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-drug complex binds the FRB domain of mTOR within mTORC1 and allosterically inhibits its signaling. The response is ...

no randomized human lifespan endpoint in these studiesanimal lifespan: yes3 evidence rows
Naturally occurring polyamine; autophagy-associated dietary compound

Spermidine

Named primary experiments address EP300 activity and cultured-cell autophagy separately from mouse survival/cardiac cohorts, a rat survival ...

no randomized human lifespan endpoint in these studiesanimal lifespan: mixed experimental findings2 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-drug complex binds the FRB domain of mTOR within mTORC1 and allosterically inhibits its signaling. The response is ...

no randomized human lifespan endpoint in these studiesanimal lifespan: yes2 evidence rows
mTOR inhibitor (rapalog; FKBP12-mediated mTORC1 inhibitor, structurally related to rapamycin/sirolimus with modified pharmacokinetics)

Everolimus

The cited US labels describe FKBP12-mediated mTOR inhibition. The short-course Mannick trials measured vaccine antibody and infection-report...

no randomized human lifespan endpoint in these studiesanimal lifespan: none in dataset2 evidence rows
Investigational ATP-competitive mTOR-pathway inhibitor (BEZ235/dactolisib), distinct from the allosteric rapalogs rapamycin, sirolimus and everolimus

RTB101

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

no randomized human lifespan endpoint in these studiesanimal 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...

no randomized human lifespan endpoint in these studiesanimal 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...

observational mortality associationanimal 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...

no randomized human lifespan endpoint in these studiesanimal lifespan: yes (sex-specific)1 evidence rows
Dietary single-amino-acid restriction (isoleucine only, distinct from combined BCAA restriction)

Isoleucine Restriction

Green et al. 2023 tested 67%isoleucine restriction from6 months in genetically heterogeneous UM-HET3 mice. This is a Lamming-group primary s...

no randomized human lifespan endpoint in these studiesanimal lifespan: sex-dependent isolated-isoleucine result1 evidence rows
Biguanide antidiabetic drug ('mTOR-adjacent' -- not a direct or selective mTOR inhibitor)

Metformin

The cited cell experiments show that metformin can alter mTORC1 signaling through pathways that vary by cell model, including effects indepe...

no randomized human lifespan endpoint in these studiesanimal lifespan: yes (dose-dependent)4 evidence rows
Behavioral/physical-activity intervention (sustained aerobic training)

Aerobic Exercise

The cited acute experiment compared cycling with unilateral leg extensions in six completers. S6K1 Thr389 rose after both modes at 4 hours; ...

observational mortality associationanimal lifespan: none in dataset2 evidence rows
Behavioral/physical-activity intervention (structured resistance/strength training)

Resistance Exercise

The cited acute experiment compared cycling with unilateral leg extensions in six completers. S6K1 Thr389 rose after both modes at 4 hours; ...

observational mortality associationanimal lifespan: none in dataset2 evidence rows
Tier 5 · Mus musculus (UM-HET3, genetically heterogeneous)

NIA Interventions Testing Program (ITP) 2009 rapamycin cohort

Age at death or euthanasia; 90th-percentile survival age and 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: mnemonic discrimination performance on the Mnemonic Similarity Task

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

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

Median age at death or euthanasia; sex- and dose-dependent survival

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

Primary influenza-vaccine geometric-mean-titer ratio; prespecified overall self-reported infection rate, with respiratory-infection rate assessed post hoc

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 cardiometabolic report (2-year RCT; exploratory outcomes)

Cardiometabolic risk markers (2019 publication); methylation algorithms belong to the separate linked2023 analysis

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

Mouse survival; cardiovascular endpoints from separate cohorts

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)

Mouse lifespan; hepatic phospho-mTOR/total-mTOR and circulating BCAA/glucose measurements

Tier 6 · Mus musculus

Combined BCAA restriction and mouse lifespan (Richardson et al., 2021)

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

Mean lifespan, dose-dependent

Tier 8 · Human

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

Muscle/adipose gene expression and mixed-meal metabolic markers; not hard disease, physical function or lifespan outcomes

Tier 2 · Human

MASTERS trial (metformin + resistance exercise interaction)

Muscle mass / strength gains from resistance training

Tier 10 · Human

TAME (Targeting Aging with Metformin): published trial design

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)

The TSC complex contains TSC1, TSC2, and TBC1D7. Its TSC2 subunit supplies GTPase-activating protein (GAP) activity toward Rheb, converting ...

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 senses cellular energy stress and can inhibit mTORC1 through regulation of TSC2 and direct phosphorylation of Raptor. These are model-d...

Downstream effector / autophagy-initiation kinase

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

ULK1 participates in autophagy initiation. In the cited cell experiments, mTORC1 phosphorylated ULK1 at Ser757, disrupting its interaction w...

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 participates upstream of mTORC1 through regulation of the TSC/Rheb branch and is also regulated by mTORC2-associated phosphorylation. Se...

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. 1 intervention page — Spermidine — carries an existing Amazon affiliate search link. Retail products are not established as equivalent to the experimental materials. Prescription and investigational compounds carry no purchase link; dietary and exercise exposures are not linked products. There is no sponsored content and no named/fabricated author — it is published under the Nabus AS editorial identity. See the affiliate disclosure.