Infection of Ad-Flag-HMGB1K282930R and Ad-Myc-SIRT1 conferred significant protection against lethality and improved survival during endotoxemia (survival rate, 85.7%) compared to infection of Ad-Flag-HMGB1K282930R alone (survival rate, 15.3%). Here, SIRT1 is linked to serum lipopolysaccharide activity.