Adjacent Evidence Brief: Longevity Lifespan Rates

Adjacent Evidence Brief: Longevity Lifespan Rates

Abstract

Evidence-honesty note: 7/13 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.

This paper synthesizes evidence on longevity lifespan rates across 13 accepted source papers and 271 high-confidence extracted claims.

The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 9 adjacent clinical sources, and 4 mechanistic or model-system sources, with 0 cross-study disagreements across the evidence base.

Positive study-level signals are summarized in the longevity outcome class, null signals in the contextual adjacent evidence, immune and inflammation outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.

The conclusion is that longevity lifespan rates remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Methods

Review type and protocol

This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary methods_pack.json and the timestamped submission directory synthesis-longevity_lifespan_rates-v06-DAILY-2026-06-17T04-55-05Z-R2.

Information sources

Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-17.

Search strategy

The following topic-anchored queries were executed against the information sources listed above:

• longevity lifespan rates aging
• longevity lifespan rates older adults
• longevity lifespan rates randomized controlled trial
• longevity aging
• longevity older adults
• longevity randomized controlled trial
• lifespan aging
• lifespan older adults
• lifespan randomized controlled trial

Eligibility criteria

• Sources whose primary content addresses longevity lifespan rates.
• Sources with extractable quantitative or qualitative findings.
• Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.
• Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).

Selection of sources of evidence

The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 1057 records in the receipt-candidate union, 360 were classified as source candidates and 13 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.

source admission funnel

Admission bucket	n
Receipt candidate union	1057
Classified source candidates	360
No extractable claims	277
None-only claim binding	67
Mixed partial-or-none claim-binding candidates	229
Partial-only claim-binding candidates	60
Strict high-confidence sources	64
Admitted final sources	13

Exclusion reasons

• No records were excluded at the gates instrumented for this run: the eligibility criteria above were applied during retrieval and claim-binding but produced no post-screening exclusions with recorded counts for this corpus.

Data items

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 sidecar when populated, and claim registry) rather than from re-parsed full text.

Risk-of-bias appraisal

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).

Synthesis approach

Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, longevity, 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.

AI-use disclosure

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.

Accountability

Accountability is established through reproducible artifacts: a deterministic protocol (methods_pack.json), a complete claim and citation registry, extracted numeric trace, deterministic gates (full_paper.journal_surface.json, pre_submit_gate.json, artifact_consistency.json), and a versioned correction path documented in the run's submission record. Certification under the researka_agent_certified model verifies that the manuscript is machine-verifiable, internally consistent, provenance-traced, and format-checked against these artifacts; it does not adjudicate domain correctness, corpus fit, or novelty, which remain subject to expert and reader review.

Results

Evidence domain	Corpus slice	Strongest signal	Directness	Main limitation
Longevity Lifespan Rates / Contextual Adjacent Evidence	n=8; claims=122	significant source statistic in 5/8 sources; receipt-level direction coded null	4 indirect; 4 mechanistic	limited corpus depth in this outcome class
Longevity Lifespan Rates / Longevity	n=3; claims=54	significant source statistic in 1/3 sources; receipt-level direction coded unclear	2 indirect; 1 review	limited corpus depth in this outcome class
Longevity Lifespan Rates / Immune and Inflammation	n=1; claims=27	significant source statistic in 1/1 sources; receipt-level direction coded null	1 indirect	single-source slice; hypothesis-generating
Longevity Lifespan Rates / Skeletal, Fracture, and Bone	n=1; claims=68	significant source statistic in 1/1 sources; receipt-level direction coded unclear	1 indirect	single-source slice; hypothesis-generating

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.

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Contextual Adjacent Evidence Outcomes

Contextual Adjacent Evidence remains a separate Results slice for Longevity Lifespan Rates (n=8; claims=122; significant source statistic in 5/8 sources; receipt-level direction coded null; 4 indirect; 4 mechanistic; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:

• Ayyadevara 2014 (Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans , and replicative; representative statistic P ≤ 0.05; source-level statistic reported; direction=mixed; directness=mechanistic; tier=C1).
• Zhang 2025 (Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6 -associated neurodegeneration; representative statistic P <0.05; source-level statistic reported; direction=unclear; directness=indirect; tier=B2).
• Naaz 2024 (Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction; representative statistic p < 0.0001; source-level statistic reported; direction=null; directness=indirect; tier=B2).
• Munro 2019 (The exceptional longevity of the naked mole‐rat may be explained by mitochondrial antioxidant defenses; representative statistic p < 0.0001; source-level statistic reported; direction=null; directness=mechanistic; tier=C1).

