// Evidence Grader
Every claim, graded
55 graded claims across the course. Use grades to calibrate your confidence — and your patients'.
A
Regular aerobic + resistance exercise reduces all-cause mortality
Among the most robust findings in epidemiology and RCTs.
Why Longevity, Why Now
A
Smoking cessation at any age extends life expectancy
Quitting before 40 avoids ~90% of excess mortality risk.
Why Longevity, Why Now
C
Caloric restriction extends lifespan in humans
CALERIE-2 showed metabolic benefits; lifespan unproven.
Why Longevity, Why Now
D
NMN/NR supplements slow human aging
Raise NAD+; no convincing healthspan endpoints.
Why Longevity, Why Now
E
Resveratrol mimics caloric restriction in humans
Hyped from yeast/mouse data; human trials largely null.
Why Longevity, Why Now
F
A young person's blood transfusion reverses aging
No controlled human evidence; FDA warning issued 2019.
Why Longevity, Why Now
A
Senescent cell burden increases with age in human tissue
Replicated across multiple tissue atlases.
The Hallmarks of Aging
B
Epigenetic clocks estimate biological age
Strong correlations; causal status and reversibility debated.
The Hallmarks of Aging
B
Inflammaging contributes to multimorbidity
Robust mechanistic and observational support.
The Hallmarks of Aging
D
All 12 hallmarks are independently druggable
Many lack validated human-grade modulators.
The Hallmarks of Aging
A
Higher cardiorespiratory fitness is associated with lower all-cause mortality
Dose-dependent across multiple large cohorts.
Exercise — The Most Powerful Geroprotector
A
Resistance training reduces all-cause mortality independent of cardio
Meta-analyses show 10–17% reduction.
Exercise — The Most Powerful Geroprotector
C
Zone 2 specifically increases mitochondrial density more than HIIT
Plausible mechanism; head-to-head human evidence limited.
Exercise — The Most Powerful Geroprotector
E
Marathon training shortens life expectancy
Net effect is favorable; J-curve concerns are at extreme ultra-endurance levels.
Exercise — The Most Powerful Geroprotector
A
Mediterranean diet reduces major cardiovascular events
PREDIMED replication and meta-analyses.
Nutrition, Fasting & Caloric Restriction
B
Higher protein intake (1.2–1.6 g/kg) preserves lean mass in older adults
Consistent across PROT-AGE and ESPEN guidelines.
Nutrition, Fasting & Caloric Restriction
C
Time-restricted eating uniquely improves metabolism beyond calorie reduction
Most isocaloric trials show no advantage.
Nutrition, Fasting & Caloric Restriction
C
Caloric restriction will extend human lifespan
Plausible; biomarker support; mortality unproven.
Nutrition, Fasting & Caloric Restriction
E
Seed oils cause inflammation and accelerate aging
Contradicted by RCT and prospective evidence.
Nutrition, Fasting & Caloric Restriction
B
Chronic short sleep (<6h) increases all-cause mortality risk
Confounded by reverse causation but consistent.
Sleep, Stress & Circadian Health
A
Untreated OSA increases CV mortality
Strong observational and mechanistic data.
Sleep, Stress & Circadian Health
A
CBT-I outperforms sleeping pills for chronic insomnia
First-line per AASM guidelines.
Sleep, Stress & Circadian Health
F
Mouth taping cures sleep apnea
No evidence; can be harmful in OSA.
Sleep, Stress & Circadian Health
D
Blue-blocking glasses meaningfully improve sleep
Modest signal; ambient light reduction matters more.
Sleep, Stress & Circadian Health
B
ApoB outperforms LDL-C for CV risk prediction
Increasingly endorsed by lipid guidelines.
Biomarkers & Biological Age Testing
A
Lp(a) is genetically determined and additive to other risk
Robust genetic and epidemiologic evidence.
Biomarkers & Biological Age Testing
A
Grip strength predicts all-cause mortality
Confirmed across PURE and UK Biobank.
Biomarkers & Biological Age Testing
D
Consumer epigenetic age is reproducible week-to-week
Test-retest variability often exceeds yearly drift.
Biomarkers & Biological Age Testing
E
A single biological age number captures aging
Aging is multi-dimensional; no single metric suffices.
Biomarkers & Biological Age Testing
A
Rapamycin extends lifespan in mice
ITP-replicated across sexes and start ages.
Pharmacology of Healthspan
C
Metformin reduces all-cause mortality in non-diabetics
TAME pending; observational signals mixed.
Pharmacology of Healthspan
A
GLP-1 agonists reduce CV mortality in T2D and obesity
SUSTAIN-6, SELECT, STEP trials.
Pharmacology of Healthspan
D
Off-label rapamycin extends human healthspan
Plausible; no RCT evidence yet.
