# Two-year caloric restriction × reduced PC PhenoAge and PC GrimAge: a checklist of measure-specific evidence gaps Verdict 2941 · Evidence Check Stored-material review date: Not recorded Original evidence cut-off: 2026-08-26 Review-criteria version: 1.0 Public page/material preparation date: 2026-10-11 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Healthy non-obese adults in CALERIE; three US sites; detailed eligibility not read - Ingredient, formulation and route: Historical two-year caloric-restriction study intervention; not personal calorie, diet or weight-loss instructions - Dose: Original target of 25% and achieved average of about 12% preserved separately; individual and time-specific exposure details not read - Comparator: Parent randomized control group; specific control diet, support and concurrent management not read - Measured outcome: Selected reductions in PC PhenoAge and PC GrimAge; unverified measure-specific values and time points, and DunedinPACE preserved separately - Duration: Two-year study intervention; details of DunedinPACE at 12 and 24 months and time-specific PC outcomes unverified; post-intervention follow-up unverified - Questions outside this scope: Recasting a DNA measure as clinical rejuvenation, aging in general, disease, disability, death, lifespan or independent living; Treating target exposure and the achieved average as identical; Summing time points, measures, the 197-person DNA denominator or sibling sheets as new independent evidence; Personal calorie, dietary, weight-loss or treatment instructions ## Checklist items ### N01 · Are the original PC PhenoAge and PC GrimAge claim and subclaim assessment separated from the parent slowing context? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original subclaim is 'Reduced PC PhenoAge and PC GrimAge', with grade D and a note that neither measure changed significantly. The parent overall assessment, including DunedinPACE, is C54 with Unknown safety. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The subclaim has no score, status or axes; parent values are not used to fill them. No new assessment is made. - Reason for missing information: The subclaim has no score, status or axes; parent values are not used to fill them. No new assessment is made. - Required materials and conditions: Records of the subclaim's original wording, grade and note and the parent context - Materials to obtain first: The subclaim has no score, status or axes; parent values are not used to fill them. No new assessment is made. - Further research: Connect additional original material for each measure separately to the subclaim question and parent context. - Conditions for verification: Records of the subclaim's original wording, grade and note and the parent context - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N02 · Do the two PC measures concern healthy non-obese adults? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original paper is a post hoc analysis of 220 healthy non-obese adults in CALERIE at three US sites. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Findings are not automatically extended to direct effects in aging-related disease, obesity, other ages or frail populations. Detailed eligibility and baseline values have not been read. - Reason for missing information: Findings are not automatically extended to direct effects in aging-related disease, obesity, other ages or frail populations. Detailed eligibility and baseline values have not been read. - Required materials and conditions: Eligibility, baseline condition, age, BMI and group denominators - Materials to obtain first: Findings are not automatically extended to direct effects in aging-related disease, obesity, other ages or frail populations. Detailed eligibility and baseline values have not been read. - Further research: Obtain original population and baseline characteristics and numbers analyzed for each measure. - Conditions for verification: Eligibility, baseline condition, age, BMI and group denominators - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N03 · Are the 25% target and about 12% achieved restriction distinguished as study exposures? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original target is recorded as 25%, with average achieved restriction of about 12%. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. These are historical study conditions rather than personal calorie or weight-loss targets. The two PC findings are not assumed to be effects of the target exposure. - Reason for missing information: These are historical study conditions rather than personal calorie or weight-loss targets. The two PC findings are not assumed to be effects of the target exposure. - Required materials and conditions: Original plans, achieved restriction, duration, adherence and measurements - Materials to obtain first: These are historical study conditions rather than personal calorie or weight-loss targets. The two PC findings are not assumed to be effects of the target exposure. - Further research: Obtain original exposure measurements, individual adherence, restriction achieved over time and support records. - Conditions for verification: Original plans, achieved restriction, duration, adherence and measurements - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N04 · Is the actual comparison of control diets, support and concurrent changes available? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The parent's randomized two-year caloric-restriction context is preserved. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Detailed control diets, exposures, contact and support are absent from the original summary. Equivalent nutrient composition or weight changes are not invented. - Reason for missing information: Detailed control diets, exposures, contact and support are absent from the original summary. Equivalent nutrient composition or weight changes are not invented. - Required materials and conditions: Actual diets, contact, support and concurrent management by group - Materials to obtain first: Detailed control diets, exposures, contact and support are absent from the original summary. Equivalent nutrient composition or weight changes are not invented. - Further research: Obtain original intervention, control, support, achieved-exposure and concurrent-change material. - Conditions for verification: Actual diets, contact, support and concurrent management by group - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N05 · Are 220 randomized participants and the 197-person DNA analysis time-specific PC denominators? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: There were 220 participants randomized 2:1; the DNA analysis included 197 participants with baseline and at least one follow-up sample. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Group sizes are not calculated from 2:1 allocation. The 197 participants are not assumed to be the denominator for all PC outcomes at 12 or 24 months. - Reason for missing information: Group sizes are not calculated from 2:1 allocation. The 197 participants are not assumed to be the denominator for all PC outcomes at 12 or 24 months. - Required materials and conditions: Group allocation, DNA samples and analysis denominators by measure and time - Materials to obtain first: Group sizes are not calculated from 2:1 allocation. The 197 participants are not assumed to be the denominator for all PC outcomes at 12 or 24 months. - Further research: Obtain group samples and analysis flows and denominators by time and measure. - Conditions for verification: Group allocation, DNA samples and analysis denominators by measure and time - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N06 · Are gaps in DNA sample selection, missingness, follow-up and models preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account requires baseline and at least one follow-up sample for DNA inclusion. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Group exclusions, time-specific missingness, ITT, data processing and sensitivity analyses have not been read. New attrition rates or differences are not calculated. - Reason for missing information: Group exclusions, time-specific missingness, ITT, data processing and sensitivity analyses have not been read. New attrition rates or differences are not calculated. - Required materials and conditions: Missingness, selection, analysis populations, sensitivity analyses and models by measure - Materials to obtain first: Group exclusions, time-specific missingness, ITT, data processing and sensitivity analyses have not been read. New attrition rates or differences are not calculated. - Further research: Obtain original DNA selection, missingness, models and sensitivity material. - Conditions for verification: Missingness, selection, analysis populations, sensitivity analyses and models by measure - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N07 · Are the definition, units and original individual effects of PC PhenoAge directly available? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: PC PhenoAge is one of the three original measures and is recorded as not significantly changed. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The endpoints of the d −0.04 to 0.05 range in the original rationale are not assigned as a particular time-specific PC PhenoAge effect. Individual CIs, P values and unit details have not been read. - Reason for missing information: The endpoints of the d −0.04 to 0.05 range in the original rationale are not assigned as a particular time-specific PC PhenoAge effect. Individual CIs, P values and unit details have not been read. - Required materials and conditions: Definitions, units, time points, denominators, effects and intervals for individual measures - Materials to obtain first: The endpoints of the d −0.04 to 0.05 range in the original rationale are not assigned as a particular time-specific PC PhenoAge effect. Individual CIs, P values and unit details have not been read. - Further research: Obtain original PC PhenoAge definitions, effects, CIs, P values and denominators by time. - Conditions for verification: Definitions, units, time points, denominators, effects and intervals for individual measures - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N08 · Are the definition, units and original individual effects of PC GrimAge directly available? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: PC GrimAge is also one of the three original measures and is recorded as not significantly changed. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The endpoints of the d range are not assigned as a particular PC GrimAge effect. Individual CIs, P values, denominators and algorithm definitions have not been read. - Reason for missing information: The endpoints of the d range are not assigned as a particular PC GrimAge effect. Individual CIs, P values, denominators and algorithm definitions have not been read. - Required materials and conditions: Definitions, units, time points, denominators, effects and intervals for individual measures - Materials to obtain first: The endpoints of the d range are not assigned as a particular PC GrimAge effect. Individual CIs, P values, denominators and algorithm definitions have not been read. - Further research: Obtain original PC GrimAge definitions, effects, CIs, P values and denominators by time. - Conditions for verification: Definitions, units, time points, denominators, effects and intervals for individual measures - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N09 · Are the d range and P threshold presented jointly for the two measures distinguished from individual values? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account describes the two PC measures as null, with d −0.04 to 0.05 and P>0.15. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The range is not converted into a new mean, point estimates for each measure, exact P values or CIs. Zero effects or equivalence are not certified. - Reason for missing information: The range is not converted into a new mean, point estimates for each measure, exact P values or CIs. Zero effects or equivalence are not certified. - Required materials and conditions: Detailed tables of original effects, intervals and tests by measure and time - Materials to obtain first: The range is not converted into a new mean, point estimates for each measure, exact P values or CIs. Zero effects or equivalence are not certified. - Further research: Obtain original tables of individual effects, CIs, tests, models and denominators. - Conditions for verification: Detailed tables of original effects, intervals and tests by measure and time - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N10 · Are PC outcomes at 12 and 24 months preserved separately by time? