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Background: Research conferences generally cluster scientists by discipline and limit cross-disciplinary communication. Rushed presentations frequently truncate messages. Travel costs prevent most scientists from ever meeting one another. And delays prior to publication and [sometimes] year-long web-posting embargoes impede the progress we all desire. In some research areas preclinical and clinical trials have replication problems so severe that the US-National Institutes of Health funded a replication program which then failed to replicate 15 of 16 key studies [see PMIDs: 18838063,22078760,22134153,22177997]. Because the plenary discussion of the first large-scale healthspan/longevity trial, the TAME trial (Targeting/Taming Aging with MEtformin), was cut short by time constraints, a communication group formed to continue the healthspan-trial-design discussion after the American Aging Association conference (AAA-2016), thereby improving/speeding communication between conferees and with IAGG-2017 and other healthspan-related conferences.

We review studies on the pharmacology and mode of action of pyrantel and comment on its analogs, oxantel and morantel, where appropriate. Pyrantel is a fairly selective agonist of nematode nicotinic acetylcholine receptors (nAChRs). Pyrantel produces depolarization and contraction of nematode body muscle which causes spastic paralysis; it is a relatively potent agonist (EC50~10 µM) on levamisole receptor subtypes of nematode nAChRs. In addition, pyrantel has open-channel blocking effects which reduce the response at higher agonist concentrations, weak anticholinesterase effects, and nicotinic agonist effects at higher concentrations in vertebrate tissues; pyrantel causes spastic paralysis in chicks, contracts the frog rectus abdominis muscle, depolarizes the end-plate potential in the rat hemi-diaphragm, and causes depolarization and then neuromuscular block in the cat soleus and tibialis muscle preparations. Pyrantel selectively activates a subgroup of nematode nAChRs and at toxic doses has effects on host nAChRs.

The amino acids cysteine, glycine, serine and tyrosine all increased steadily during evolution of primate to human milk, hinting that this combination may support the extraordinary human longevity which co-evolved. Methionine continued its long downward trend during primate evolution, so this amino acid declined steadily in heart tissue and then milk proteins from mice to man, spanning cat, dog, cow, horse and elephant evolution as well as rodent and primate. These amino acid changes are sufficiently precise to enable unbiased SIMCA multivariate analysis to predict primate/human lifespan with 99 percent accuracy, and to score and map all foods within the US Department of Agriculture Nutrition Database (Release 26) into zones comprised of proportions resembling short-lived species, or milk from the longest-lived primates. This presentation provides a tour of foods with longevity-correlated proportions, generally higher in serine and tyrosine and lower in methionine, which map together in 20-dimensional amino-acid-space near human milk, caviar and germ-line tissues that defy aging indefinitely. These carefully-evolved proportions are then linked to daily circadian peak periods of high methionine and genetic damage that by hypothesis represent a burst of daily aging that occurs unless we protect ourselves by carefully selecting nutrient proportions at each meal (either baboon-like proportions or non-aging-germ-line proportions). Longevity-linked ratios in burritos are then shown to predict surprisingly low rates of Alzheimer’s, cancer, heart disease, stroke and other age-associated illnesses within Hispanic-Americans aged 80 and above, and the partial reversal of advanced kidney disease when cats are fed a specially-formulated kidney-support diet.