcomes. Prospective polysomnographic evidence associated lower activity with higher subsequent risks of short sleep, prolonged wakefulness after sleep onset, and low sleep efficiency,⁷⁹ while observational meta-analyses associated lower activity with a higher risk of sarcopenia.⁸⁰ However, causality remains uncertain because sleep disturbances and sarcopenia may themselves reduce physical activity. Overall, poor nutritional status and physical inactivity are plausible shared modifiable correlates, but their causal and mediating roles remain unconfirmed.

Clinical Implications and Management Strategies

Sleep disturbances and sarcopenia may involve overlapping biological and behavioral pathways. Accordingly, integrated assessment and management may be clinically relevant for older adults, although their effects on sarcopenia-related outcomes remain uncertain. Current strategies include sleep assessment, management of clinically identified sleep disturbances, treatment of OSA, exercise training, nutritional interventions, and multicomponent approaches. Nevertheless, most available interventions have been evaluated in relation to either sleep-related or sarcopenia-related outcomes rather than both. Evidence that sleep-focused interventions improve muscle mass, muscle strength, or physical performance remains limited, and studies specifically targeting older adults with coexisting sleep disturbances and sarcopenia are scarce.

Screening and Clinical Assessment

Given the high prevalence and clinical consequences of sleep disturbances and sarcopenia in older adults, screening for sleep problems and sarcopenia-related features may be considered as part of comprehensive clinical assessment, particularly in geriatric, rehabilitation, primary care, and community settings. Simple tools such as the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and STOP-Bang questionnaire may help identify individuals at risk of poor sleep quality, insomnia, daytime sleepiness, or OSA. Similarly, sarcopenia screening tools such as the SARC-F questionnaire, handgrip strength testing, gait speed assessment, and calf circumference measurement may be useful in clinical and community settings. Early identification of coexisting sleep disturbances and sarcopenia-related features may help guide further diagnostic evaluation and individualized care.

Sleep Management

Multicomponent cognitive behavioral therapy for insomnia (CBT-I) is strongly recommended for adults with chronic insomnia, including older adults.^85,86 It combines stimulus control, sleep restriction or compression, cognitive restructuring, and relaxation, with sleep-hygiene education as an adjunct, and improves insomnia symptoms and sleep continuity.⁸⁷

For individuals with circadian misalignment, maintaining regular sleep–wake schedules, appropriately timed light exposure, and daytime activity may support circadian alignment and sleep.²⁸ A randomized trial in older adults with type 2 diabetes living in long-term care facilities reported improvements in subjective sleep quality and circadian rhythm measures following light therapy, although its applicability to broader populations requires further evaluation.⁸⁸ Although these interventions improve sleep, their effects on muscle health remain uncertain and warrant evaluation in trials assessing muscle mass, strength, and physical performance.

In contrast, benzodiazepines and Z-drugs may provide short-term symptom relief but are associated with cognitive impairment, delirium, falls, fractures, and dependence in older adults.⁸⁹ These concerns are particularly relevant to patients with sarcopenia or frailty. If their use is considered necessary after individualized assessment, treatment should be brief, at the lowest effective dose, and regularly reviewed.⁹⁰ Long-term users should be offered gradual deprescribing rather than abrupt discontinuation.⁹¹

Treatment of OSA

OSA is prevalent but frequently unrecognized in older adults.⁹² Continuous positive airway pressure (CPAP) is an established treatment for OSA, particularly for patients with moderate-to-severe disease or clinically significant daytime sleepiness. High-quality evidence indicates that CPAP substantially reduces the apnea–hypopnea index and improves daytime sleepiness, although treatment effectiveness depends partly on adherence.⁹³ By attenuating intermittent hypoxemia and sleep fragmentation, CPAP could theoretically benefit skeletal muscle through downstream effects on oxidative stress, inflammation, and glucose metabolism. However, evidence supporting these mechanisms is inconsistent. A small uncontrolled study of 35 patients reported changes in airway and systemic inflammatory and oxidative-stress markers after 3 months of CPAP treatment,⁹⁴ whereas a systematic review of sham-CPAP randomized trials found no consistent improvements in systemic inflammatory or metabolic biomarkers.⁹⁵ Evidence for changes in body composition is similarly preliminary: a small, nonrandomized, matched before–after study reported an increase in fat-free mass after 8 weeks of CPAP therapy;⁹⁶ however, neither handgrip strength nor appendicular skeletal muscle mass was assessed. Thus, current evidence is insufficient to establish that CPAP improves handgrip strength, gait speed, or measures of muscle mass specifically relevant to sarcopenia. Adequately powered randomized controlled trials enrolling older adults with objectively diagnosed OSA and sarcopenia are needed, with appendicular skeletal muscle mass, handgrip strength, gait speed, and chair-stand performance specified as outcomes.

