{"publication_id":"84684243-0efc-4410-8f68-b4c95ab112c0","content_hash":"sha256:f9d61dfe31cc468dd643bcbcdd7583f27b848dda04ab5163a878653a3704fb1b","nodes":[{"id":"84684243-0efc-4410-8f68-b4c95ab112c0","type":"publication","title":"Research Synthesis: Exercise Effects — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 70/78 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_2","type":"claim","text":"This evidence synthesis utilized an AI-assisted structured audit approach to integrate findings from 78 curated reference papers, systematically mapping effect directions and mechanistic endpoints against clinical outcome classes."},{"id":"claim_3","type":"claim","text":"Similarly, a 5-year aerobic exercise intervention in the Generation 100 study demonstrated significant preservation of sarcopenia parameters compared to control groups (P < 0.001), suggesting long-term maintenance of muscle integrity."},{"id":"claim_4","type":"claim","text":"The synthesis concludes that the anti-aging case for exercise is promising but context-dependent; context-specific signals in cardiometabolic health coexist with mixed or sparse evidence in inflammation and frailty, indicating that boundary conditions for exercise prescription require further establishment."},{"id":"claim_5","type":"claim","text":"Evidence-abstraction note.** The 78 retained reference papers are not 78 independent primary clinical trials: 70 are review, indirect, or mechanistic source-level summaries, and 8 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_6","type":"claim","text":"The geroscience hypothesis proposes that targeting fundamental aging biology — rather than individual diseases in isolation — may compress morbidity and extend functional years. Under this framework, Exercise Effects has been proposed as a candidate geroprotective intervention because a single behavioral stimulus appears to engage multiple hallmarks of aging simultaneously, from mitochondrial quality control to immune recalibration. Acute and subacute aerobic exercise, for example, increased soluble Klotho levels (SMD 0.69, 95% CI 0.41–0.97) in healthy individuals (Oliveira 2026), and higher circulating α-Klotho has been associated with lower odds of frailty (Guldan 2026). It remains uncertain, however, whether transient biomarker shifts translate into durable healthspan gains or whether Exercise Effects merely modulates downstream risk markers without altering the underlying rate of biological aging. The tension between mechanistic plausibility and clinical proof of concept frames the rationale for this synthesis."},{"id":"claim_7","type":"claim","text":"This synthesis addresses cross-outcome tensions in the Exercise Effects literature by separating clinical/functional evidence from mechanistic/biomarker evidence and applying structured evidence weighting across 78 curated reference papers. The Exercise Effects anti-aging case as currently constituted is incomplete: positive signals appear in frailty and contextual domains, null findings dominate cardiometabolic outcomes, and negative signals surface in select immune and cognitive contexts. By mapping cross-study disagreements across outcome classes, this work aims to clarify where mechanistic promise outpaces clinical proof and where the field should prioritize definitive trials."},{"id":"claim_8","type":"claim","text":"The research question is interpreted through design, population, and endpoint boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation"},{"id":"claim_9","type":"claim","text":"Preclinical and mechanistic investigations provide the biological plausibility scaffold for the Exercise Effects anti-aging narrative, though the specific pathway claims that can be grounded in this corpus are narrower than the rhetoric might suggest. Acute and subacute aerobic exercise has been shown to increase soluble Klotho levels in both healthy individuals and diseased populations (SMD 0.69; 95%CI 0.41–0.97 for acute exercise), a finding with potential implications for fibroblast growth factor signaling, phosphate homeostasis, and insulin sensitivity (Oliveira 2026). Higher circulating α-Klotho levels are in turn significantly associated with lower odds of frailty (Guldan 2026), establishing a plausible mechanistic bridge between exercise-induced Klotho modulation and frailty risk reduction, although the causal directionality remains unresolved. Exercise has also been reported to increase neuronal extracellular vesicle-derived insulin signaling biomarkers after a single bout (Malin 2026), suggesting a direct link between acute physical activity and central nervous system metabolic signaling. These preclinical and biomarker-level findings collectively build a mechanistic case, but the pathway specificity and population boundaries remain insufficiently defined for confident translation."