v1.2 · Apr 2026 · Organ systems, brain-first, global evidence

A longevity operating system,
not a podcast transcript.

Every intervention ranked by the strength of its human evidence, its expected effect on healthspan, the cost, the inconvenience, and the organs it actually moves. Brain, heart, kidneys, liver, bone, muscle, immune, eyes — held to the same standard. Sauna, GLP-1s, resistance training, SGLT2, sleep, omega-3, hearing aids, rapamycin, peptides, nootropics — all on the same scoreboard.

See the ranking Skip to the reality check
Interventions
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Real human outcomes
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Biomarker-only
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Mostly lore
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§ Brain-first · New in v1.2

If you do one thing for your brain, make it one of these.

The Lancet Dementia Commission (2024) estimates ~45% of dementia is preventable by addressing 14 modifiable risk factors. Below: every intervention in the OS with at least moderate human evidence for cognition or dementia, scored 0–3.

Scoring: 3 = hard outcome data (dementia incidence, cognitive decline slowed in RCT). 2 = moderate human data (cohort or biomarker + mechanism). Click any row for the full card.

2026 Briefing

What the newest evidence actually says.

Nature Aging · March 2026

Dietary restriction is the most mechanism-rich longevity lever — and still biomarker-only in humans.

In the definitive 2026 review, Schmauck-Medina and Fang synthesize three decades of dietary-restriction (DR) science: DR extends lifespan across nearly every species tested, operating through autophagy, AMPK, mTORC1, NAD+, FGF21, and SIRTs. In humans, CALERIE showed ~12% caloric restriction for two years slowed DunedinPACE by 2–3% — an effect that, if it translates, maps to roughly 10–15% lower mortality risk, comparable to smoking cessation. But individual variation is enormous and no hard-outcome trial exists yet.

Centenarian resilience · 2026

Cognitively healthy centenarians are genetically protected against Alzheimer's — not just lucky.

A five-cohort analysis shows centenarians across the US, Europe, and Asia carry a higher Alzheimer's polygenic protective score than controls — beyond APOE. Protection increases with age: supercentenarians (≥110) carry the most protective alleles. Complementary work on centenarian microglia finds they overexpress neprilysin, clearing amyloid 1.5–2× faster than young adult microglia. Implication: reaching 100 cognitively intact is a resilience phenotype, not an absence-of-risk one.

§01 / Ranked Interventions

The operating system.

Ranked by a composite of evidence strength, effect size, and biomarker coverage — penalized by cost and inconvenience. Filter to see where you want to spend your time.

Verdict
Category
Evidence from
# Intervention Verdict Evidence Effect Cost / mo Effort Biomarkers Composite
§ Organ coverage · New in v1.2

Every intervention × every organ.

How many strong-evidence interventions actually target each organ. Cells score 0–3: blank = none, 1 = plausible, 2 = moderate human data, 3 = strong human outcomes.

§02 / Don't-Fool-Yourself Mode

What actually has human outcome data — and what doesn't.

The hierarchy: REAL interventions have hard human outcomes (mortality, disease, function). MIXED have only biomarker or short-term RCTs. LORE is mostly preclinical, anecdotal, or podcast culture. An intervention can be worth doing at any level — but you should know which shelf you're buying from.

§03 / Intervention Detail

Click any intervention for the full card.

§04 / Default Protocol

If you had to pick a starting stack,
start where the outcomes are.

Tier 1 · Do these first
  • Resistance training — 2–3×/week, ~60 min/week total
  • Sleep 7–7.5h, consistent schedule, screen for OSA if loud snorer
  • VO₂max work — 150+ min/week moderate or 75 min vigorous
  • Creatine 3–5 g/day (kidney-caveat: check)
  • Omega-3 EPA/DHA 1–2.5 g/day — brain, heart, eyes
  • Hearing aids if hearing is impaired — highest-leverage brain intervention in existence

Each has a mortality or dementia signal in humans. Nothing else on this site has a stronger case.

Tier 2 · Add if they fit your life
  • Sauna — 4+ sessions/week, ≥19 min (observational but huge brain+heart signal)
  • MIND-style diet — leafy greens daily, berries, fish, olive oil
  • Time-restricted eating — 8–10h window, front-loaded
  • Mild caloric restriction — only if you're not already lean/sarcopenic
  • Vitamin D + K2 — only if 25-OH-D is low

Solid biomarker evidence, outcomes still coming.

Tier 3 · Consider with a physician
  • GLP-1s (semaglutide, tirzepatide) — when BMI/metabolic risk warrants
  • SGLT2 inhibitors — now first-line for CKD ± diabetes, heart failure protection
  • Colchicine 0.5 mg — for established coronary disease
  • Resmetirom — for biopsy-confirmed MASH with fibrosis
  • B-vitamins — only if homocysteine elevated
  • Rapamycin — low-dose intermittent, adults 50+, off-label
  • Metformin — stronger case in metabolic risk / older adults
  • Thymosin α-1 — narrow indications (immune recovery, hepatitis)
  • AREDS2 — only for intermediate AMD, not general eye health
  • GHK-Cu cream — topical only, skin outcomes

GLP-1s have the strongest hard-outcome data of any Rx here. Mouse-to-human longevity translation for the rest is still an open bet.

Tier 4 · Treat as entertainment, not a plan
  • NMN, NR — raise NAD+, unclear if that matters
  • Epitalon — single Russian group, implausible effect sizes
  • Cold plunge beyond short cold showers
  • BPC-157, CJC/Ipamorelin — near-zero human outcome data, FDA-restricted
  • Lion's Mane, Bacopa, most nootropic stacks

May feel good. Probably won't move your 10-year mortality curve. Some have real downside risk.

§05 / Key Papers

The primary sources this is built on.