Translational approaches to targeting the biological

Translational approaches to targeting the biological basis of aging is a rapidly-developing field. discuss targeting cellular senescence programs to improve fitness. Among these approaches are so-called senolytic agents, which selectively clear senescent pitavastatin and relieve the associated pathophysiology they confer. Another approach is caloric restriction. Recapitulated from yeast to invertebrate animals to rodents to primates including humans, stringently regulating food intake has shown beneficial effects on longevity and health. discuss some of the underlying mechanisms of caloric restriction and how they may be harnessed to intervene in age-related phenotypes. elaborate on dietary interventions as part of the US National Institute on Aging\'s Interventions Testing Program to identify modifiers of lifespan in pre-clinical models before translation to human trials. Accurately defining one\'s age may assist with the timing of appropriate interventions. Instead of using chronological age and epidemiological data to assess a patient\'s risk of age-related function or illness, discuss predictors of biological age, utilizing molecular markers to reliably predict one\'s personalized risks. Finally, discuss frailty, with particular attention to an individual\'s postural control as not only a readout of overall fitness but also as a key target for improving quality of life. This special section on Aging and Metabolism highlights both the considerable impending need healthcare systems must meet in managing an aging population, but also the remarkable progress researchers have made and continue to make to meet these needs. We wish to thank the authors of the In Focus and Review articles presented in this issue of for emphasizing the diverse issues being tackled by the geroscience community, as well as consultants Thomas von Zglinicki and Rozalyn Anderson who helped shape this special issue section, and the referees who provided valuable feedback to strengthen each manuscript. Given the enthusiastic commitment among the geroscience community to—as the UN SDG states—ensure healthy lives and promote well-being for all at all ages, looks forward to the continued rapid development of this burgeoning field.
The Interventions Testing Program (ITP) was established by the National Institute on Aging (NIA) to investigate the potential of dietary interventions to promote healthy aging (). The ITP uses a four-way cross genetically heterogeneous mouse model (UM-HET3) to reduce the impact of strain-specific characteristics on outcomes (). Lifespan tests are done in parallel, using the same protocol, at three independent sites to increase robustness of the findings. Population sizes are large enough that the protocol will detect a 10% change in mean lifespan, in either sex, with 80% power, pooling data from as few as two sites. Standard operating procedures were designed to maintain as much consistency as possible among the three sites, including caging, bedding, food, and light/dark cycles; a more in-depth discussion of the SOP has been published (). Interventions for testing are proposed by the research community through an annual call-for-proposals, and proposed compounds have ranged from drugs and dietary supplements to micronutrients and metabolic intermediates. Before the ITP embarks on testing a compound, pilot studies are done to maximize the chances of a successful test. Goals of the pilot studies include demonstrating that the compound is stable in food and that it is uniformly mixed in the food, determining blood levels after short-term treatment (bioavailability), showing evidence of an effect from the short-term treatment (bioactivity), and in some cases, testing for toxicity. The testing of rapamycin is a good case-in-point for analyzing stability of the compound in the food. Pilot analysis showed that about 85% of the rapamycin was degraded by the food preparation process, leading to the use of microencapsulation to deliver stable doses of the compound in food ().