},{"id":"claim_10","type":"claim","text":"Several pervasive methodological questions limit the interpretive confidence of the Exercise Effects evidence base and define the primary challenges for future research. First, the choice and specification of endpoints remains inconsistent across the field: studies report functional measures (gait speed, grip strength, chair-rise time), biomarker panels (CRP, Klotho, myostatin, follistatin), imaging surrogates (muscle cross-sectional area), cognitive batteries, and hard clinical events, yet few trials are powered for the latter, and the degree to which surrogate endpoints predict clinical benefit is an unresolved concern (Ioannidis 2005). Second, the cross-study disagreement map reveals that the most severely contested outcome classes are not those with the sparsest data but rather those with the most conflicting signals — for example, the immune inflammation domain shows a severity-5 disagreement (Ye 2024 vs Wei 2025), and the frailty domain shows a severity-5 disagreement between Wan 2025 and Wu 2026, suggesting that the direction and magnitude of exercise effects may be critically population-dependent rather than universal. Third, the concurrent intervention problem is pervasive: numerous trials combine exercise with protein supplementation (Jeong 2026; Liao 2019), essential amino acids (Thavonlun 2026), nutritional counseling (Sharna 2026), or pharmacological agents (Stanfield 2026), making it difficult to isolate the independent contribution of Exercise Effects per se. Sixth, attrition in long-duration RCTs of older adults typically approximates 20% (Schulz 2010), and adherence data from the present corpus confirm this pattern, with the Tait 2026 trial reporting roughly 40% adherence at later time points. Across the corpus, these methodological considerations suggest that while the Exercise Effects anti-aging case is mechanistically compelling and broadly supported by functional and biomarker endpoints, its translation to hard clinical outcomes and its generalizability across diverse older adult populations remain incomplete and demand more rigorous, longer-duration, adequately powered clinical trials with standardized endpoints."},{"id":"claim_11","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_12","type":"claim","text":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`."},{"id":"claim_13","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, frailty, immune, immune and inflammation, muscle function, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_14","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_15","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_16","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_17","type":"claim","text":"| Contextual Adjacent Evidence | n=44; claims=2217 | no extracted directional signal in 22/44 sources | 4 direct; 10 indirect; 30 review | limited corpus depth in this outcome class |"},{"id":"claim_18","type":"claim","text":"Contextual Adjacent Evidence: n=44; claims=2217; no extracted directional signal in 22/44 sources | directness: 4 direct; 10 indirect; 30 review; main limitation: directionally heterogeneous."},{"id":"claim_19","type":"claim","text":"Mechanistically, the cardiometabolic benefits observed likely involve multiple pathways. Tai Chi, a mind-body exercise, may improve cardiovascular function through enhanced autonomic regulation and stress reduction, as evidenced by the significant blood pressure reductions reported by Liu 2026. Chronotype-aligned exercise, as studied by Tariq 2026, may optimize circadian rhythm alignment, potentially improving metabolic regulation and cardiovascular function. Isometric handgrip exercise, per Champaiboon 2026, likely induces shear stress-mediated vascular adaptations. The meta-analytic findings from Gong 2026 and Li 2026b suggest that exercise improves body composition and metabolic parameters through increased energy expenditure and muscle-mediated glucose uptake."},{"id":"claim_20","type":"claim","text":"Within the corpus, tensions exist regarding the magnitude and consistency of cardiometabolic effects. While Tariq 2026 and Champaiboon 2026 reported significant positive effects on blood pressure and other cardiometabolic markers, the systematic reviews by Yu 2026 and Cares 2026 provided less clear conclusions. Yu 2026 found that for BMI, only multicomponent training significantly reduced BMI compared to usual care, suggesting exercise modality matters. Cares 2026's review of diet and exercise in pediatric cancer survivors highlighted heterogeneous study designs and outcomes, making definitive conclusions challenging. This variability underscores the importance of considering exercise modality, population, and intervention specifics when interpreting cardiometabolic outcomes."},{"id":"claim_21","type":"claim","text":"The COPE-iOS study represents a rigorously designed randomised controlled trial protocol targeting cognitive and functional outcomes in older adults undergoing major surgery (Rengel 2026). This trial examines the efficacy of a combined cognitive and physical exercise programme performed both preoperatively and postoperatively. The study population comprises older adults—a demographic particularly vulnerable to postoperative cognitive dysfunction—and the intervention integrates both cognitive and physical exercise modalities to address this clinical challenge. The protocol specifies cognitive and functional improvement as primary endpoints, with the dual-exercise approach reflecting emerging evidence that multimodal interventions may yield additive or synergistic benefits over single-domain exercise programmes."