Exercise Intervention

Exercise training is a key non-pharmacological strategy for managing sarcopenia and may also improve sleep-related outcomes. A 12-week randomized trial allocated 28 sarcopenic adults aged ≥65 years to resistance training or control, with 14 participants per group.⁹⁷ Resistance training improved selected polysomnographic and subjective sleep measures and muscle strength. However, the small, selected sample and short follow-up limit generalizability. Because the intervention was exercise, improvements in both domains do not establish that better sleep mediated the muscle benefit. A separate aerobic-exercise study in older adults with insomnia reported improved self-reported sleep quality and quality of life.⁹⁸ Combined aerobic and resistance training may be a practical option when both conditions coexist, but superiority over resistance training alone has not been established. Programs should be individualized to physical capacity, comorbidities and fall risk, with progressive loading to support safety and adherence.

Nutritional Intervention

Nutritional assessment and correction of malnutrition are important components of sarcopenia management. Adequate total protein intake should be prioritized, with targets individualized according to nutritional status, physical activity, renal function, comorbidities, and tolerance.⁹⁹ Protein or whey protein supplementation alone does not consistently improve muscle outcomes in older adults, but may provide additional benefits for muscle mass and strength when combined with resistance exercise, particularly in sarcopenic or frail individuals.¹⁰⁰ Among protein-derived nutrients, leucine stimulates anabolic signaling in experimental studies,¹⁰¹ but isolated leucine supplementation has not consistently improved muscle mass or strength in clinical trials.¹⁰² Its metabolite β-hydroxy-β-methylbutyrate (HMB) may be more relevant during catabolic or immobilizing conditions. A small randomized bed-rest trial found that HMB attenuated lean-mass loss,¹⁰³ while meta-analytic evidence suggests modest preservation of muscle mass but insufficient or inconsistent improvements in strength and physical performance.¹⁰⁴ Low serum 25-hydroxyvitamin D concentrations are associated with poorer muscle strength and physical performance and a higher prevalence of sleep disorders;^105,106 however, randomized evidence does not support consistent improvements in muscle mass, strength, or physical performance with vitamin D supplementation alone.¹⁰⁷ Creatine represents another potential adjunct: when combined with resistance training, it may provide additional gains in lean tissue mass and muscle strength, although evidence for creatine alone and in patients with confirmed sarcopenia or multimorbidity remains limited.¹⁰⁸ Overall, nutritional supplementation should complement rather than replace a balanced diet and resistance exercise. Direct clinical evidence that these interventions improve sarcopenia by modifying sleep remains insufficient.

Multicomponent Clinical Interventions

Given the multifactorial and potentially bidirectional relationship between sleep disturbances and sarcopenia, a multicomponent and individually tailored approach may be clinically reasonable when sleep disturbances coexist with sarcopenia or sarcopenia-related risk factors. Such an approach could combine systematic sleep assessment, identification and treatment of obstructive sleep apnea when indicated, progressive resistance exercise, adequate protein and leucine intake, correction of documented vitamin D deficiency, optimization of comorbidities and medications, fall-prevention strategies, and promotion of daytime physical activity and appropriate light exposure. However, the efficacy of this integrated model for simultaneously improving sleep health, muscle function, frailty-related outcomes, and quality of life in older adults remains uncertain and should be tested in adequately powered, pragmatic clinical trials.

Limitations and Future Perspectives

Although the association between sleep disturbances and sarcopenia has attracted increasing attention, several limitations remain in the existing literature. First, most available studies are cross-sectional, limiting conclusions regarding temporality and causal direction. Future research should prioritize large, multicenter prospective cohort studies with repeated assessments and may use complementary approaches, such as Mendelian randomization and cross-lagged panel models, while recognizing their respective methodological assumptions. Second, substantial heterogeneity exists in the assessment of sleep and sarcopenia. Sleep duration and sleep quality are often assessed using self-reported questionnaires, which are susceptible to recall and reporting bias. Sarcopenia definitions and cut-off values for muscle strength, muscle mass, and physical performance also vary across studies, limiting comparability. Future research should combine validated subjective measures with objective sleep assessments, such as actigraphy or polysomnography when appropriate, and adopt standardized sarcopenia definitions and assessment protocols. Third, multimorbidity, polypharmacy, depression, anxiety, cognitive impairment, pain, malnutrition, and restricted mobility may confound the relationship between sleep and muscle health. Future studies should appropriately address these factors in study design and analysis and investigate potential differences across populations with varying age, sex, ethnicity, comorbidity, and lifestyle characteristics.

Finally, adequately powered randomized controlled trials are needed to determine whether sleep-focused or individualized integrated interventions improve muscle mass, strength, physical performance, and other sarcopenia-related outcomes in older adults with coexisting sleep disturbances and sarcopenia.

Conclusions

Observational evidence links sleep disturbances with sarcopenia-related outcomes in older adults, although findings vary across sleep domains and sarcopenia components, and reciprocal causality remains unproven. Proposed biological pathways are plausible but have not been established as mediators in this population. Sleep assessment and management of clinically identified sleep disturbances may complement exercise and nutritional support; whether they improve sarcopenia outcomes remains uncertain. Addressing these uncertainties will require longitudinal studies with repeated objective sleep measurements and standardized sarcopenia assessments, mechanistic studies testing mediation, and adequately powered randomized trials in older adults with both conditions.

Funding Statement

No funds, grants, or other support was received.

Data Sharing Statement

No datasets were generated or analyzed during the current study.

Ethical Approval and Consent to Participate

The ethical statement is not applicable.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.