The Impact of Short-lived controls on the Interpretation of Lifespan Experiments and Progress in Geroscience

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Authors: @Aging_Scientist @BarardoD @mkaeberlein@BKennedy_aging

”Using this “900-day rule” we identified several candidate interventions from the literature that merit follow-up studies…”

Interesting Points:

Rapamycin, Rapamycin-combos (Rapamycin+Metformin) and telomerase activation appear to be the only things that truly extend lifespan in long-lived strains

Longer-lived strains within species respond less favorably to caloric restriction (CR)

Impact of Short-Lived Controls.pdf (734.3 KB)

Thus, we propose the “900-day rule” for mouse lifespan experiments, which is easy to remember and sufficiently accurate to be useful to editors, reviewers, scientists and lay readers alike. Most healthy inbred or hybrid strains should have a median lifespan of close to 900 days (± 50 days). Since the normative lifespans we presented here are likely a lower bound for the true strain-specific lifespan of these animals, due to husbandry issues, we believe that C57BL/6, UM-HET3 and some other strains are well capable of such lifespans (Table S7). Based on the 900-day rule we define treatments that extend the lifespan of short-lived cohorts as “longevity normalizing”, whereas those that work in long-lived cohorts are “longevity-extending”.

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Based upon my understanding of this article, this article states that most longevity interventions will bring short-lived or unhealthy animals up to par with normal healthy animals. This is great for those who are unhealthy or genetically disadvantage longevity-wise. However, they may not provide benefits to healthy individuals like @Agetron or @desertshores

The only interventions that truly extend lifespan across the board based on current information are Rapamycin, Rapamycin Combos (Rapa+ Met or Rapa+Acarbose), and telomerase activation.

*There also may be interventions that close the lifespan gap between males and females, and these are primarily the interventions that have been shown to primarily benefit males.

@RapAdmin What can we do to activate telomerase safely? Isn’t it tied to cancer activation?

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I’ve not heard of any well-validated ways to activate telomerase, or lengthen telomeres. There have been supplements marketed to do this, but no good studies that convince the scientists that they will make a difference in lifespan.

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Same here.

I guess the only real silver bullet we have against aging right now for everyone is Rapamycin + (Metformin and/or Acarbose).

The rest will just help us males live as long as females (which is great in and of itself!)

At least this will help me get rid of some things out of my current stack.

We really need a new breakthrough.

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Even for Rapamycin, David Sabatini said (https://www.youtube.com/watch?v=wHbEYwQbIh8) that he is not convinced that it has any longevity benefits for those individuals who are healthy, eat well, exercise regularly and do some fasting (that’s why he is not taking it)
He also referred to the longevity effects in mice studies as unconvincing as these animals lead a depressing life in small cages…
I’m on the fence at this point, waiting to see more “evidence” and hoping we’ll get some biomarkers to track positive “progress”… rather than the current tracking of side-effects/negatives to minimise.
In the meantime i’m trying to come up with a “fasting protocol” to intermittantly inhibit mTor, currently trying 40hour fasts (dinner day0 - Lunch day2) twice a month.

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Chris: This is great for those who are unhealthy or genetically disadvantage longevity-wise. However, they may not provide benefits to healthy individuals like @Agetron or @desertshores.

I think you’ve forgotten my former dad bod!

Got my most recent TruMe Methylation results this week.

I am biologically 12 years younger then my chronological 65 and 1/2 years.

The CEO a Ph.D. researcher finds my age difference extremely unusual. As she tells me, my test is not wrong.

Pretty sure its the rapamycin.

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Paraphrasing a popular cigarette slogan:

@Agetron - You’ve come a long way, Agey!

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@Agetron Dude! Why are you smiling in this photo? Nice recovery, as I have said before.

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Fat, oblivious and happy.

Having just eaten a bag of chips with dip. Washed down with a liter of Pepsi.

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Holy moly! I’d never seen it before. Congratulations AT! You clearly really worked at it, in addition to whatever rapa and T may have done for you.

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But… does no one mention deprenyl??

Where does deprenyl come into this?

I would challenge @agetron on weight loss (having gone from 130kg to 85kg in under a year). I must admit I am messing around a bit at the moment, but I am trying to get under 80kg whilst continuning to do chinups with an extra 10kg. Interestingly I concluded earlier today that oddly enough I was calcium deficient. Then a few hours later I got a hair test result which said inter alia that I was calcium deficient.

Inter alia it also said that vitamin B5 (which includes pantethine I would think) has a tendency to cause copper deficiency. Something to note.

There was data on deprenyl extending life in dogs, no?

Yes - reasonably good data in dogs: Deprenyl - Anti-Aging Drug Proven Effective in Dogs

I think the key takeaway here is that there are a lot of drugs, treatments and supplements that are good for you, but they will only take you up to the maximum lifespan for a species. For us, that’d be 122.

Nothing can take us beyond that (according to this paper) except Rapamycin, Rapamycin combos or telomerase activators. Not even CR.

BUT, if you could take your lifespan from 90 to 122, that’s still a lot! So things like deprenyl come into play in this category.

IMHO, if you are taking Rapamycin plus a good stack of supplements (Like taurine, glycine, NAC, etc…) you should be able to hit a healthy 100 (I give it 60% odds). Everything over 100 is bonus. I’m looking to push past that 122 barrier myself.

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