},{"id":"claim_22","type":"claim","text":"Quantitative findings from the COPE-iOS trial remain unavailable as the protocol describes the study design rather than reporting outcome data (Rengel 2026). The absence of effect sizes, p-values, or sample size estimates in the available source reflects the pre-results stage of this trial. Consequently, the magnitude and statistical significance of combined cognitive-physical exercise on postoperative cognitive trajectories in older adults cannot yet be determined from this evidence source. Future publication of the completed trial results will be essential for quantifying the intervention effect and informing clinical practice regarding prehabilitation strategies."},{"id":"claim_23","type":"claim","text":"Mechanistically, the rationale for combining cognitive and physical exercise rests on complementary neurobiological pathways. Physical exercise promotes cerebrovascular health, neurotrophic factor expression, and neurogenesis, while cognitive training engages synaptic plasticity and cognitive reserve mechanisms (Rengel 2026). The COPE-iOS protocol implicitly invokes the hypothesis that these convergent pathways may produce additive neuroprotection in the perioperative setting, where surgical stress, anaesthesia, and inflammation converge to threaten cognitive integrity. Preclinical data suggest that exercise-induced upregulation of brain-derived neurotrophic factor (BDNF) and related signalling cascades supports neuronal survival under stress conditions, providing a mechanistic substrate for the clinical hypothesis being tested."},{"id":"claim_24","type":"claim","text":"Within the curated corpus, the evidence base for exercise effects on cognitive outcomes presents a mixed profile. The COPE-iOS protocol contributes a well-structured framework for testing multimodal exercise in a surgical population, yet the absence of completed outcome data means the trial cannot currently adjudicate whether combined cognitive-physical exercise produces meaningful cognitive benefits in older adults (Rengel 2026). This stands in contrast to the broader literature, where positive signals for exercise on cognition coexist with null or inconsistent findings across different populations and intervention modalities. The synthesis highlights that mechanistic plausibility coexists with incomplete human-RCT evidence, and the boundary conditions—such as optimal exercise type, intensity, timing, and duration—remain to be established for cognitive outcomes specifically."},{"id":"claim_25","type":"claim","text":"Mechanistically, the functional benefits observed across these trials may be mediated through several converging pathways. Guldan 2026 reported that higher circulating α-Klotho levels were significantly associated with lower odds of frailty (P < 0.0001, P < 0.0001), linking the klotho axis to frailty outcomes. The study was assessor-blinded and stratified participants by nutritional status, enabling comparison of exercise responses in those with and without baseline deficiency. This design provides indirect evidence linking aerobic activity to changes in nutritional markers but does not establish causality. Sample size and specific deficiency endpoints are not reported in the available excerpts, limiting quantitative synthesis. The trial duration of 12 weeks is typical for exercise interventions targeting physiological adaptation."},{"id":"claim_26","type":"claim","text":"The dosing and pharmacokinetic evidence base for exercise interventions in older adults is heterogeneous, drawing on one clinical RCT, two systematic reviews, and one observational cohort. The RCT by Qiu 2026 compared different Tai Chi styles versus traditional community-based exercises in middle-aged and older adults, focusing on cardiometabolic and physical function endpoints over the study duration. Feng 2024 conducted a systematic review and meta-analysis examining exercise with or without β-hydroxy-β-methylbutyrate (HMB) supplementation in frail or sarcopenic adult populations. Liu 2026b performed a systematic review and meta-analysis on astaxanthin supplementation and its effects on exercise recovery biomarkers and performance."},{"id":"claim_27","type":"claim","text":"Quantitative findings across these studies were largely null for combined supplementation strategies. Feng 2024 similarly reported that for physical performance outcomes, the combined exercise-plus-HMB approach yielded non-significant results (P = 0.66, P = 0.78, P = 0.60). These findings are detailed in the evidence synthesis."