(A) mRNA encoding Nmrk2/Itgb1bp3 was massively increased in Tfr1hrt/hrt mice.
(B) mRNAs encoding Slc3a2 and Slc7a5, components of the uptake system for tryptophan, an NAD precursor, were increased in Tfr1hrt/hrt mice.
(C) mRNAs encoding ADP-ribosyltransferases Art1, Art4 and Art5 were markedly decreased in Tfr1hrt/hrt mice.
(D) Proteins from mitochondria isolated from Tfr1hrt/hrt heart showed increased lysine acetylation.
(E) Administration of NR, an NAD precursor and Nmrk2 substrate, extended the lifespan of Tfr1hrt/hrt mice for up to 5 days.
(F) Levels of UPRMT mRNAs in hearts from WT and Tfr1hrt/hrt mice that were untreated (control group, on left) or treated with NR (right). NR treatment appears to have blunted the UPRMT response.
(G) p62 protein levels in hearts from WT and Tfr1hrt/hrt mice that were untreated or treated with NR.
Data are presented as means ± SEM. P-values for (A) to (C) and (F) were determined by one-way ANOVA. Sample size (n) is indicated; P-value for (E) was determined by Logrank test as described in Supplemental Data; P-value for (G) was determined by two-way ANOVA followed by Bonferroni correction; *p < 0.05; **p<0.01; ***p<0.001.