Autoimmunity, calorie restriction, and core body temperature

PROJECT SUMMARY
Calorie restriction (CR) is a balanced reduction of caloric intake that promotes healthy aging and longevity
without causing malnutrition. Importantly, in earlier studies, CR was also found to reduce autoimmunity in
several mouse models of lupus. A striking effect of CR in mice is the reduction of the core body temperature
(Tb) during sleep, which is lowered by up to 10°C compared to mice fed ad libitum (AL). Here, we hypothesize
that this amplified Tb reduction is crucial for the beneficial effects of CR. Consistent with this hypothesis, our
preliminary results suggested that the CR-associated inhibition of lupus-like autoimmunity, especially kidney
disease, is lost if mice are housed under conditions of thermoneutrality (TN, achieved at the ambient
temperature of ~30°C), which does not allow body heat dissipation and hence prevents Tb reductions in CR
mice. Thus, studies are proposed to investigate the effects of CR and TN on circadian Tb profiles in lupus
mice at different disease stages, assess the long-term impact of CR and TN on lupus disease, and determine
the effects of CR and TN on gene expression signatures in lupus kidneys and spleen using single cell and
spatial transcriptomics. The proposed studies are highly significant, particularly for translational applications
of CR in humans, since humans use behavioral thermoregulation (clothes, duvets, air conditioning) to live at
TN.

Grant Number: 1R21AI194047-01
NIH Institute/Center: NIH
Principal Investigator: ROBERTO BACCALA