Direction reconciliation: receipt-level null or unclear coding is conservative claim-level coding. Significant but polarity-unsigned statistics remain unclear unless the extraction records a positive, negative, or mixed effect direction.

The curated corpus does not contain a long-term, hard-outcome randomized mortality trial in non-diabetic older adults, and this absence is the most consequential scope limitation of the present synthesis. Several mechanistic and preclinical sources (e. For example, Vujovic 2026 on metformin, Xu 2026 on yeast chronological lifespan, Naaz 2024 on curcumin in cells with mitochondrial dysfunction) are framed around lifespan extension, yet none provides a human survival endpoint of the kind that would license causal inference about Longevity in clinical populations. As a result, any statement of the form 'intervention X extends human lifespan' is unsupported by the present evidence base and would require a long-term mortality trial that is not represented here (Ioannidis 2005, surrogate endpoint caution). The headline conclusion that mechanistic plausibility coexists with sparse human-RCT evidence is therefore a direct reflection of this corpus gap rather than a rhetorical hedge.

A second limitation is single-trial generalization: several outcomes in the synthesis are touched by only one source and therefore cannot be internally replicated within the corpus. The PLA2G6-associated neurodegeneration lifespan result is similarly carried by one source (Zhang 2025). When a longevity claim is anchored in a single study, the synthesis cannot test robustness, cannot adjudicate between discrepant designs, and cannot exclude the possibility that the observed effect is design-specific rather than biological.

Several interventions are supported only by mechanistic evidence for a clinically relevant claim: Vujovic 2026 articulates the molecular action of metformin but stops short of clinical mortality data, and the documented preclinical lifespan extension typically attributed to metformin in animal models (~5% per Anisimov 2008) is not matched by an equivalent human survival trial in this corpus.

The curcumin and decanoic-acid lifespan signals in cells and neurodegeneration models (Naaz 2024; Zhang 2025) likewise remain on the mechanistic side of the divide.

Longevity Outcomes

Additional corpus sources included animal/preclinical evidence; longevity remains a separate Results slice for Longevity Lifespan Rates (n=3; claims=54; significant source statistic in 1/3 sources; receipt-level direction coded unclear; 2 indirect; 1 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:

• Traa 2024 (Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor; representative statistic p < 0.01; source-level statistic reported; direction=positive; directness=indirect; tier=B2).
• Medford 2019 (A Cohort Comparison of Lifespan After Age 100 in Denmark and Sweden: Are Only the Oldest Getting Older?; 8 extracted claim(s); receipt-level direction is the coded finding; direction=unclear; directness=indirect; tier=B2).
• Gong 2026 (Dendrobium officinale leaf extract extends the mean lifespan in Caenorhabditis elegans via the DAF-16/SOD-3 axis.; 2 extracted claim(s); receipt-level direction is the coded finding; direction=unclear; directness=review; tier=B1).

Immune and Inflammation Outcomes

Immune and Inflammation remains a separate Results slice for Longevity Lifespan Rates (n=1; claims=27; significant source statistic in 1/1 sources; receipt-level direction coded null; 1 indirect; single-source slice; hypothesis-generating) and is not pooled into adjacent endpoint classes. Source-level findings are:

• Hao 2026 (Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions; representative statistic p < 0.0001; source-level statistic reported; direction=null; directness=indirect; tier=B2).

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.

Population specificity further narrows the external validity of the conclusions. The synthesis therefore cannot specify which human subpopulation, if any, the lifespan signals would generalize to.

A final limitation is the persistent mechanism-to-clinic gap.

Similarly, the microbial-intervention literature (Hao 2026) and the centenarian demographic literature (Medford 2019) generate hypotheses but do not test them against hard clinical endpoints.

Until long-term, adequately powered human trials with mortality or hard functional endpoints are added to the evidence base, the Longevity case must be read as biologically suggestive but clinically unproven.

Skeletal, Fracture, and Bone Outcomes

Skeletal, Fracture, and Bone remains a separate Results slice for Longevity Lifespan Rates (n=1; claims=68; significant source statistic in 1/1 sources; receipt-level direction coded unclear; 1 indirect; single-source slice; hypothesis-generating) and is not pooled into adjacent endpoint classes. Source-level findings are:

• Yu 2025 (Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through; representative statistic p < 0.05; source-level statistic reported; direction=unclear; directness=indirect; tier=B2).

