12
Interventions
21
Study records
12
Pathway reference pages
1
Affiliate link
mTOR inhibitor (macrolide; direct FKBP12-mediated mTORC1 inhibitor)

Rapamycin

Binds FKBP12; the FKBP12-rapamycin complex binds the FRB domain of mTOR within mTORC1, allosterically inhibiting mTORC1 kinase output toward...

human lifespan evidence: noneanimal lifespan: yes3 evidence rows
Naturally occurring polyamine; autophagy-associated dietary compound

Spermidine

Associated with induction of autophagic flux and cardiovascular protection in animal models; proposed mechanisms include EP300 inhibition an...

human lifespan evidence: noneanimal lifespan: mixed (species-dependent)2 evidence rows
mTOR inhibitor (macrolide; direct FKBP12-mediated mTORC1 inhibitor) -- FDA generic/INN drug name for the same molecular entity as rapamycin

Sirolimus

Binds FKBP12; the FKBP12-sirolimus complex binds the FRB domain of mTOR within mTORC1, allosterically inhibiting mTORC1 kinase output toward...

human lifespan evidence: noneanimal lifespan: yes2 evidence rows
mTOR inhibitor (rapalog; FKBP12-mediated mTORC1 inhibitor, structurally related to rapamycin/sirolimus with modified pharmacokinetics)

Everolimus

Binds FKBP12; the complex inhibits mTORC1 kinase output, reducing S6K1/4E-BP1 signaling. In Mannick et al.'s low-dose human trials, short-co...

human lifespan evidence: noneanimal lifespan: none in dataset2 evidence rows
Investigational TORC1 inhibitor (rapalog-class small molecule, distinct chemical entity from rapamycin/sirolimus/everolimus)

RTB101

Reported as a TORC1 inhibitor tested for respiratory-illness-related endpoints in older adults; mechanism-level detail beyond 'TORC1 inhibit...

human lifespan evidence: noneanimal lifespan: none in dataset2 evidence rows
Dietary intervention (sustained reduction in caloric intake relative to ad libitum/baseline)

Caloric Restriction (CR)

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

human lifespan evidence: noneanimal lifespan: not quantified2 evidence rows
Dietary macronutrient-ratio intervention (total dietary protein, independent of any single amino acid)

Protein Restriction

Reduction of total dietary protein (as opposed to a single amino acid or amino-acid class). Studied in animals via the Solon-Biet nutritiona...

no human lifespan RCT (observational)animal lifespan: yes2 evidence rows
Dietary amino-acid-class restriction (leucine + isoleucine + valine, restricted together as the branched-chain amino acid class)

BCAA Restriction (Branched-Chain Amino Acid Restriction)

Combined reduction of all three branched-chain amino acids (leucine, isoleucine, valine) in the diet, studied for sex-specific lifespan effe...

human lifespan evidence: noneanimal lifespan: yes (sex-specific)1 evidence rows
Dietary single-amino-acid restriction (isoleucine only, distinct from combined BCAA restriction)

Isoleucine Restriction

Isoleucine-specific dietary reduction, studied within the nutritional-geometry research tradition associated with the Solon-Biet/Simpson/Rau...

human lifespan evidence: noneanimal lifespan: not quantified1 evidence rows
Biguanide antidiabetic drug ('mTOR-adjacent' -- not a direct or selective mTOR inhibitor)

Metformin

Activates AMPK and inhibits mitochondrial complex I; AMPK activation is one of several inputs that can inhibit mTORC1 via TSC2, but this is ...

human lifespan evidence: noneanimal lifespan: yes (dose-dependent)4 evidence rows
Behavioral/physical-activity intervention (sustained aerobic training)

Aerobic Exercise

A single bout of aerobic exercise acutely activates mTORC1 signaling in skeletal muscle (e.g. increased p-S6K1 Thr389); chronic training sep...

no human lifespan RCT (observational)animal lifespan: none in dataset2 evidence rows
Behavioral/physical-activity intervention (structured resistance/strength training)

Resistance Exercise

Mechanical loading during resistance training acutely activates mTORC1 signaling in skeletal muscle, promoting the protein-synthesis respons...

no human lifespan RCT (observational)animal lifespan: none in dataset2 evidence rows
Tier 5 · Mus musculus (UM-HET3, genetically heterogeneous)

NIA Interventions Testing Program (ITP) 2009 rapamycin cohort

Age at 90% mortality (90th-percentile lifespan); median lifespan

Tier 2 · Human

PEARL trial (rapamycin, 48-week RCT)

Primary: visceral adipose tissue (fat) change

Tier 2 · Human

SmartAge trial (spermidine via wheat germ extract, 12-month RCT)

Primary: cognitive composite score change

Tier 5 · Mus musculus (UM-HET3, genetically heterogeneous)

NIA ITP rapamycin dose-response cohort (42 ppm arm)

Median lifespan, dose-response arm

Tier 2 · Human

Mannick et al. 2014 low-dose everolimus / influenza vaccine response trial

Influenza vaccine antibody response

Tier 2 · Human

Mannick Phase 2a follow-on TORC1-inhibitor immune trial

Immune-function / infection-related endpoints (follow-on to the 2014 vaccine-response finding)

Tier 2 · Human

RTB101 Phase 2b respiratory-illness trial

Laboratory-confirmed respiratory tract illness

Tier 2 · Human

RTB101 Phase 3 respiratory-illness program (1024 participants)

Primary respiratory illness endpoint

Tier 3 · Human

CALERIE Phase 2 primary trial (caloric restriction, 2-year RCT)

Cardiometabolic risk markers; epigenetic aging-pace markers (see calerie-dunedinpace for the DunedinPACE-specific record)

