New Paper: Lifespan Benefits for the Combination of Rapamycin plus Acarbose in mice

Another example where starting longevity drugs earlier in life result in better outcomes over starting later in life. In this study, the mice that started at age 9 months (equivalent to approx. 30 years old in human terms), lived 28% to 34% longer, whereas mice that started at age 16 months (equivalent to approx. 50 to 60 years in human terms) only lived 13% longer:

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding.

Here, we extend this strategy, testing rapamycin and acarbose in combination, starting at 9 or 16 months of age, based on a similar rationale to that used for the metformin/rapamycin trial.

Rapamycin plus acarbose, starting at 9 months of age (RaAc9) . This combination of agents produced a 28% increase in median lifespan in females (p < 0.0001) and a 34% increase in males (p < 0.0001) for data pooled across sites (Figure 1). This was the only treatment that significantly increased survival in both sexes at all three sites tested separately.

Rapamycin plus acarbose, starting at 16 months of age (RaAc16) , increased median lifespan by 13% both in females (p < 0.0001) and in males (p < 0.0001), using data pooled across sites (Figure 1). Site-specific analyses, shown in Tables 2 and 3, revealed a significant extension of lifespan at all sites for females, but only at UT for males. In females, RaAc16 extended median lifespan by 21% at TJL (p < 0.0001), 5% at UM (p = 0.01) and 18% at UT (p < 0.0001). RaAc16 increased 90th percentile survival for pooled data in both sexes (p < 0.001; Table 1) and at each site individually for females. In males, RaAc16 extended median lifespan of UT males by 32% (p < 0.0001). The RaAc16 effect on male survival was significant only at UT.

Captopril, started at 5 months , increased the median lifespan in females by 6% (p = 0.002) and in males by 13%

More reading:

Acarbose: Acarbose - Details On Another Top Anti-Aging Drug

Full Paper:

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice


How should we take Acarbose? I don’t know anything about this drug. Should it be a dose before a carby meal? A dose early in the morning? Late at night? What dosage should be taken? Thanks for the help as I am considering adding this drug.


I’ll be making an Acarbose guide hopefully within the next few days. Including its metabolic benefits, Dosing, Methods to enhance the efficacy, And its limitations in blunting glucose spikes and potential pitfalls.


Great, Rami! Share it here on :pray: Are you taking acarbose and/or rapamycin? If yes, what dose regime are you using?

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Yes - its dosed every meal, with the first bite of the meal. It lasts/is effective for about 2 hours after you take it. Dosing is 25mg to 50mg to 100mg tablets. Read this thread: Acarbose - Details On Another Top Anti-Aging Drug


Curious, is there a cohort that combines rapa + metformin + acarbose? To see if metformin and acarbose have synergistic effects?


Not yet. The ITP has only done combinations of two drugs so far.

Here is a list of all the compounds tested (and being tested right now) by the ITP, and combinations of compounds/drugs:

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Is it just me, or does the ITP testing only 6 compounds a year seem very small? I think we need more trials.

Just out of curiosity, does anyone know how much it costs to fund a mouse trial at the ITP? Do they accept donations to do more?


Yes - its insane. The annual budget for the ITP program is about $5 Million I believe. I think each mouse trial is about $500K. Rediculously underfunded given the NIH budget is $45 Billion.

The Interventions Testing Program (ITP) tests intervention strategies that may delay aging in mammals under standardized conditions.The interventions’ effects on aging are measured by lifespan extension and/or delayed onset/severity of late life pathologies. Compounds are proposed by the research community and the general public. Pilot studies of compound stability, toxicity, and bioavailability are performed before new compounds are entered into the testing pipeline. Testing by the ITP follows two Stages: Stage I and Stage II. In Stage I studies, a single dose of a candidate compound is administered chronically from an established adult age. In Stage II studies, multiple doses, different administration regimens, multiple compounds, or a combination thereof are tested based on promising data from Stage I studies. Lifespan is the primary outcome for the ITP. Secondary outcomes include, but are not limited to, geropathology assessment at set time-point(s) after initiating the intervention and pathology at death, selected animal vital records (e.g., weight) across the lifespan, and molecular phenotypes. The ITP also collects tissues that are made available to the research community for ancillary studies through the Interventions Biospecimens Repository (IBR). A Data Coordinating Center (DCC) supports the ITP by providing a hub for storing documentation and data, performing statistical analyses, and ensuring the public sharing of the data generated by the ITP through a dedicate

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$5 million is just lip service, but better than nothing. Seriously, they should consider ponying up about 10X more. That’d still only be 0.1% of their budget!

I wonder how much other diseases get for funding?

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The national cancer institute gets $7.3 Billion/year:

Here are all the other categories under the NIH:

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Aging actually has a large budget:

Aging $2,556 $2,698 $3,150 $3,572 $4,084 $4,653 $5,276 $5,657 $6,069 $5,838

Lot’s of small grants in the $100,000s. I guess it’s the shotgun effect to promote small research projects. So, in comparison, $5,000,000 is a pretty big project.

Lots of amyloid-Alzheimers studies. I thought they said the amyloid/Alzheimer link was based on bad data. They sure are throwing billions of dollars at it though!

Mostly its alzheimers related… Not aging. The biology of aging dept only gets about $350 million a year.

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Seems they think Alzheimer’s is synonymous with aging.

Right… Pretty stupid. Why is alzheimers classified as “aging” but cancer not? Seems pretty arbitrary.

Cancer trend with Age:

Age-specific incidence of Alzheimer’s disease (per 1000 person years) across continents and countries. *, incidence of all types of dementia


That’s really sad, why can’t ITP program get more fund? Are there any way that we can help ITP program?