Limitations

The principal limitation is evidence-role imbalance. The retained corpus contains no sources classified primarily as direct clinical evidence, 9 adjacent clinical sources, and 4 mechanistic or model-system sources, which means causal interpretation depends on how much weight is assigned to each evidence tier.

A second limitation is endpoint heterogeneity. Study-level signals span the longevity outcome class, the contextual adjacent evidence, immune and inflammation outcome classes, no dominant outcome class, and the contextual adjacent evidence outcome class; these domains cannot be pooled narratively without losing clinically relevant differences in measurement, population, and study design.

A third limitation is that unsafe source-level numerics are excluded from public prose unless they can be tied to the correct source role and citation context. This protects the manuscript from over-specific drift but can make some sections more conservative than a free-form narrative review.

Conclusion

For longevity lifespan rates, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.

What This Synthesis Adds

This synthesis maps 13 included sources on Longevity across 4 outcome classes with no cross-study disagreements surfaced. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.

Across 13 curated reference papers, the evidence base for Longevity shows a context-dependent profile. Positive signals appear in: longevity. Null findings dominate: contextual other, immune. The Longevity 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.

In animal/preclinical evidence, prior reviews in the corpus (Gong 2026) emphasize convergent signals on Longevity. 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.

Boundary-Condition Matrix

Evidence domain	Direct sources	Indirect / mechanism sources	Direction profile	Interpretation boundary
longevity	0	3	positive, unclear	direct interventional hard-endpoint gap
immune and inflammation	0	1	null	direct interventional hard-endpoint gap
contextual adjacent evidence	0	8	mixed, null, unclear	direct interventional hard-endpoint gap
skeletal, fracture, and bone	0	1	unclear	direct interventional hard-endpoint gap

Evidence-Gap Priority

Priority	Gap	Rationale
P1	longevity: direct interventional hard-endpoint gap	0 direct and 3 indirect sources; direction profile: positive, unclear
P2	immune and inflammation: direct interventional hard-endpoint gap	0 direct and 1 indirect source; direction profile: null
P3	contextual adjacent evidence: direct interventional hard-endpoint gap	0 direct and 8 indirect sources; direction profile: mixed, null, unclear
P4	skeletal, fracture, and bone: direct interventional hard-endpoint gap	0 direct and 1 indirect source; direction profile: unclear

Next-Study Design Recommendation

The next high-yield study for Longevity should target the longevity 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.

Evidence Snapshot

The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.

Load-Bearing Included Studies

• Additional corpus sources included animal/preclinical evidence; Gong 2026; tier=B1; directness=review; endpoint=longevity; direction=unclear.
• Yu 2025; tier=B2; directness=indirect; endpoint=skeletal fracture bone; direction=unclear; representative statistic=P < 0.0001.
• Traa 2024; tier=B2; directness=indirect; endpoint=longevity; direction=positive; representative statistic=P < 0.0001.
• Hao 2026; tier=B2; directness=indirect; endpoint=immune; direction=null; representative statistic=P < 0.0001 (off-summary).
• Zhang 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=unclear; representative statistic=P < 0.0001.
• Naaz 2024; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.0001 (off-summary).
• Yu 2025b; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.
• Medford 2019; tier=B2; directness=indirect; endpoint=longevity; direction=unclear.
• Guo 2025; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null; representative statistic=P < 0.001 (off-summary).
• Ayyadevara 2014; tier=C1; directness=mechanistic; endpoint=contextual adjacent evidence; direction=mixed; representative statistic=P < 0.0004.

Source Classification Map

Each retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.

• Dendrobium officinale leaf extract extends the mean lifespan in Caenorhabditis elegans via the DAF-16/SOD-3 axis.: outcome=longevity; directness=review; tier=B1; direction=unclear; claims=2.
• Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis: outcome=skeletal fracture bone; directness=indirect; tier=B2; direction=unclear; claims=68.
• Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant: outcome=longevity; directness=indirect; tier=B2; direction=positive; claims=44.
• Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions: outcome=immune; directness=indirect; tier=B2; direction=null; claims=27.
• Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6 -associated neurodegeneration: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=unclear; claims=24.
• Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=12.
• Bridging expectations and science: a roadmap for the future of longevity interventions: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=11.
• A Cohort Comparison of Lifespan After Age 100 in Denmark and Sweden: Are Only the Oldest Getting Older?: outcome=longevity; directness=indirect; tier=B2; direction=unclear; claims=8.
• Mitochondrial Proteome Reveals Metabolic Tuning by Restricted Insulin Signaling to Promote Longevity in Caenorhabditis elegans: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=6.
• Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans , and replicative lifespan in S. cerevisiae: outcome=contextual adjacent evidence; directness=mechanistic; tier=C1; direction=mixed; claims=48.
• The exceptional longevity of the naked mole‐rat may be explained by mitochondrial antioxidant defenses: outcome=contextual adjacent evidence; directness=mechanistic; tier=C1; direction=null; claims=11.
• Molecular mechanisms of metformin action: From metabolic effects to lifespan extension and healthspan promotion: outcome=contextual adjacent evidence; directness=mechanistic; tier=C1; direction=null; claims=5.
• Yeast Chronological Lifespan Model as a Tool for Screening Aging Interventions: outcome=contextual adjacent evidence; directness=mechanistic; tier=C1; direction=null; claims=5.

