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A metabolic pattern of atropine in man, based on the detection of radiolabelled products in urine by high performance liquid chromatography after administration of [3H]atropine sulphate to a normal volunteer is proposed. Noratropine (24%), atropine-N-oxide (equatorial isomer) (15%), tropine (2%) and tropic acid (3%) appear to be the major metabolites, while 50% of the administered dose is excreted as apparently unchanged atropine. No conjugates were detectable. Evidence that atropine is present as (+)-hyoscyamine was found, suggesting that stereoselective metabolism of atropine probably occurs.

1 Urine specimens of 8 organophosphate-poisoned patients on treatment with large doses of atropine were screened for atropine metabolites using thin-layer chromatography. Only atropine was detected. 2 High performance liquid chromatography of urine specimens of a poisoned patient receiving large doses of atropine likewise detected only 3H-atropine after administration of 30 μCi 3H-atropine-sulphate. In the urine of a normal human volunteer treated with a single dose of 3H-atropine, 5 metabolic products were detected by this method. 3 It is concluded that acute organophosphate-poisoning blocks atropine metabolism by inhibiting the hepatic microsomal enzymes.

Developing targeted therapies first requires a working definition of the condition of interest. Unfortunately for aging, this very initial step poses a challenge since chronological age is often not indicative of biological age nor modifiable. This symposium will demonstrate the enormous progress being made towards developing more reliable and valid measures for quantifying biological aging. First, Dr. Albert T. Higgins Chen will show how inaccuracy caused by noise at individual CpG sites can lead to high technical variability in the most widely applied biomarkers of aging—epigenetic clocks. He will further discuss how this can be overcome through novel statistical techniques. Second, Dr. Benoit Lehallier, will discuss plasma proteomic clocks and share insights into their potential roles in Alzheimer's disease and utilization in clinical trials. Third, quantifying the multifactorial aging process can be facilitated by projects incorporating multimodal biomarker data. Pei-Lun Kuo from the Baltimore Longitudinal Study of Aging will present an analysis of longitudinal trajectories of more than 30 phenotypes, which when combined into a single summarized score yield important insights. Fourth, our ability to uncover aging mechanisms and perform drug screens, requires valid and reliable measures that can be applied in vitro. Christopher Minteer who developed in cellulo epigenetic markers will demonstarte how epigenetic aging changes that can be induced in culture shed light on aging in vivo. Finally, a summarizing discussion will be held by Dr. Nir Barzilai, an expert in the field, who is leading the Targeting Aging with Metformin (TAME) clinical trial.