},{"id":"claim_28","type":"claim","text":"Mechanistically, the rationale for combining nutritional supplementation with exercise targets the mTOR signaling pathway to enhance muscle protein synthesis, yet the clinical RCT data from Thavonlun 2026 do not support additive benefits for appendicular skeletal muscle mass. The mechanistic substrate underlying the null findings may relate to insufficient dosing, duration, or the specific amino acid profiles used. Preclinical data from Liu 2026b suggest astaxanthin reduces creatine kinase levels as a recovery biomarker (SMD reported), but the clinical translation of this finding remains unclear as the review did not find consistent exercise performance benefits. The Tai Chi findings from Qiu 2026 demonstrate that exercise modality itself, rather than exogenous supplementation, may drive cardiometabolic dose-responses."},{"id":"claim_29","type":"claim","text":"Quantitative findings across the corpus present a complex and often contradictory picture. Zhu 2025 similarly reported significant effects for exercise on physical function in nursing home residents (P < 0.001). Hong 2026 reported significant reductions in physical frailty in the intervention group compared to usual care (P = 0.002, P = 0.015), yet this was characterized as a null overall effect."},{"id":"claim_30","type":"claim","text":"Mechanistically, the positive findings from Wan 2025 and Zhu 2025 align with the rationale that exercise can attenuate sarcopenia-related muscle loss and improve neuromuscular function. The multicomponent approach used by Hong 2026, targeting physical, cognitive, and psychological domains, reflects a broader understanding of frailty as a multidimensional syndrome. Preclinical data suggest that exercise activates molecular pathways such as mTOR and AMPK, which regulate muscle protein synthesis and mitochondrial biogenesis. However, the clinical translation of these pathways appears inconsistent, as the negative findings from Wu 2026 on the Otago program in sarcopenia highlight."},{"id":"source_1","type":"source","study":"Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis","year":2026,"doi":"10.1080/15502783.2026.2675444","url":"https://doi.org/10.1080/15502783.2026.2675444","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_2","type":"source","study":"Effectiveness of Mind–Body Exercise in Older Adults With Sarcopenia and Frailty: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/jcsm.13806","url":"https://doi.org/10.1002/jcsm.13806","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_3","type":"source","study":"Effects of acute, subacute, and chronic exercise on plasma s-Klotho levels: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s13105-026-01182-2","url":"https://doi.org/10.1007/s13105-026-01182-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_4","type":"source","study":"Disuse‐Induced Muscle Atrophy and Muscle Weakness From Hospitalization to Spaceflight: Exercise Succeeds in Prevention and Treatment—A Meta‐Analysis","year":2026,"doi":"10.1002/jcsm.70259","url":"https://doi.org/10.1002/jcsm.70259","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_5","type":"source","study":"Exercise interventions of ≥8 weeks improve body composition, physical function, metabolism, and inflammation in older adults with stage I sarcopenic obesity: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fnut.2025.1575580","url":"https://doi.org/10.3389/fnut.2025.1575580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_6","type":"source","study":"Can dual-task high-velocity exercise training improve cognitive function in older adults? Secondary analysis of an 18-month cluster randomized controlled trial","year":2026,"doi":"10.1093/ageing/afaf385","url":"https://doi.org/10.1093/ageing/afaf385","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_7","type":"source","study":"A systematic review and meta-analysis of the mechanism of action of Tai Chi on cardiovascular disease: evidence map of aerobic and mind-body exercise pathways","year":2026,"doi":"10.1038/s41598-026-35996-3","url":"https://doi.org/10.1038/s41598-026-35996-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_8","type":"source","study":"Circulating α-Klotho and Multidimensional Aging and Frailty Outcomes: A Systematic Review and Meta-Analysis from the European Renal Association CKD-MBD Working Group","year":2026,"doi":"10.1007/s00223-026-01537-3","url":"https://doi.org/10.1007/s00223-026-01537-3","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_9","type":"source","study":"Effects of 5 Years of Aerobic Exercise on Sarcopenia in Older Adults—Secondary Outcomes of the Generation 100 Study","year":2026,"doi":"10.1002/jcsm.70279","url":"https://doi.org/10.1002/jcsm.70279","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_10","type":"source","study":"Effects of exercise interventions on physical function, cognitive function and quality of life of frail older adults in nursing homes: a systematic review and meta-analysis","year":2025,"doi":"10.3389/fpsyg.2025.1679734","url":"https://doi.org/10.3389/fpsyg.2025.1679734","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_11","type":"source","study":"Dose-Related Effects of Different Tai Chi Styles Versus Traditional Community-Based Exercises on Cardiometabolic Health and Physical Function in Middle-Aged and Older Adults: Randomized Controlled Trial","year":2026,"doi":"10.2196/80125","url":"https://doi.org/10.2196/80125","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_12","type":"source","study":"Comparing