Classification Criteria

• Outcome class is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.
• Directness is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.
• Directional signal is counted within the assigned outcome class only. A no extracted directional signal cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.
• Evidence tier follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.

Load-Bearing Tensions

• No load-bearing cross-study disagreements were detected.

In animal/preclinical evidence, additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Munro 2019, Studenski 2011, Cesari 2009, Cruz-Jentoft 2019.

References

• Yu 2025. Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis. Advanced Science, 2025. DOI: 10.1002/advs.202511813. PMID: 41038804.
• Ayyadevara 2014. Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans , and replicative lifespan in S. cerevisiae. Frontiers in Genetics, 2014. DOI: 10.3389/fgene.2014.00211. PMID: 25136348.
• Traa 2024. Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant. GeroScience, 2024. DOI: 10.1007/s11357-024-01276-z. PMID: 39028454.
• Hao 2026. Host Oxidative Response Capacity Determines Longevity Outcomes of Microbial Interventions. Aging Cell, 2026. DOI: 10.1111/acel.70418. PMID: 41681112.
• Zhang 2025. Decanoic acid extends lifespan and modulates metabolism in models of PLA2G6 -associated neurodegeneration. Disease Models & Mechanisms, 2025. DOI: 10.1242/dmm.052184. PMID: 41189497.
• Naaz 2024. Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction. Cells, 2024. DOI: 10.3390/cells13171470. PMID: 39273040.
• Yu 2025b. Bridging expectations and science: a roadmap for the future of longevity interventions. Biogerontology, 2025. DOI: 10.1007/s10522-025-10278-z. PMID: 40591010.
• Munro 2019. The exceptional longevity of the naked mole‐rat may be explained by mitochondrial antioxidant defenses. Aging Cell, 2019. DOI: 10.1111/acel.12916. PMID: 30768748.
• Medford 2019. A Cohort Comparison of Lifespan After Age 100 in Denmark and Sweden: Are Only the Oldest Getting Older?. Demography, 2019. DOI: 10.1007/s13524-018-0755-7. PMID: 30659510.
• Guo 2025. Mitochondrial Proteome Reveals Metabolic Tuning by Restricted Insulin Signaling to Promote Longevity in Caenorhabditis elegans. Biology, 2025. DOI: 10.3390/biology14030279. PMID: 40136535.
• Vujovic 2026. Molecular mechanisms of metformin action: From metabolic effects to lifespan extension and healthspan promotion. Journal of Medical Biochemistry, 2026. DOI: 10.5937/jomb0-60849. PMID: 41821769.
• Xu 2026. Yeast Chronological Lifespan Model as a Tool for Screening Aging Interventions. International Journal of Molecular Sciences, 2026. DOI: 10.3390/ijms27062633. PMID: 41898496.
• Gong 2026. Dendrobium officinale leaf extract extends the mean lifespan in Caenorhabditis elegans via the DAF-16/SOD-3 axis. Biogerontology, 2026. DOI: 10.1007/s10522-026-10456-7. PMID: 42249998.

Background References

Canonical reference values and methodological references cited in prose. Each entry's citation_token appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).

• Studenski 2011. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58. DOI: 10.1001/jama.2010.1923. PMID: 21205966.
• Cesari 2009. Cesari M, Kritchevsky SB, Newman AB, et al. Added value of physical performance measures in predicting adverse health-related events. J Gerontol A Biol Sci Med Sci. 2009;64(7):772-779. DOI: 10.1093/gerona/glp012. PMID: 19349594.
• Cruz-Jentoft 2019. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31. DOI: 10.1093/ageing/afy169. PMID: 30312372.
• Anisimov 2008. Anisimov VN, Berstein LM, Egormin PA, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle. 2008;7(17):2769-2773. PMID: 18728386.
• Ioannidis 2005. Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124. (methodological reference) DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.