# Two-year caloric restriction × slower DunedinPACE: a post hoc DNA-surrogate evidence checklist 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 slower-DunedinPACE question; the two PC measures and clinical outcomes kept separate - 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 DunedinPACE subclaim assessment and the parent pace-of-aging context kept separate? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The subclaim concerns 'Slower DunedinPACE', with original grade C and a note of a roughly 2~3% slowing signal. The parent surrogate assessment is C, 54 points and 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. This is not a new clinical assessment. - Reason for missing information: The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment. - Required materials and conditions: Separate records of the original claim, grade, note and parent values - Materials to obtain first: The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment. - Further research: If additional original material is provided, connect the selected measure separately from the parent context. - Conditions for verification: Separate records of the original claim, grade, note and parent values - 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: Slower DunedinPACE - Related sources: R01 ### N02 · What population and applicability limits concern healthy non-obese adults? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original population was healthy non-obese adults, and CALERIE took place 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. Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations. - Reason for missing information: Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations. - Required materials and conditions: Age, baseline condition, obesity status, eligibility and population-specific denominators - Materials to obtain first: Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations. - Further research: Obtain original eligibility, baseline characteristics and recruitment denominators. - Conditions for verification: Age, baseline condition, obesity status, eligibility and population-specific 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: Slower DunedinPACE - Related sources: R01 ### N03 · Are the target caloric restriction and achieved average exposure distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The historical study target was 25% restriction, whereas the original account reports 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. The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read. - Reason for missing information: The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read. - Required materials and conditions: Study records of the original target, achieved exposure, measurement, adherence and duration - Materials to obtain first: The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read. - Further research: Obtain original exposure measurements, adherence, support and change records. - Conditions for verification: Study records of the original target, achieved exposure, measurement, adherence 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: Slower DunedinPACE - Related sources: R01 ### N04 · Can the intervention and control diets, support and concurrent exposures over two years be verified? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original intervention was two-year caloric restriction, and the positive finding is recorded as a randomized comparison with a control group. - 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. Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed. - Reason for missing information: Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed. - Required materials and conditions: Actual intervention and control diets, support, contact and concurrent management - Materials to obtain first: Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed. - Further research: Connect protocol records of the control, support, achieved exposure and concurrent management. - Conditions for verification: Actual intervention and control diets, support, contact and concurrent management - 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: Slower DunedinPACE - Related sources: R01 ### N05 · Do 220 randomized participants, 2:1 allocation and the 197-person DNA sample share a denominator? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: CALERIE randomized 220 participants in a 2:1 ratio. DNA data were analyzed for 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 newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months. - Reason for missing information: Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months. - Required materials and conditions: Randomization, sample acquisition, measure-specific analyses and time-specific denominators - Materials to obtain first: Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months. - Further research: Obtain original tables tracing allocation, DNA samples and analyses by time and measure. - Conditions for verification: Randomization, sample acquisition, measure-specific analyses and time-specific 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: Slower DunedinPACE - Related sources: R01 ### N06 · Do gaps remain concerning DNA sample selection, follow-up, missingness and the effect of interest? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original DNA analysis requirement of baseline and at least one follow-up sample 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. Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated. - Reason for missing information: Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated. - Required materials and conditions: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models - Materials to obtain first: Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated. - Further research: Obtain original sample-selection, group-specific missingness, analysis-population and sensitivity plans. - Conditions for verification: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models - 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: Slower DunedinPACE - Related sources: R01 ### N07 · Is DunedinPACE a pace measure distinct from clinical events? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account describes DunedinPACE as a DNA-methylation measure of the pace of aging and a surrogate rather than a clinical event. - 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 result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read. - Reason for missing information: The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read. - Required materials and conditions: DNA measure definitions, measurement units, validation and measurement procedures - Materials to obtain first: The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read. - Further research: Obtain original measure definitions, validation, measurement, units and clinical-linkage material. - Conditions for verification: DNA measure definitions, measurement units, validation and measurement procedures - 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: Slower DunedinPACE - Related sources: R01 ### N08 · Are details of DNA measurement, batches, normalization and measure calculation available? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The post hoc DNA-methylation design and analyst blinding 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. Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated. - Reason for missing information: Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated. - Required materials and conditions: Original methods for samples, DNA measurement, batches, normalization and algorithms - Materials to obtain first: Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated. - Further research: Obtain original laboratory, measure-calculation and quality-processing methods. - Conditions for verification: Original methods for samples, DNA measurement, batches, normalization and algorithms - 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: Slower DunedinPACE - Related sources: R01 ### N09 · Are the original 12-month DunedinPACE effect and CI preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account records the 12-month effect as d=−0.29 (95% CI −0.45 to −0.13). - 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 standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read. - Reason for missing information: The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read. - Required materials and conditions: Original effects, units, CIs, models and denominators by time - Materials to obtain first: The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read. - Further research: Obtain the original 12-month model, adjustments, denominators, effect and CI. - Conditions for verification: Original effects, units, CIs, models and denominators by 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: Slower DunedinPACE - Related sources: R01 ### N10 · Is the 24-month DunedinPACE effect and interval preserved as a separate time-specific value? