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SummaryThe metabolism of tryptophan to nicotinamide adenine dinucleotide (NAD+) through the kynurenine pathway is increasingly linked to aging and age-associated disease. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses, cellular redox homeostasis, and energy production. Aberrant kynurenine metabolism is observed during normal aging and has been implicated in a range of age-associated pathologies, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. In previous work, we and others identified three genes—kynu-1, tdo-2, and acsd-1—encoding kynurenine pathway enzymes for which decreasing expression extends lifespan in invertebrate models. Here we report that knockdown of haao-1, a fourth kynurenine pathway gene encoding the enzyme 3-hydroxyanthranilic acid dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated decline in health in Caenorhabditis elegans. This lifespan extension is mediated by increased physiological levels of the HAAO substrate 3-hydroxyanthranilic acid (3HAA). 3HAA increases resistance to oxidative stress during aging by directly degrading hydrogen peroxide and activating the Nrf2/SKN-1 oxidative stress response. Aging mice fed a diet supplemented with 3HAA are similarly long-lived. Our results identify HAAO and 3HAA as novel therapeutic targets for age-associated disease. This works provides a foundation for more detailed examination of the molecular mechanisms underlying the benefits of 3HAA, and how these mechanisms interact with other interventions both within and beyond the kynurenine pathway. We anticipate that these findings will bolster growing interest in developing pharmacological strategies to target tryptophan metabolism to improve health aging.

The aim of this study was to analyze the incidence and associated charges of fecal impaction for trends in hospital and patient demographics in emergency departments (ED) across the United States.In 2010, an ICD-9-CM code (560.32) for fecal impaction was introduced, allowing for assessment of fecal impaction incidence.Data were obtained from the National Emergency Department Sample records in which fecal impaction (ICD-9-CM code 560.32) was first listed as a diagnosis in 2011.In 2011, there were 42,481 [95% confidence interval (CI), 39,908-45,054] fecal impaction ED visits, with an overall rate of 32 fecal impaction visits per 100,000 ED visits. Adjusted for inflation in 2014 dollars, the associated mean charge of a fecal impaction ED visit was $3060.47 (95% CI, $2943.02-$3177.92), with an aggregate national charge in the US of $130,010,772 (95% CI, $120,688,659-$139,332,885). All charges were adjusted for inflation and reported in 2014 dollars. Late elders (85+ y) had the highest rate of fecal impaction ED visits, followed by early elders (65 to 84 y). Medicare was the primary payer for the greatest number of fecal impaction ED visits accounting for nearly two thirds of visit payments.This study reports previously unexplored statistics on the number, frequency, and associated charges of ED visits with a primary diagnosis of fecal impaction, a condition found most commonly among elders.

Although constipation is typically managed in an outpatient setting, there is an increasing trend in the frequency of constipation-related hospital visits. The aim of this study was to analyze trends related to chronic constipation (CC) in the United States with respect to emergency department (ED) visits, patient and hospital characteristics, and associated costs.Data from 2006 to 2011, in which constipation (The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes 564.00-564.09) was the primary discharge diagnosis, were obtained from the National Emergency Department Sample (NEDS).Between 2006 and 2011, the frequency of constipation-related ED visits increased by 41.5%, from 497,034 visits to 703,391 visits, whereas the mean cost per patient rose by 56.4%, from $1,474 in 2006 to $2,306 in 2011. The aggregate national cost of constipation-related ED visits increased by 121.4%, from $732,886,977 in 2006 to $1,622,624,341 in 2011. All cost data were adjusted for inflation and reported in 2014 dollars. Infants (1 year old) had the highest rate of constipation-related ED visits in both 2006 and 2011. The late elders (85+ years) had the second highest constipation-related ED visit rate in 2006; however, the 1- to 17-year-old age group experienced a 50.7% increase in constipation-related ED visit rate from 2006 to 2011 and had the second highest constipation-related ED visit rate in 2011.The frequency of and the associated costs of ED visits for constipation are significant and have increased notably from 2006 to 2011.