Tier 3 · Human

CALERIE Phase 2 DunedinPACE epigenetic sub-analysis

DunedinPACE (pace-of-aging epigenetic marker)

Tier 6 · Mus musculus

Eisenberg spermidine mouse drinking-water lifespan study

Median lifespan; cardiovascular markers

Tier 6 · Rattus norvegicus

Conflicting rat spermidine drinking-water study (non-replication)

Median lifespan

Tier 6 · Mus musculus

Solon-Biet nutritional geometric framework (25-diet mouse study)

Median lifespan; circulating IGF-1

Tier 6 · Mus musculus

BCAA / isoleucine restriction mouse lifespan study (sex-specific)

Median lifespan, by sex

Tier 4 · Human

Levine et al. dietary protein observational cohort (n=6381)

All-cause mortality

Tier 8 · Human

Acute exercise mTORC1 mechanistic crossover study (untrained men)

mTORC1 pathway activation (e.g. p-S6K1 Thr389) in skeletal muscle

Tier 4 · Human

Physical activity and all-cause mortality meta-analysis

All-cause mortality

Tier 6 · Mus musculus

Dietary metformin mouse lifespan dose-response study

Median lifespan, dose-dependent

Tier 8 · Human

MILES trial (metformin, short-term mechanistic study in older adults)

Mechanistic/molecular endpoints (e.g. gene-expression/pathway signatures)

Tier 2 · Human

MASTERS trial (metformin + resistance exercise interaction)

Muscle mass / strength gains from resistance training

Tier 10 · Human

TAME (Targeting Aging with Metformin) trial -- protocol/registration, no results

Planned aging-related composite clinical endpoint

Biology reference · complex comparison

mTORC1 vs mTORC2

Mechanistic Target of Rapamycin (mTOR) assembles into two distinct multiprotein complexes, mTORC1 and mTORC2, distinguished by scaffold prot...

Upstream regulator (GTPase-activating complex)

TSC1/TSC2 (Tuberous Sclerosis Complex 1/2)

TSC1/TSC2 form a heterodimeric GTPase-activating protein (GAP) complex that converts Rheb-GTP to its inactive Rheb-GDP form, thereby suppres...

Upstream regulator (small GTPase)

Rheb (Ras homolog enriched in brain)

Rheb is a small GTPase that, in its GTP-bound (active) form, directly binds and activates mTORC1 at the lysosomal membrane. Its activity is ...

Upstream regulator (amino-acid sensing, GTPase heterodimer + scaffold)

Rag GTPases / Ragulator complex

The Rag GTPase heterodimers, anchored to the lysosomal membrane by the Ragulator scaffold complex, sense amino-acid sufficiency and recruit ...

Upstream regulator (energy-sensing kinase)

AMPK (AMP-activated protein kinase)

AMPK is the cell's principal energy-status sensor, activated by a rising AMP:ATP or ADP:ATP ratio (low cellular energy). Once active, AMPK i...

Downstream effector / autophagy-initiation kinase

ULK1 (Unc-51-like autophagy-activating kinase 1)

ULK1 is a serine/threonine kinase that initiates autophagosome formation. Active mTORC1 phosphorylates ULK1 at inhibitory sites, SUPPRESSING...

Downstream effector / protein-synthesis kinase

S6K1 (p70 ribosomal protein S6 kinase 1)

S6K1 is directly phosphorylated by mTORC1 at Thr389, the canonical assay marker for mTORC1 activity used throughout this dataset (p-S6K1 Thr...

Downstream effector / translation-initiation regulator

4E-BP1 (eIF4E-binding protein 1)

4E-BP1 normally binds and sequesters eIF4E, blocking cap-dependent translation initiation. Active mTORC1 phosphorylates 4E-BP1 at multiple s...

Downstream effector / lysosomal-autophagy transcription factor

TFEB (Transcription Factor EB)

TFEB is the master transcriptional regulator of lysosomal biogenesis and autophagy genes. Active mTORC1 phosphorylates TFEB, retaining it in...

Upstream regulator AND mTORC2 substrate (dual role)

AKT (Protein Kinase B)

AKT plays a dual role in this pathway map. As part of the insulin/IGF-1-PI3K-AKT axis, active AKT phosphorylates and INHIBITS TSC2, relievin...

Upstream regulator (growth-factor signaling axis)

IGF-1 Signaling (Insulin/IGF-1 -> PI3K -> AKT axis)

Insulin and IGF-1 binding to their receptors activates PI3K, which activates AKT, which inhibits TSC1/2, which activates Rheb, which activat...

Process (dynamic, not a single molecule)

Autophagic Flux

CORE EDITORIAL POINT: autophagic flux is the RATE of the complete autophagy process -- autophagosome formation, cargo sequestration, fusion ...

Tier 1Human lifespan / clinical RCT
Tier 2Human clinical/functional RCT
Tier 3Human biomarker RCT
Tier 4Prospective human observational
Tier 5Replicated animal lifespan
Tier 6Single-lab animal lifespan
Tier 7Animal healthspan
Tier 8Human acute mechanistic
Tier 9Animal/cell mechanism
Tier 10Hypothesis / unreplicated

What this site is

mTORiX is a claim–study–outcome graph, not a longevity-advice essay. Every quantitative claim carries five visible qualifiers: species/population; exposure, route, and schedule; comparator and duration; endpoint and numeric result; and what the study did NOT establish. Evidence tiers are shown, not collapsed into a single score. One page — Spermidine, the only compound here that is sold over the counter at all — carries an affiliate link to the material the studies used; every prescription and investigational compound carries none, and the dietary and exercise interventions are not products. There is no sponsored content and no named/fabricated author — it is published under the Nabus Research editorial identity. See the affiliate disclosure.