Dietary Restriction Induced Longevity is Mediated by Nuclear Receptor NHR-62 in Caenorhabditis elegans

Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the C. elegans HNF4a- related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat- 2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, increased autophagy, and changes in fatty acid composition are partly reversed by mutation of nhr-62. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence that nuclear hormone receptors regulate the DR response, suggesting hormonal and metabolic control of life span.

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

iological optimization of proton therapy critically depends on detailed evaluation of relative biological effectiveness (RBE) variations along the Bragg curve. The clinically accepted RBE value of 1.1 is an oversimplification, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak. We observed significant cell killing RBE variations dependent on beam modulation, intrinsic radiosensitivity, and LET in agreement with the LEM predicted values, indicating dose-averaged LET as a suitable parameter for biological effectiveness. Data have also been used to validate a RBE parameterized model.