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longevity/​aspirin directory

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“A Collective Analysis of Lifespan-extending Compounds in Diverse Model Organisms, and of Species Whose Lifespan Can Be Extended the Most by the Application of Compounds”, Berkel & Cacan 2021

2021-berkel.pdf: “A collective analysis of lifespan-extending compounds in diverse model organisms, and of species whose lifespan can be extended the most by the application of compounds”⁠, Caglar Berkel, Ercan Cacan (2021-10-21; ; similar):

Research on aging and lifespan-extending compounds has been carried out using diverse model organisms, including yeast, worms, flies and mice. Many studies reported the identification of novel lifespan-extending compounds in different species, some of which may have the potential to translate to the clinic. However, studies collectively and comparatively analyzing all the data available in these studies are highly limited.

Here, by using data from the DrugAge database, we first identified top compounds in terms of their effects on percent change in average lifespan of diverse organisms, collectively (n = 1,728).

We found that, when data from all organisms studied were combined for each compound, aspirin resulted in the highest percent increase in average lifespan (52.01%), followed by minocycline (27.30%), N-acetyl cysteine (17.93%), nordihydroguaiaretic acid (17.65%) and rapamycin (15.66%), in average. We showed that minocycline led to the highest percent increase in average lifespan among other compounds, in both Drosophila melanogaster (28.09%) and Caenorhabditis elegans (26.67%), followed by curcumin (11.29%) and gluconic acid (5.51%) for D. melanogaster and by metformin (26.56%), resveratrol (15.82%) and quercetin (9.58%) for C. elegans.

Moreover, we found that top 5 species whose lifespan can be extended the most by compounds with lifespan-extending properties are Philodina acuticornis⁠, Acheta domesticus⁠, Aeolosoma viride⁠, Mytilina brevispina and Saccharomyces cerevisiae (211.80%, 76%, 70.26%, 55.18% and 45.71% in average, respectively).

This study provides novel insights on lifespan extension in model organisms, and highlights the importance of databases with high quality content curated by researchers from multiple resources, in aging research.

Figure 1: Top compounds in terms of their effects on average lifespan change in diverse organisms collectively. Percent change in average lifespan of organisms treated with longevity-extending compounds, when data from all organisms studied were combined for each compound. Top plot: Compounds were ordered as the compound which caused the highest percent increase in average lifespan in all organisms combined, given at the top of the plot. Data points for each species were given a different color. Yellow vertical line indicates no change (0%) in average lifespan. Vertical lines in boxplots indicates the median value. Legend shows the color code for each species. Bottom plot: Distribution of the percent change in average lifespan for each drug, when data from all organisms studied were combined per compound. Yellow vertical line indicates no change (0%) in average lifespan. Values in red at the end of x-axis for every y-value indicate mean percent change in average lifespan for each compound. Compounds were ordered as the compound which caused the highest percent increase in average lifespan (aspirin, 52.01%) in all organisms combined, given at the top of plot. Legend shows the color scale indicating percent change in average lifespan.

“Effect of Aspirin on Disability-free Survival in the Healthy Elderly”, McNeil et al 2018

“Effect of Aspirin on Disability-free Survival in the Healthy Elderly”⁠, John J. McNeil, Robyn L. Woods, Mark R. Nelson, Christopher M. Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey et al (2018-10-18; ; similar):

Background: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

Methods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.

Results: A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; p = 0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; p < 0.001).

Conclusions: Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583)

“Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE): a Randomised, Double-blind, Placebo-controlled Trial”, Gaziano et al 2018

2018-gaziano.pdf: “Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial”⁠, J. Michael Gaziano, Carlos Brotons, Rosa Coppolecchia DO, Claudio Cricelli, Harald Darius, Philip B. Gorelick et al (2018-01-01)

“Effect of Daily Aspirin on Long-term Risk of Death due to Cancer: Analysis of Individual Patient Data from Randomised Trials”, Rothwell et al 2011

2011-rothwell.pdf: “Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials”⁠, Peter M. Rothwell, F. Gerald R. FowkesE, Jill FF Belch, Hisao Ogawa, Charles P. Warlow, Tom W. Meade (2011-01-01)

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