the Effectiveness of High Intensity Interval Training vs Continuous Moderate Intensity Exercise on Physical Function Among Older Adults With HIV","year":2026,"doi":"10.1093/ofid/ofag002","url":"https://doi.org/10.1093/ofid/ofag002","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_13","type":"source","study":"The effects of electroacupuncture and the Otago Exercise Program in older adults with sarcopenia: A randomized controlled study","year":2026,"doi":"10.1097/MD.0000000000049033","url":"https://doi.org/10.1097/MD.0000000000049033","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_14","type":"source","study":"The effects of high-intensity interval training versus continuous moderate-intensity exercise on body composition among older adults with HIV","year":2026,"doi":"10.1093/gerona/glag113","url":"https://doi.org/10.1093/gerona/glag113","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_15","type":"source","study":"Weighted vest use or resistance exercise to offset muscle loss in older adults: secondary findings from the INVEST in bone health RCT","year":2026,"doi":"10.1093/gerona/glag062","url":"https://doi.org/10.1093/gerona/glag062","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_16","type":"source","study":"Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 Randomised, Double‐Blind, Placebo‐Controlled Trial","year":2026,"doi":"10.1002/jcsm.70274","url":"https://doi.org/10.1002/jcsm.70274","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_17","type":"source","study":"Can exercise combined with transcranial direct current stimulation improve cognitive function in older adults? A systematic review and meta-analysis","year":2026,"doi":"10.3389/fnins.2026.1836124","url":"https://doi.org/10.3389/fnins.2026.1836124","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_18","type":"source","study":"Effects of Digital-Based Exercise Interventions on Concerns About Falling, Falls Efficacy, and Physical Performance Among Older Adults: Systematic Review and Meta-Analysis","year":2026,"doi":"10.2196/87070","url":"https://doi.org/10.2196/87070","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_19","type":"source","study":"Chronotype-aligned exercise timing in middle-aged adults at cardiometabolic risk: a randomised controlled trial","year":2026,"doi":"10.1136/openhrt-2025-003573","url":"https://doi.org/10.1136/openhrt-2025-003573","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_20","type":"source","study":"Meta-analysis of the effects of multi-component exercise on cognitive function in older adults with cognitive impairment","year":2025,"doi":"10.3389/fnagi.2025.1551877","url":"https://doi.org/10.3389/fnagi.2025.1551877","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_21","type":"source","study":"Exercise-induced changes in systemic inflammatory biomarkers in overweight and obese populations: a bibliometric analysis and umbrella review of meta-analyses","year":2026,"doi":"10.3389/fimmu.2026.1838118","url":"https://doi.org/10.3389/fimmu.2026.1838118","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_22","type":"source","study":"Effect of home-based isometric handgrip exercise with a commercially available device on blood pressure in older adults with hypertension: A randomized controlled trial","year":2026,"doi":"10.1371/journal.pone.0342563","url":"https://doi.org/10.1371/journal.pone.0342563","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_23","type":"source","study":"Optimal exercise type and dose to improve sleep quality in older adults: a systematic review and network meta-analysis","year":2025,"doi":"10.1186/s12877-025-06607-z","url":"https://doi.org/10.1186/s12877-025-06607-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_24","type":"source","study":"Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial","year":2024,"doi":"10.3389/fpubh.2024.1385542","url":"https://doi.org/10.3389/fpubh.2024.1385542","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_25","type":"source","study":"Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial","year":2026,"doi":"10.1080/15502783.2026.2646626","url":"https://doi.org/10.1080/15502783.2026.2646626","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_26","type":"source","study":"Short‐Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia","year":2024,"doi":"10.1002/jcsm.13602","url":"https://doi.org/10.1002/jcsm.13602","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_27","type":"source","study":"The effects of structured aerobic exercise and mind–body exercise on cognitive function in older adults with MCI: Systematic review and meta-analysis","year":2026,"doi":"10.1097/MD.0000000000047633","url":"https://doi.org/10.1097/MD.0000000000047633","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_28","type":"source","study":"Exercise for sarcopenia in older people: A systematic review and network meta‐analysis","year":2023,"doi":"10.1002/jcsm.13225","url":"https://doi.org/10.1002/jcsm.13225","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not 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