Mutant males experience a statistically significant lifespan extension when aged at 28 °C, a condition of chronic heat stress (Fig. 3a; P < 0.0001, Fig. S4A).
Indy mutant flies on regular food share many characteristics with CR flies and do not have further longevity extension when aged on a CR diet [ 14, 29, 30].
For example, transgenic mice expressing human mutant APP, generate when aging A β plaques in the hippocampus and cortex, ultimately mimicking the AD-like pathology found in patients.
DNMT3A (3.5±0.9 arbitrary units (a.u).) and DNMT3L (4.1±0.6) were found to be upregulated in the rd1 mutants when compared with age-matched wt (1.0±0.2 and 1.1±0.6 a.u., respectively, P<0.05).
No significant changes in aortic valve and ventricular functions were observed in adult mutant mice when compared with age-matched control (data not shown).
In the opposite case, when animals were aged at 4 °C, female, although not male, mutants exhibited a significant extension of lifespan (Fig. 3b; P < 0.0001 for females, Fig. S4A).
This should be considered when exploring the role of DNA replication stress in driving the acquisition and clonal dominance of mutant HSCs in aging.
However, the double mutant afo1Δ, tor1Δ strain aged more rapidly than the single mutant afo1Δ strain.
However, recombinant CH2 mutants aggregated when they were expressed.
When the mice were aged, the number of gender-dependent genes in wild type mice dropped significantly (127), but not so much in mutant mice (167) suggesting aging narrowed the gender gap more in wild type mice than in the mutant mice (table 8).
