SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species.

DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.

A Step Toward Health Equity for Veterans: Evidence Supports Removing Race From Kidney Function Calculations.

BACKGROUND: The practice of race-based medicine fails to recognize that race cannot be used as a proxy for genetic ancestry and that racial and ethnic categories are complex sociopolitical constructs without biological basis. Clinical algorithms and equations that incorporate race modifiers and are currently considered standard for diagnosis and management of disease are appropriately being scrutinized for lack of biological plausibility and their role in exacerbating health inequities. In this paper, we review the history, evidence, and implications of using a Black race coefficient when calculating estimated glomerular filtration rate (eGFR) in the diagnosis and management of kidney disease. OBSERVATIONS: Currently, the US Department of Veterans Affairs (VA) uses the Modification of Diet in Renal Disease (MDRD) equation for eGFR. This equation includes a Black race coefficient that results in an eGFR that is 21% higher for a Black patient when compared with a patient of any other race. The rationale for the inclusion of this coefficient is based on racist science that incorrectly assumes race as a proxy for genetic ancestry. Multiple studies across diverse Black populations demonstrate that the application of a race coefficient in kidney function estimation equations is inferior when compared with the race-neutral option. Furthermore, the most utilized eGFR equations are biased and imprecise. Because eGFR is the primary diagnostic method for detecting and managing kidney disease, preventing its progression, planning for dialysis, and evaluating for transplantation, it is vital that eGFR be as accurate, precise, and equitable as possible. CONCLUSIONS: The incorporation of a race coefficient in kidney estimation equations lacks biological plausibility and its use exacerbates kidney health disparities. Until a better method to estimate kidney function becomes available, a race-neutral option for current estimation equations should be applied for all patients.

Opioid drug poisonings in Ohio adolescents and young adults, 2002-2014.

CONTEXT: Opioids represent a drug class that adolescents and young adults intentionally misuse and abuse. When taken on their own or with other substances in this manner, opioids pose an increased risk of overdose and potential death. OBJECTIVE: To determine trends of opioid drug poisonings among adolescents and young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data. METHODS: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug poisonings amongst 10-29 year olds. Trends were evaluated with Poisson regression. Ohio counties with higher opioid drug poisoning rates were identified using age-adjusted resident population estimates. Chi-square tests were conducted to compare these county rates to the Ohio rate. RESULTS: Both unintentional and intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were significant declines through 2014. Almost 40% of intentional opioid drug poisonings were for young adults aged 18-24 years. Suspected suicide poisonings were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were 60.1% male. Commonly reported substances included tramadol, heroin, and acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and ethanol were the most common substances reported in conjunction with opioids. The top four Ohio counties with significantly higher opioid drug poisoning rates than the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield. CONCLUSION: This study enhances the understanding of Ohio's opioid epidemic so that future prevention efforts and legislation can better target needed resources. Both males and females would benefit from opioid education early in their lives.