Twitter Thread about mice experiments where controls don't live for 900 days

#1

https://twitter.com/_sviridov_/status/1777332915447169047

(5/6) Now, let’s discuss the paper I mentioned earlier: https://biorxiv.org/content/10.1101/2023.10.08.561459v1.full…. The authors demonstrated that short-lived controls in lifespan experiments can skew the results and exaggerate the effects of interventions. In other words, the longer the control group lives, the smaller the effect of the intervention. With long-living control groups, the intervention might even have a negative effect, despite showing positive outcomes with short-living controls. You can even see it back in the CR study I mentioned before. As we go from short-living to long-living breeds, the positive impact of CR becomes increasingly scarce, and on the rare occasions it remains positive, its magnitude is getting smaller & smaller. The authors introduced a ‘900-day rule’ - mouse longevity intervention should only be considered with high confidence when control lifespans are close to 900 days or if the final lifespan of the treated group is considerably above 900 days. And then, they analyzed the results of ITP with it. And here’s the kicker: “When data from all three ITP cohorts was pooled, no interventions met our 900-day criteria except rapamycin and rapamycin combinations in female mice”. Yikes!

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#2

This is important. All of us here must not fool ourselves into thinking these chemicals we take will make all the difference because “science” says so. the chemicals can only be icing on the cake.

Here’s my plan

Job#1 — I’m working to get my lifestyle in a good spot: physical activity (cardio, strength, mobility), natural (non drug aided) sleep, real food (non supplement) diet composition, social connection. If this alone doesn’t achieve health goals, add in targeted chemicals and food-like supplements to make additional corrections.

Not 100 things that should help (because a study showed it did and everybody thinks so) but a few things that I used and saw improvement in my health. i think drugs and supplements are useful short term aids to quickly move in the right direction but not a long term solution. The main problem is we don’t really know enough.

I think @ConquerAging has the right approach:

  1. Focus on lifestyle. Track and adjust.

  2. Get physical biomarkers in a good spot: RHR, BP, body composition, bone density (and quality). Lowest ACM is a fine target. Subjective markers like joint pain, skin aging, etc are also useful.

  3. Get blood markers in a good spot: HbA1c, HOMA-ir, apoB, sex hormones, immune / inflammation markers, iron status, kidney function, liver function, etc

  4. Epigenetic age tests are a sideshow for giggles. Organ age testing (proteomics) might be useful as it is actionable.

  5. Rapamycin is the only chemical that I believe will make an important difference that I cannot get via lifestyle. I wait for more data on other chemicals. My apoB and blood sugar meds are long term “temporary” as I search for a better way.

Track and adjust. Lifestyle is the cake. Added chemicals are the sprinkles on the icing on the cake.

Here’s a related thread in Twitter : https://x.com/_sviridov_/status/1777332900297347220?s=46&t=g51H5gL_rX6JIVg_7VgkQg

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#3

Much that I linked to the original post on Twitter, I do think interventions other than lifestyle have a material effect. I continue working on this.

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#4

It is good to have people trying new things to discover what will work. I’m just saying don’t count on it. Rapamycin is the one exception so far, in my opinion.

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