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original wording d=−0.25 (−0.41 to −0.09) at 24 months 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. The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated. - Reason for missing information: The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated. - Required materials and conditions: Original effects, original intervals, models and denominators by time - Materials to obtain first: The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated. - Further research: Obtain the original 24-month effect, interval level, model and time-specific denominators. - Conditions for verification: Original effects, original intervals, models and denominators by 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: Slower DunedinPACE - Related sources: R01 ### N11 · What is the scope of P<0.003 and the roughly 2~3% wording? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original rationale presents the DunedinPACE values at 12 and 24 months together with P<0.003. The reader answer and note describe 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. The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life. - Reason for missing information: The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life. - Required materials and conditions: Links between time-specific tests, effect transformations and original estimates - Materials to obtain first: The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life. - Further research: Obtain the original definitions and models for time-specific tests and percentage wording. - Conditions for verification: Links between time-specific tests, effect transformations and original estimates - 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: Slower DunedinPACE - Related sources: R01 ### N12 · Are the null PC PhenoAge and PC GrimAge findings preserved together? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account describes the other two 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 endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks. - Reason for missing information: The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks. - Required materials and conditions: Original effects, intervals and tests by distinct measure and time - Materials to obtain first: The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks. - Further research: Obtain effects, CIs, P values and denominators separately for each PC measure and time. - Conditions for verification: Original effects, intervals and tests by distinct 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: Slower DunedinPACE - Related sources: R01 ### N13 · Do the pace measure and the two PC clocks use the same units and address the same question? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account distinguishes a result in which only one of three DNA-methylation measures 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 pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read. - Reason for missing information: The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read. - Required materials and conditions: Definitions, reference standards, units and interpretation limits for each measure - Materials to obtain first: The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read. - Further research: Obtain original definitions, validation, units and applicability material for each measure. - Conditions for verification: Definitions, reference standards, units and interpretation limits for 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: Slower DunedinPACE - Related sources: R01 ### N14 · Are the post hoc analysis and the parent's prespecified clinical primary endpoint distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The paper explicitly identifies the analysis as post hoc. The original account states that the DNA outcomes were not the parent trial'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 DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized. - Reason for missing information: The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized. - Required materials and conditions: Original registration, protocol, SAP, analysis timing and outcome hierarchy - Materials to obtain first: The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized. - Further research: Obtain original registration, protocol and SAP, and records of post hoc analysis selection and changes. - Conditions for verification: Original registration, protocol, SAP, analysis timing and outcome 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: Slower DunedinPACE - Related sources: R01 ### N15 · Are the split findings across three measures and the multiple-outcome analysis plan preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account assesses only one of three measures as positive and the key measures as split; the parent split-key-measures flag remains true. - 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 parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read. - Reason for missing information: The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read. - Required materials and conditions: Original plans for three measures, time points, models, tests and multiplicity handling - Materials to obtain first: The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read. - Further research: Obtain the DNA analysis's original outcome list, time points, tests, adjustments and selective-reporting plan. - Conditions for verification: Original plans for three measures, time points, models, tests and multiplicity handling - 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: Slower DunedinPACE - Related sources: R01 ### N16 · Is the absence of a clinical minimum-effect threshold and prespecified success boundary preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account records no clinical minimum-effect threshold or prespecified success boundary and describes the effects as small. - 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. Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects. - Reason for missing information: Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects. - Required materials and conditions: Clinical validation, minimum-effect thresholds and plans for each measure - Materials to obtain first: Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects. - Further research: Connect clinical validation, prespecified thresholds and plans for each measure if provided. - Conditions for verification: Clinical validation, minimum-effect thresholds and plans for 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: Slower DunedinPACE - Related sources: R01 ### N17 · What is the original scope of allocation and analyst blinding? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The Korean account says that analysts did not know allocation; the English account specifies 'laboratory analysts blinded'. The parent's 2:1 randomized design is also 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. Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read. - Reason for missing information: Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read. - Required materials and conditions: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures - Materials to obtain first: Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read. - Further research: Obtain original allocation, laboratory and measure-analysis methods and blinding roles. - Conditions for verification: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures - 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: Slower DunedinPACE - Related sources: R01 ### N18 · Is the relationship between achieved restriction, adherence, weight changes and measure effects directly verified? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The 25% target and average achieved restriction of about 12% are preserved as historical study conditions. - 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 of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms. - Reason for missing information: Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms. - Required materials and conditions: Original achieved exposure, adherence, concurrent changes and effects of interest - Materials to obtain first: Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms. - Further research: Obtain achieved exposure, adherence, concurrent changes and prespecified mediation or effect-of-interest material. - Conditions for verification: Original achieved exposure, adherence, concurrent changes and 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: Slower DunedinPACE - Related sources: R01 ### N19 · Do gaps remain concerning persistence after 12 or 24 months, mechanisms and other aging measures? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original DNA effects are presented at 12 and 24 months, and the intervention lasted two years. - 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. Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in. - Reason for missing information: Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in. - Required materials and conditions: Follow-up measures, duration, denominators, original effects and direct mechanism evidence - Materials to obtain first: Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in. - Further research: Obtain direct post-intervention follow-up and original measurements, denominators and effects separately by measure. - Conditions for verification: Follow-up measures, duration, denominators, original effects and direct mechanism evidence - 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: Slower DunedinPACE - Related sources: R01 ### N20 · Has the result been kept separate from disease, disability, death, lifespan and independent-living outcomes? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original account explicitly states that reduced disease, disability or death was not measured and longer healthy life 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. The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living. - Reason for missing information: The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living. - Required materials and conditions: Direct clinical endpoints, adequate follow-up, events, denominators and effects - Materials to obtain first: The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living. - Further research: Direct definitions, long-term follow-up, denominators and effect data are needed for each clinical outcome. - Conditions for verification: Direct clinical endpoints, adequate 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: Slower DunedinPACE - Related sources: R01 ### N21 · Are the two sibling sheets, two time points and one post hoc report kept from being independently summed? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Both sheets share the same CALERIE post hoc report and the 220-person and 197-person context. - 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. Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded. - Reason for missing information: Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded. - Required materials and conditions: Relationships among the parent trial, post hoc report, same participants, measures and time points - Materials to obtain first: Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded. - Further research: Link additional reports through original trial identifiers while retaining relationships to the same population. - Conditions for verification: Relationships among the parent trial, post hoc report, same participants, measures and time points - 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: Slower DunedinPACE - Related sources: R01 ### N22 · Are funding and DunedinPACE invention and commercial-licensing interests distinguished? 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 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. Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read. - Reason for missing information: Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read. - Required materials and conditions: Funding, authors, invention, licensing, provision and analysis roles - Materials to obtain first: Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read. - Further research: Obtain original funding, licensing, affiliations, product or service provision, analysis and manuscript roles separately. - Conditions for verification: Funding, authors, invention, licensing, 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: Slower DunedinPACE - Related sources: R01 ### N23 · Does absent safety reporting establish that the parent trial had no harms? 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 the parent's safety assessment 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. Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE. - Reason for missing information: Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE. - Required materials and conditions: Harm plans, events by group and exposure denominators for this analysis and the parent trial - Materials to obtain first: Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE. - Further research: Obtain the parent trial's original harm plans, events by group, exposure, discontinuation and denominators separately. - Conditions for verification: Harm plans, events by group and exposure denominators for this analysis and the parent trial - 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: Slower DunedinPACE - Related sources: R01 ### N24 · Do gaps remain concerning long-term or rare harms under two-year achieved exposure? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original safety account 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. Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented. - Reason for missing information: Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented. - Required materials and conditions: Direct harm data by achieved exposure, discontinuation, severity and duration - Materials to obtain first: Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented. - Further research: Obtain group-specific harms, discontinuation, rare events and long-term data from the parent trial and follow-up reports. - Conditions for verification: Direct harm data by achieved exposure, discontinuation, severity 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: Slower DunedinPACE - Related sources: R01 ### N25 · Are harm replication, applicability to other populations or exposures, and dietary instructions distinguished? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The current population is healthy non-obese adults, and the historical exposure is a two-year study with differing target and achieved average 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. Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created. - Reason for missing information: Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created. - Required materials and conditions: Direct effects, harms, exposures and same-population relationships by population - Materials to obtain first: Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created. - Further research: Connect direct comparisons and harm evidence for new populations or exposures separately. - Conditions for verification: Direct effects, harms, exposures and same-population relationships by population - 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: Slower DunedinPACE - Related sources: R01 ### N26 · Are the stored summary, PubMed link and registration identifier distinguished from materials actually read? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The whole parent summary was read for production, and the original PubMed link and NCT00427193 identifier were connected. - 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 new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested. - Reason for missing information: A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested. - Required materials and conditions: Separate access records for the summary, abstract, full text, registration, protocol and SAP - Materials to obtain first: A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested. - Further research: Connect additional provided material with its individual access status. - Conditions for verification: Separate access records for the summary, abstract, full text, registration, protocol and SAP - 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: Slower DunedinPACE - Related sources: R01 ### N27 · Are original dates, Korean and English text, empty values, subclaim and parent values, and review 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, C54, original axes and subclaim C are preserved. Original pending and production-eligible markers are historical; content review at that time remained incomplete. - 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 missing subclaim score and unrecorded precision are not filled in. Original 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 missing subclaim score and unrecorded precision are not filled in. Original 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 the complete original, selected assessment record, history and current production status - Materials to obtain first: The missing subclaim score and unrecorded precision are not filled in. Original 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 the complete original, selected assessment record, history and current production 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: Slower DunedinPACE - 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.