An Evidence-Based Framework for Longevity

#1

This post outlines a practical, three-tiered framework for prioritizing longevity interventions based on the strength of scientific evidence.

Tier 1: Highest Evidence (Proven in Human Trials) The foundation of any longevity strategy should be interventions proven to extend lifespan or reduce all-cause mortality in human randomized controlled trials. These include:

  • Sustained weight loss, achieved through lifestyle changes or, when necessary, medication.
  • Cardiovascular risk reduction through LDL cholesterol lowering (especially with statins) and intensive blood-pressure control.
  • Comprehensive prevention via “polypill” strategies.
  • Testosterone replacement therapy (TRT) for men with clinically low levels. An equivalent strategy for women.
  • Annual flu vaccination.
  • Modest benefits from supplementation with multivitamins, vitamin D, and EPA-rich fish oil.

Tier 2: Strong Associational & Preclinical Evidence This tier includes practices with strong positive associations in human observational studies and/or proven lifespan benefits in animal models.

  • Lifestyle: Regular exercise, a Mediterranean-style diet, and social well-being.
  • Diet & Supplements: Coffee, green tea (EGCG), cocoa, garlic, fiber, glucosamine, and natto (for spermidine and vitamin K2).
  • Pharmaceuticals: Aspirin (data remains mixed).

Tier 3: Emerging & Experimental Interventions These options have shown promise in animal models and have preliminary signals in human studies but require more research. They represent the cutting edge of longevity science.

  • Dietary Strategies: Calorie restriction, one-meal-a-day (OMAD), ketogenic, or lower-carbohydrate diets.
  • Pharmaceuticals & Supplements: Rapamycin, metformin, acarbose, canagliflozin, pioglitazone, taurine, spermidine, creatine, glycine, glycine+NAC, AKG, astaxanthin, curcumin, resveratrol, grape-seed extract, vitamin C, icariin, Glylo, and Protandim.
  • Controversial: NAD+ boosters and fisetin.

Guiding Principles Regardless of the tier, always work with a physician to guide your choices and treat any abnormal biomarkers. Track your personal responses (N=1 analysis), and remember that interventions improving quality of life can be valuable even without proven lifespan benefits. De-prioritize interventions based solely on mechanistic theories until stronger evidence is available.

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#2

A nice list of strategies but youre splitting seems arbitrary. You have fish oil in top tier above exercise, caloric restrictions and arcabose? @assdx would not approve :wink:

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#3

Hey thanks for the feedback! The causal evidence that exercise reduces all cause mortality is weaker than the causal evidence that fish oil reduces all cause mortality. Anyone who’s saying otherwise is making an extrapolation not quite supported by the degree of evidence. That’s why fish oil is in the best tier, but exercise isn’t.

  • Fish oil: Trend towards 3% reduced all-cause mortality (RR = 0.97, 95% CI = 0.94–1.01). 7%-8% reduced risk of CVD mortality (RR = 0.92, 95% CI = 0.87–0.98). More significant mortality reduction with higher dose and EPA-rich omega-3. (ref, ref)
  • Exercise: Did not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants (ref). Cancer is one exception where exercise was causatively shown to improve survival outcomes (ref).
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