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original rationale gives DunedinPACE results at 12 and 24 months specifically, but describes the two PC measures as null only within a summary range. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Time-specific DunedinPACE d values, CIs and P values are not copied as PC values. Individual time-specific PC values remain unverified. - Reason for missing information: Time-specific DunedinPACE d values, CIs and P values are not copied as PC values. Individual time-specific PC values remain unverified. - Required materials and conditions: PC values, changes, between-group effects and denominators at each time - Materials to obtain first: Time-specific DunedinPACE d values, CIs and P values are not copied as PC values. Individual time-specific PC values remain unverified. - Further research: Obtain original tables and analysis denominators for both PC measures at each time. - Conditions for verification: PC values, changes, between-group effects and denominators at each time - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N11 · Has the positive DunedinPACE signal been kept separate from PC reductions? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original DunedinPACE signal is preserved: d=−0.29 (95% CI −0.45 to −0.13) at 12 months, d=−0.25 (−0.41 to −0.09) at 24 months, original P<0.003 and roughly 2~3% slowing. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. This measure's slowing is not used to fill in reductions in PC PhenoAge or PC GrimAge. A 24-month CI level or individual P values are not newly added. - Reason for missing information: This measure's slowing is not used to fill in reductions in PC PhenoAge or PC GrimAge. A 24-month CI level or individual P values are not newly added. - Required materials and conditions: Results, units, time points and direct original effects by measure - Materials to obtain first: This measure's slowing is not used to fill in reductions in PC PhenoAge or PC GrimAge. A 24-month CI level or individual P values are not newly added. - Further research: Connect original effects, intervals, time points and models separately by measure. - Conditions for verification: Results, units, time points and direct original effects by measure - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N12 · Do the PC age measures and DunedinPACE pace measure quantify the same thing? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account separates three DNA-methylation clocks or measures and describes DunedinPACE as a surrogate pace-of-aging measure. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Pace changes, PC reductions and clinical aging itself are not combined as the same value. Exact measure-specific definitions, units and validation have not been read. - Reason for missing information: Pace changes, PC reductions and clinical aging itself are not combined as the same value. Exact measure-specific definitions, units and validation have not been read. - Required materials and conditions: Purpose, definitions, units, validation and applicability of each measure - Materials to obtain first: Pace changes, PC reductions and clinical aging itself are not combined as the same value. Exact measure-specific definitions, units and validation have not been read. - Further research: Obtain original methods, units and validation material separately for each measure. - Conditions for verification: Purpose, definitions, units, validation and applicability of each measure - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N13 · Are DNA laboratory methods, batches, normalization and PC calculation directly preserved? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The design is a post hoc DNA-methylation analysis; the original account records laboratory analyst blinding. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. PC algorithm, measurement, batch and normalization details are not invented, and new PC scores are not calculated from original data. - Reason for missing information: PC algorithm, measurement, batch and normalization details are not invented, and new PC scores are not calculated from original data. - Required materials and conditions: Original methods for samples, platforms, batches, normalization and PC calculation - Materials to obtain first: PC algorithm, measurement, batch and normalization details are not invented, and new PC scores are not calculated from original data. - Further research: Obtain original laboratory, measure-calculation and data-processing methods. - Conditions for verification: Original methods for samples, platforms, batches, normalization and PC calculation - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N14 · Are the post hoc analysis and the parent's prespecified clinical primary plan separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The paper is explicitly post hoc, and the original account states that this was not the parent's prespecified clinical primary endpoint. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The two PC measures are not newly designated as prespecified clinical coprimary endpoints. Registration and SAP remain unread in this production. - Reason for missing information: The two PC measures are not newly designated as prespecified clinical coprimary endpoints. Registration and SAP remain unread in this production. - Required materials and conditions: Original registration, protocol, SAP, analysis selection, changes and hierarchy - Materials to obtain first: The two PC measures are not newly designated as prespecified clinical coprimary endpoints. Registration and SAP remain unread in this production. - Further research: Obtain parent plans and records of post hoc measure selection, hierarchy and changes. - Conditions for verification: Original registration, protocol, SAP, analysis selection, changes and hierarchy - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N15 · Are the split findings across three key measures and plans for multiple time points and tests preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original assessment that only one of three measures was positive and the parent's split-key-measures flag set to true are preserved. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The original split-results axis is not converted into a prespecified clinical primary designation. Adjustments for nonsignificant PC findings or positive DunedinPACE findings are not invented. - Reason for missing information: The original split-results axis is not converted into a prespecified clinical primary designation. Adjustments for nonsignificant PC findings or positive DunedinPACE findings are not invented. - Required materials and conditions: Original plans for three measures, time points, effects of interest, multiplicity and selective reporting - Materials to obtain first: The original split-results axis is not converted into a prespecified clinical primary designation. Adjustments for nonsignificant PC findings or positive DunedinPACE findings are not invented. - Further research: Obtain tests and adjustments by measure and time, original outcome lists and selective-reporting records. - Conditions for verification: Original plans for three measures, time points, effects of interest, multiplicity and selective reporting - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N16 · Are null or nonsignificant findings distinguished from exclusion of a clinically important effect or equivalence? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account states that there was no clinical minimum-effect threshold or prespecified success boundary and records null findings for both PC measures. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. P>0.15 without individual CIs does not newly certify exclusion of all meaningful reductions or equivalence. - Reason for missing information: P>0.15 without individual CIs does not newly certify exclusion of all meaningful reductions or equivalence. - Required materials and conditions: Individual CIs, validated thresholds and prespecified success boundaries - Materials to obtain first: P>0.15 without individual CIs does not newly certify exclusion of all meaningful reductions or equivalence. - Further research: Obtain original CIs, clinical-importance validation and prespecified plans for each PC measure. - Conditions for verification: Individual CIs, validated thresholds and prespecified success boundaries - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N17 · Are blinding and allocation procedures recorded at their actual measure-specific scope? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original Korean account says analysts were unaware of allocation; the English account specifies 'laboratory analysts blinded'. The 2:1 randomized design is preserved. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Participant, intervention-provider or all-analyst blinding and allocation concealment are not described as newly verified. - Reason for missing information: Participant, intervention-provider or all-analyst blinding and allocation concealment are not described as newly verified. - Required materials and conditions: Parent allocation, laboratory analysts, statistical analysis and measurement methods - Materials to obtain first: Participant, intervention-provider or all-analyst blinding and allocation concealment are not described as newly verified. - Further research: Obtain original allocation, laboratory and analyst roles and blinding procedures. - Conditions for verification: Parent allocation, laboratory analysts, statistical analysis and measurement methods - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N18 · Is the relationship between achieved exposure, weight or nutrient changes and PC effects directly verified? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original information that target and achieved average restriction differed is preserved. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. PC effects by achieved restriction, mechanisms and causal relationships with weight changes are not newly calculated or confirmed. - Reason for missing information: PC effects by achieved restriction, mechanisms and causal relationships with weight changes are not newly calculated or confirmed. - Required materials and conditions: Achieved restriction, adherence, concurrent changes and prespecified mediation or effects of interest - Materials to obtain first: PC effects by achieved restriction, mechanisms and causal relationships with weight changes are not newly calculated or confirmed. - Further research: Obtain original achieved exposure, adherence, concurrent changes, models and plans. - Conditions for verification: Achieved restriction, adherence, concurrent changes and prespecified mediation or effects of interest - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N19 · Do gaps remain concerning post-intervention persistence, later measures and mechanisms? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original intervention lasted two years, and the stored summary has no quantitative post-intervention PC persistence effects. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Post-intervention PC reductions, rebound or all-mechanism effects are not invented. - Reason for missing information: Post-intervention PC reductions, rebound or all-mechanism effects are not invented. - Required materials and conditions: Follow-up duration, measures, denominators, original effects and direct mechanism measurements - Materials to obtain first: Post-intervention PC reductions, rebound or all-mechanism effects are not invented. - Further research: Obtain direct post-intervention measures, models, denominators and follow-up material. - Conditions for verification: Follow-up duration, measures, denominators, original effects and direct mechanism measurements - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N20 · Do null PC findings establish null results for all clinical aging, disease or lifespan outcomes? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account states that reduced disease, disability or death was not measured and healthy lifespan was not answered. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Null PC findings are not recast as null clinical effects overall; the DunedinPACE signal is not recast as benefits for rejuvenation, lifespan or independent living. - Reason for missing information: Null PC findings are not recast as null clinical effects overall; the DunedinPACE signal is not recast as benefits for rejuvenation, lifespan or independent living. - Required materials and conditions: Direct clinical endpoints, follow-up, events, denominators and effects - Materials to obtain first: Null PC findings are not recast as null clinical effects overall; the DunedinPACE signal is not recast as benefits for rejuvenation, lifespan or independent living. - Further research: Direct events, long-term follow-up and original effects are needed for each clinical question. - Conditions for verification: Direct clinical endpoints, follow-up, events, denominators and effects - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N21 · Are the same CALERIE report, measures and time points kept from being counted as new independent replication? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Both subclaim sheets share the same post hoc paper, 220 randomized participants and 197-person DNA data. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Different measures, time points or sheets are not summed as independent trials or new participants. Final unique trial, participant and independent counts remain unrecorded. - Reason for missing information: Different measures, time points or sheets are not summed as independent trials or new participants. Final unique trial, participant and independent counts remain unrecorded. - Required materials and conditions: Relationships among the parent trial, post hoc report, same participants and sibling sheets - Materials to obtain first: Different measures, time points or sheets are not summed as independent trials or new participants. Final unique trial, participant and independent counts remain unrecorded. - Further research: Connect additional reports through original trial identifiers while retaining same-population relationships. - Conditions for verification: Relationships among the parent trial, post hoc report, same participants and sibling sheets - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N22 · Are funding, DunedinPACE inventors and commercial licensing preserved alongside the PC findings? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Support from NIA, American Brain Foundation, CIHR and others, authorship by DunedinPACE inventors D.L. Corcoran and D.W. Belsky, and commercial licensing are preserved. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The same invention or licensing interests are not newly added for the PC measures. Product or service provision, employee affiliations and outside-analysis details have not been read. - Reason for missing information: The same invention or licensing interests are not newly added for the PC measures. Product or service provision, employee affiliations and outside-analysis details have not been read. - Required materials and conditions: Funding, invention, licensing, affiliations, provision and analysis roles - Materials to obtain first: The same invention or licensing interests are not newly added for the PC measures. Product or service provision, employee affiliations and outside-analysis details have not been read. - Further research: Obtain original funding, measure-related disclosures, affiliations, analysis and manuscript roles. - Conditions for verification: Funding, invention, licensing, affiliations, provision and analysis roles - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N23 · Are absent safety reporting in this analysis and parent-trial harms separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: This post hoc analysis did not report safety as an endpoint, and original safety is Unknown. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Null PC findings or positive DunedinPACE findings are not used as evidence of safety. They are not extended to absence of all harms in the parent CALERIE trial. - Reason for missing information: Null PC findings or positive DunedinPACE findings are not used as evidence of safety. They are not extended to absence of all harms in the parent CALERIE trial. - Required materials and conditions: Analysis-specific and parent-trial harm plans, collection, events by group and denominators - Materials to obtain first: Null PC findings or positive DunedinPACE findings are not used as evidence of safety. They are not extended to absence of all harms in the parent CALERIE trial. - Further research: Obtain original parent-trial harm collection, events, exposure, discontinuation and denominators. - Conditions for verification: Analysis-specific and parent-trial harm plans, collection, events by group and denominators - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N24 · What gaps concern achieved two-year exposure, rare harms, discontinuation and long-term follow-up? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original account explicitly states that this analysis cannot determine harms of long-term caloric restriction. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Harm counts, rates, CIs or specific nutritional harms outside the original account are not invented. Null results for two measures are not assumed to mean no harms. - Reason for missing information: Harm counts, rates, CIs or specific nutritional harms outside the original account are not invented. Null results for two measures are not assumed to mean no harms. - Required materials and conditions: Direct harms by group exposure, severity, discontinuation and duration - Materials to obtain first: Harm counts, rates, CIs or specific nutritional harms outside the original account are not invented. Null results for two measures are not assumed to mean no harms. - Further research: Obtain original trial and follow-up harm, exposure, discontinuation and rare-event material. - Conditions for verification: Direct harms by group exposure, severity, discontinuation and duration - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N25 · Are harm replication, applicability and instructions for other populations or dietary exposures distinguished? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The current material concerns historical two-year study conditions in healthy non-obese adults. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Effects or harms for other populations or dietary methods are not newly confirmed; personal calorie, diet, weight-loss or treatment guidance is not created. - Reason for missing information: Effects or harms for other populations or dietary methods are not newly confirmed; personal calorie, diet, weight-loss or treatment guidance is not created. - Required materials and conditions: Direct effects or harms and report relationships by population and exposure - Materials to obtain first: Effects or harms for other populations or dietary methods are not newly confirmed; personal calorie, diet, weight-loss or treatment guidance is not created. - Further research: Connect direct comparison and harm material for new populations or exposures separately. - Conditions for verification: Direct effects or harms and report relationships by population and exposure - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N26 · Are the stored summary and actual access to external abstracts, full text, registration and SAP distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original PubMed link and NCT00427193 are preserved, and the entire parent summary was read for production. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. A registration URL is not newly constructed, and all external materials remain unread. Separate links, screens and content review were not checked during original production. - Reason for missing information: A registration URL is not newly constructed, and all external materials remain unread. Separate links, screens and content review were not checked during original production. - Required materials and conditions: Original links, registration identifiers, preserved original material and material-specific access records - Materials to obtain first: A registration URL is not newly constructed, and all external materials remain unread. Separate links, screens and content review were not checked during original production. - Further research: Connect provided original material with its actual material-specific access status. - Conditions for verification: Original links, registration identifiers, preserved original material and material-specific access records - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ### N27 · Are the reference date, Korean and English text, empty values, subclaim and parent values, and production status preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The 2026-08-26 reference date, empty correction and deliberation values, Korean and English text, parent C54, original axes and subclaim D are preserved. Original pending and production-eligible markers are historical. - Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The absent subclaim score is not filled in. The original content review remains incomplete; model, content and scope review activation and completion remain false, added assessment units are 0 and the final independent count is unrecorded. - Reason for missing information: The absent subclaim score is not filled in. The original content review remains incomplete; model, content and scope review activation and completion remain false, added assessment units are 0 and the final independent count is unrecorded. - Required materials and conditions: Distinction among original text, assessment records, dates, corrections, candidate history and review status - Materials to obtain first: The absent subclaim score is not filled in. The original content review remains incomplete; model, content and scope review activation and completion remain false, added assessment units are 0 and the final independent count is unrecorded. - Further research: Proposal: Reflect additional materials and decisions through preservation of original wording and separate events. - Conditions for verification: Distinction among original text, assessment records, dates, corrections, candidate history and review status - Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits - Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Reduced PC PhenoAge and PC GrimAge - Related sources: R01 ## Evidence and sources ### R01 Waziry R, Ryan CP, Corcoran DL, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging. 2023;3:248-257. PMID: 37118425. [PubMed](https://pubmed.ncbi.nlm.nih.gov/37118425/) Materials actually read: Summary read; external materials not read Findings recorded in the summary: Only DunedinPACE changed: d=−0.29 at 12 months and d=−0.25 at 24 months; the other two clocks were null Record level: Stored evidence-list and narrative summaries; not direct reading of the original paper or registration Independent replication: Post hoc DNA analysis of the CALERIE parent randomized trial; the two subclaim sheets, measures and time points are shared, rather than separate new trials. Family IDs connect relationships and do not certify unique trial counts; reports, time points, measures, sibling sheets and the same participants are not newly summed as independent evidence. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | local_summary | Original source link preserved | Summary read | Summary read | Preserved parent verdict summary | | abstract | Original source link preserved | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | fulltext | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | registration | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | protocol_sap | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because results are unreported. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. ## What the statuses mean - Partly verified: Some information exists in the preserved review summary; detailed original materials remain unverified. This does not certify a passed review or clinical efficacy. - Unverified: Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety - Review incomplete: Review of existing content incomplete - Met: Use only within the relevant conditions after existing content review; no automatic designation in this preparation - Not reported: Distinguish only within materials actually read; do not turn unread external materials into unreported findings - Inaccessible: Not applied during this preparation because actual access was not tested - Not applicable: Use with a reason for non-applicability based on an explicit question boundary - Conflicting data: Judge after actual material comparison; review was not performed during this preparation - Insufficient evidence for the conditions: Do not use as a clinical grade encompassing currently unread materials ## Change history 2026-10-11 · Public page/materials 1.0. Public pages and materials were prepared from the existing 27 items. No new clinical search, verification-status change or scoring was performed.