Pharmacology of Healthspan
F
Compounded peptide stacks are FDA-approved longevity therapies
FDA has issued explicit warnings on compounded peptides.
Pharmacology of Healthspan
B
Cyclic OSKM expression rejuvenates tissues in mice
Replicated; safety in long-term and human applicability unclear.
Frontier Science & Future Therapeutics
B
Heterochronic parabiosis improves multiple aging markers in mice
Robust preclinical effect; mechanism debated.
Frontier Science & Future Therapeutics
F
Young plasma transfusions are an FDA-approved anti-aging therapy
FDA explicitly warned against this in 2019.
Frontier Science & Future Therapeutics
F
Telomerase gene therapy is safe and ready for humans
Cancer risk and translational gaps remain substantial.
Frontier Science & Future Therapeutics
B
Inducing non-mutagenic DSBs in mice (ICE model) accelerates epigenetic and physiological aging
Yang et al. Cell 2023; striking result, awaiting independent replication at scale.
The Information Theory of Aging — Sinclair Lab Deep Dive
B
AAV2-OSK restores vision and youthful methylation patterns in aged/injured mouse retina
Lu et al. Nature 2020; replicated in part by other labs; foundation of Life Bio's clinical program.
The Information Theory of Aging — Sinclair Lab Deep Dive
C
Aging involves loss of epigenetic information, not just DNA damage
Increasingly accepted as a mechanism, but 'cause vs consequence' is actively debated (Gladyshev, Brunet).
The Information Theory of Aging — Sinclair Lab Deep Dive
B
DNA methylation clocks (Horvath, GrimAge, DunedinPACE) measure biological age
Strong correlations with mortality and morbidity; causal interpretation and intervention-responsiveness still being validated.
The Information Theory of Aging — Sinclair Lab Deep Dive
D
Partial reprogramming with OSK can be safely used in humans today
First-in-human trials for NAION are only just starting; whole-body use remains preclinical.
The Information Theory of Aging — Sinclair Lab Deep Dive
D
NMN supplementation extends human healthspan or lifespan
Raises NAD+ in humans; no convincing hard-endpoint RCT data; FDA NDI status itself contested.
The Information Theory of Aging — Sinclair Lab Deep Dive
E
Resveratrol activates SIRT1 and mimics caloric restriction in humans
The original Sirtris/GSK program failed; assay artifacts (fluorescent peptide) explained much of the SIRT1 'activation' signal.
The Information Theory of Aging — Sinclair Lab Deep Dive
D
Consumer 'biological age' tests can guide clinical decisions
Useful for research; precision, intervention-responsiveness, and clinical actionability are not yet established.
The Information Theory of Aging — Sinclair Lab Deep Dive
F
Sinclair's lab has 'cured aging' or 'reversed aging in humans'
No published human aging-reversal data from this program; media framing routinely overstates mouse results.
The Information Theory of Aging — Sinclair Lab Deep Dive
C
Aging consists of a finite, enumerable set of damage categories that are in principle repairable
Conceptually influential and partially validated (senolytics, mtDNA gene therapy); not a settled framework.
Aubrey de Grey & SENS — Engineering Negligible Senescence
B
Senescent cell clearance improves healthspan in mice
Replicated across multiple labs; SENS's ApoptoSENS prefigured the senolytic field.
Aubrey de Grey & SENS — Engineering Negligible Senescence
C
Allotopic expression can rescue mtDNA mutations in human cells
ATP6/ATP8 demonstrated; full 13-gene rescue not achieved.
Aubrey de Grey & SENS — Engineering Negligible Senescence
B
Glucosepane is the dominant long-lived crosslink in human ECM
Spiegel-lab synthesis enabled detection; biology supports the claim; therapeutic breakers still preclinical.
Aubrey de Grey & SENS — Engineering Negligible Senescence
E
WILT (deleting telomerase from all somatic cells with periodic stem-cell replenishment) is a credible near-term anticancer strategy
Internally consistent within SENS but operationally and immunologically implausible on current technology.
Aubrey de Grey & SENS — Engineering Negligible Senescence
E
Longevity Escape Velocity will be reached within 15–20 years with ~50% probability
Personal forecast; not a consensus or evidence-based projection.
Aubrey de Grey & SENS — Engineering Negligible Senescence
F
The first person to live to 1000 is probably already alive
Rhetorical claim with no empirical basis; widely repeated, not scientifically supported.
Aubrey de Grey & SENS — Engineering Negligible Senescence
D
Robust Mouse Rejuvenation has produced large lifespan extension in old mice via combination therapy
Preliminary, conference-stage; awaiting peer-reviewed full datasets.
Aubrey de Grey & SENS — Engineering Negligible Senescence