{"publication_id":"80f030f9-7eeb-47eb-bfb0-2a7392057a72","screening":{"identified":27,"screened":27,"excluded":0,"included":27,"included_or_retained":27,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"27 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["Grip strength is increasingly examined as a potential biomarker of biological aging and mortality risk, yet its independent prognostic value beyond frailty constructs remains contested.","The evidence base for grip strength as an anti-aging target is incomplete: observational associations with longevity and cognitive outcomes are consistent but confounded, while interventional data and RCT-level causal inference remain absent.","Aging societies face a fundamental question: which modifiable biomarkers reliably predict survival across the lifespan, and which merely correlate with downstream disease burden? Grip strength, a simple bedside measure of maximal voluntary force, has attracted enormous epidemiological attention as a candidate longevity signal. Across large cohorts, lower handgrip strength is associated with higher mortality risk, with hazard ratios frequently exceeding 1.3 per standard-deviation decrement, yet the field has struggled to determine whether this association reflects causal biology or residual confounding by comorbidity, physical inactivity, and frailty (Celis-Morales 2018). The clinical stakes are high: if grip strength represents a tractable anti-aging lever, it could inform exercise prescription, pharmacological targeting, and public-health screening. Conversely, if the signal is largely epiphenomenal, investing in grip strength longevity trials may divert resources from more promising gerotherapeutic strategies. The question of whether grip strength longevity extends lifespan or merely marks individuals at risk remains unresolved, and this ambiguity has persisted despite decades of observational work. This introduction frames the problem, reviews the biological rationale, surveys the evidence landscape, and identifies the gaps our synthesis aims to address.","The geroscience hypothesis posits that fundamental aging processes—cellular senescence, mitochondrial dysfunction, chronic inflammation, and proteostatic decline—drive multiple age-related diseases simultaneously, suggesting that targeting these hallmarks could compress morbidity and extend healthspan. This framework has motivated repurposing of existing drugs such as metformin and rapamycin, as well as development of novel senolytics and NAD+ precursors. Within this logic, muscle function occupies a privileged position: skeletal muscle is both a major insulin-sensitive tissue and a reservoir of amino acids critical for immune competence and wound healing. Grip strength longevity research thus emerges from two converging lines of evidence—the epidemiological observation that muscle weakness predicts mortality and the mechanistic insight that muscle-derived myokines modulate systemic inflammation and metabolic health. However, the geroscience hypothesis remains a framework, not a validated therapeutic doctrine, and its translation to clinical endpoints has been uneven. The question of whether improving grip strength longevity through exercise or pharmacology actually retards aging biology, rather than simply improving functional reserve, has been proposed but not definitively tested. This gap between mechanistic plausibility and causal proof defines the intellectual context for the present review.","Grip strength longevity, as a research construct, sits at the intersection of muscle physiology, geriatric medicine, and public health. The measure itself is inexpensive, portable, and highly reproducible, making it attractive for large-scale screening. Clinically, the European Working Group on Sarcopenia in Older People established sex-specific cutoffs—27 kg for men and 16 kg for women—that are now widely used to define probable sarcopenia and trigger further evaluation (Cruz-Jentoft 2019). Below these thresholds, individuals face elevated risk of falls, disability, and postoperative complications; for instance, grip strength appears to predict anastomotic leakage after colorectal surgery (Weak 2026) and postoperative delirium in orthopedic and oncologic populations (Arita 2021, Lee 2026). Yet grip strength is not a drug; it is a biomarker, and the leap from observational association to therapeutic target requires evidence that modifying the biomarker changes the outcome. Whether grip strength longevity interventions—resistance training, nutritional supplementation, or emerging pharmacological approaches—can achieve clinically meaningful improvements in survival remains uncertain.","The human trial landscape for grip strength longevity is dominated by observational cohort studies; randomized controlled trials with hard mortality endpoints are essentially absent. The available evidence derives predominantly from prospective registries linking baseline grip strength to subsequent events. Chair-based exercise interventions have demonstrated significant improvements in grip strength (P < 0.001; Chair-Based 2026), but these trials measure the biomarker, not survival. The heterogeneity of populations—from community-dwelling adults to hospitalized frail elders to pediatric malnutrition cases (Yldz 2026)—complicates generalizability. The question of whether grip strength longevity interventions reduce mortality in any specific subpopulation has not been answered by a single adequately powered RCT.","Several unresolved questions temper enthusiasm for grip strength longevity as a gerotherapeutic target. First, the mechanism–function gap: it remains unclear whether weak grip strength causes adverse outcomes through direct pathways such as sarcopenia-driven metabolic dysfunction, or whether it is simply a sentinel marker of global physiological reserve and accumulated damage. Second, dose–response relationships are poorly characterized; the relationship between handgrip strength and all-cause mortality appears to be modified by systemic inflammation level, with CRP thresholds of 3, 10, and 25 mg/L each yielding distinct risk profiles (TurBoned 2026), yet optimal therapeutic targets have not been defined. Third, the duration of any intervention needed to produce survival benefits is unknown; most exercise trials last weeks to months, while the epidemiological signal accumulates over years to decades. Fourth, there is the problem of competing risks—in older adults, mortality from non-musculoskeletal causes may overwhelm any benefit derived from improved grip strength alone. Evidence suggests that grip strength longevity may be most informative as part of composite frailty indices rather than as an isolated predictor, but this hypothesis requires formal testing.","The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","Mechanistically, the link between grip strength and cardiometabolic outcomes may be mediated through shared pathways involving body composition, systemic inflammation, and metabolic regulation. Clinical RCTs are needed to establish whether grip strength is a causal determinant or merely a marker of cardiometabolic health. Preclinical data suggest that skeletal muscle functions as an endocrine organ, releasing myokines that influence insulin sensitivity and vascular function, providing a plausible biological substrate for the observed associations. However, the mechanistic substrate underlying the functional finding of grip strength predicting cardiometabolic risk requires further elucidation through interventional studies.","Within this outcome class, the evidence is broadly convergent: all studies agree that HGS correlates with relevant physiologic parameters. However, a notable tension exists between the null-to-positive signal reported by most studies (Lee 2026; Najjar 2026; Yldz 2026; Ji 2026; Urbano 2026) and the negative age-related trajectory documented by Chan 2022. This tension—between HGS as a modifiable, responsive marker (Yldz 2026) and HGS as a trajectory-bound biomarker of aging (Chan 2022)—remains unresolved and has implications for intervention design.","The evidence synthesis for frailty outcomes draws on observational cohort studies examining the relationship between grip strength and frailty status in older adult populations. This population-based investigation focused on middle-aged and older adults and reported multiple statistically significant associations between frailty measures and mortality outcomes, with p-values spanning P < 0.01 to P < 0.001 across different analytic models. Wuestney 2026 employed a multiple-methods case series design using smart home technology to detect frailty in community-dwelling older adults, while Dent 2019 provided international clinical practice guidelines for identification and management of physical frailty in frail and sarcopenic adult populations."]}