mTORiX›Caloric Restriction (CR)
Intervention · Evidence map

Caloric Restriction (CR)

Sustained energy-intake reduction. In the CALERIE Phase 2 human trial, participants were ASSIGNED a 25% caloric-restriction target but ACHIEVED a substantially smaller mean reducti...

Class: Dietary intervention (sustained reduction in caloric intake relative to ad libitum/baseline)Lit. search: 2026-07-11v0.2.0-mvp
Reviewed by Nabus Research · last reviewed 2026-07-11 · about our review process
Human lifespan evidence: none

Classification

Intervention class: Dietary intervention (sustained reduction in caloric intake relative to ad libitum/baseline)

Aliases: Calorie restriction, CALERIE (trial name -- the trial, not synonymous with the general intervention)

Relationship to mTOR: Reduced nutrient/energy availability is upstream of mTORC1 via AMPK activation (energy sensing, see /ampk) and reduced amino-acid/insulin-IGF-1 signaling input (see /igf1-signaling); proposed to lower mTORC1 activity. This dataset does not compile direct human mTORC1 pathway-biomarker data for CR beyond the aging-clock and cardiometabolic endpoints below.

Mechanism summary: Sustained energy-intake reduction. In the CALERIE Phase 2 human trial, participants were ASSIGNED a 25% caloric-restriction target but ACHIEVED a substantially smaller mean reduction in practice -- these two values are stored separately, never conflated.

Regulatory status

Dietary/behavioral intervention; not a drug. No regulatory approval framework applies. No specific 'longevity CR protocol' is endorsed by this site.

Evidence per species / population (5-qualifier claim format)
Human (CALERIE Phase 2 RCT)   Tier 3 · Human biomarker RCT verification: verified_2026-07-11
1. Species / populationHealthy, non-obese adults, CALERIE Phase 2 RCT
2. Exposure, route, scheduleCaloric restriction: ASSIGNED target 25% reduction from baseline intake; ACHIEVED mean reduction approx. 11.9% (assigned and achieved stored as separate values)
3. Comparator & durationAd libitum control diet; 2-year duration
4. Endpoint & numeric resultImproved cardiometabolic markers; DunedinPACE epigenetic pace-of-aging marker reduced by approx. 2-3%; PhenoAge and GrimAge epigenetic clocks showed no significant effect
5. What this study did NOT establishDid NOT test lifespan or mortality. A change in one epigenetic pace-of-aging marker (DunedinPACE) without a corresponding change in two other validated clocks (PhenoAge, GrimAge) does not establish a generalized 'slowed aging' effect, and none of these clocks is a validated lifespan-prediction endpoint in this dataset.
Linked study record: CALERIE Phase 2 primary trial (caloric restriction, 2-year RCT)
Human (CALERIE Phase 2, DunedinPACE sub-analysis)   Tier 3 · Human biomarker RCT verification: verified_2026-07-11
1. Species / populationHealthy, non-obese adults, CALERIE Phase 2 RCT (DunedinPACE epigenetic sub-analysis)
2. Exposure, route, scheduleSame CALERIE Phase 2 exposure: 25% assigned target, ~11.9% mean achieved reduction
3. Comparator & durationAd libitum control diet; 2-year duration
4. Endpoint & numeric resultDunedinPACE (pace-of-aging epigenetic marker) reduced by approximately 2-3% in the CR group relative to control
5. What this study did NOT establishDid not test lifespan. DunedinPACE is one of several epigenetic clocks; PhenoAge and GrimAge, tested in the same trial, showed no significant CR effect, so this single-marker result should not be generalized to 'all aging clocks' or to lifespan.
Linked study record: CALERIE Phase 2 DunedinPACE epigenetic sub-analysis
Negative / null / conflicting findings

PhenoAge and GrimAge epigenetic clocks showed no significant CALERIE Phase 2 CR effect, despite a DunedinPACE reduction in the same trial. [study record] verification: verified_2026-07-11

CALERIE Phase 2 tested cardiometabolic and aging-biomarker endpoints only; it did not test lifespan or mortality. [study record] verification: verified_2026-07-11

Safety

Safety notes

As a dietary intervention rather than a drug, there is no regulatory drug label. Sustained 25%-target caloric restriction in the CALERIE trial was studied under close clinical and nutritional monitoring; general-population safety and tolerability of self-directed caloric restriction at various levels is not compiled in this dataset and should not be inferred from the supervised trial context.

Source: (not applicable (no drug label; dietary/behavioral intervention)) verification: verified_2026-07-11

Editorial policy: This site publishes no CR percentage-target calculator and no self-directed caloric-restriction protocol guidance.

Data model warning: Caloric restriction is stored with ASSIGNED (target) percentage and ACHIEVED percentage as two separate numeric fields (CALERIE Phase 2: 25% assigned vs ~11.9% mean achieved) -- these must never be silently conflated into a single 'CR level' value.

Funding / conflict of interest

Funding sources and conflict-of-interest disclosures for individual studies are not reproduced here pending primary-source verification; see each linked study record.

Related study records
CALERIE Phase 2 primary trial (caloric restriction, 2-year RCT)
Tier 3 · Human
CALERIE Phase 2 DunedinPACE epigenetic sub-analysis
Tier 3 · Human
Version 0.2.0-mvp · literature search date 2026-07-11 · editorial owner Nabus Research