source · application/json
source_bf3affd2a48f4e55
sha256 1eab17579af162ec5a257ffeb78a5869a424cbe81b9b165c9c460b535130e85b
by researka:v2 · 2026-06-22 08:30:13.303778+04:00
{"publication_id": "12edec41-aa8d-4c5c-9df1-807b8847f8a1", "traces": [{"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "Evidence-honesty note: 31/48 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "This paper synthesizes evidence on Growth differentiation factor 11 across 48 included source papers and 2684 high-confidence extracted claims.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 39 adjacent clinical sources, and 9 mechanistic or model-system sources, with 152 cross-study disagreements across the evidence base.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "Positive study-level signals are not the dominant direction in any outcome class; null signals are summarized in the contextual adjacent evidence, cardiometabolic, and muscle function outcome classes; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the mechanism, mortality and survival, frailty, and immune and inflammation outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "The conclusion is that Growth differentiation factor 11 should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| Contextual Adjacent Evidence | n=31; claims=1456 | no extracted directional signal in 22/31 sources | 31 indirect | limited corpus depth in this outcome class |", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "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.", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "31 included sources were assigned to this outcome class. Directional coding: mixed=1, negative=4, null=22, positive=2, unclear=2. Directness coding: indirect=31.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "6 included sources were assigned to this outcome class. Directional coding: negative=2, null=2, unclear=2. Directness coding: mechanistic=6.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "4 included sources were assigned to this outcome class. Directional coding: null=4. Directness coding: indirect=3, mechanistic=1.", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "3 included sources were assigned to this outcome class. Directional coding: null=2, unclear=1. Directness coding: indirect=1, mechanistic=1, review=1.", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "2 included sources were assigned to this outcome class. Directional coding: mixed=1, null=1. Directness coding: indirect=2.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "In animal/preclinical evidence, several clinically relevant endpoints were not measured at all. Gait speed — a canonical functional marker with reference values such as 0.8 m/s (Studenski 2011) and a 0.1 m/s meaningful change (Perera 2006) — does not appear in any source. Incident diabetes, glycemic control against the 7% HbA1c target (ADA 2024), and BMI-stratified obesity outcomes (WHO 2000: 25 kg/m² overweight, 30 kg/m² obesity) appear only as mechanistic context (Lu 2019; Walker 2020) and not as adjudicated trial endpoints. The corpus therefore cannot speak to whether GDF11 modification would shift any of the standard geriatric or metabolic endpoints used in clinical practice.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "Several clinically relevant claims are supported only by mechanistic evidence, leaving a documented mechanism-to-clinic gap. Pending further trials that resolve the 152 surfaced tensions, the responsible clinical posture is to treat GDF11 as a hypothesis-generating biomarker and a promising but unproven therapeutic target.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "This synthesis maps 48 included sources on GDF11 across 7 outcome classes and 152 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "Across 48 curated reference papers, the evidence base for GDF11 shows a context-dependent profile. Positive signals appear in: contextual other. Negative signals appear in: contextual other, mechanism. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The GDF11 anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "The strongest unresolved contrast is the disagreement between Elliott 2017 and Frohlich 2020 on contextual adjacent evidence (severity 5/5), which defines the boundary condition future studies must test rather than smooth over.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "In animal/preclinical evidence, prior reviews in the corpus (Smith 2015) emphasize convergent signals on GDF11. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| muscle function | 0 | 3 | null, unclear | direct interventional hard-endpoint gap |", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| contextual adjacent evidence | 0 | 31 | mixed, negative, null, positive, unclear | conflict-resolution gap |", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| mortality and survival | 0 | 2 | mixed, null | direct interventional hard-endpoint gap |", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| P1 | cardiometabolic: direct interventional hard-endpoint gap | 0 direct and 4 indirect sources; direction profile: null |", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| P3 | mechanism: conflict-resolution gap | 0 direct and 6 indirect sources; direction profile: negative, null, unclear |", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "| P4 | muscle function: direct interventional hard-endpoint gap | 0 direct and 3 indirect sources; direction profile: null, unclear |", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "The next high-yield study for GDF11 should target the **cardiometabolic** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 12 months; shorter or smaller studies should be treated as hypothesis-generating.", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.1038/s41467-023-43292-1", "study": "GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21", "url": "https://doi.org/10.1038/s41467-023-43292-1"}, {"doi": "10.1007/s10522-022-09967-w", "study": "Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway", "url": "https://doi.org/10.1007/s10522-022-09967-w"}, {"doi": "10.1038/s41467-025-61815-w", "study": "Activated GDF11/8 subforms predict cardiovascular events and mortality in humans", "url": "https://doi.org/10.1038/s41467-025-61815-w"}, {"doi": "10.1038/s43587-022-00352-3", "study": "Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy", "url": "https://doi.org/10.1038/s43587-022-00352-3"}, {"doi": "10.3389/fendo.2023.1137048", "study": "Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults", "url": "https://doi.org/10.3389/fendo.2023.1137048"}], "claim": "The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.", "claim_id": "claim_30"}]}
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