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. Author manuscript; available in PMC: 2012 Feb 1.
Published in final edited form as: Prog Neurobiol. 2010 Dec 2;93(2):165–181. doi: 10.1016/j.pneurobio.2010.11.006

Fig. 13. Model of age by disease interaction.

Fig. 13

Adapted from (Glorioso et al., 2010). As loss of expression of disease-related genes below homeostatic threshold (horizontal red line) marks the onset of symptoms, we hypothesize that changes in the trajectory of age-related changes of disease-related genes (Y-axis) determine at what age (X-axis), or if, an individual may develop symptoms (vertical red arrows), manifested as functional declines. Modulators (blue arrows) may thus place individuals on “at risk” or “protected” trajectories. For instance, SIRT5 C/C-allele carriers are on an accelerated trajectory (i.e., older molecular ages) compared to C/T-allele carriers particularly for mitochondrial PD-related genes (Fig. 11, 12). The net result is that risk-allele carriers may cross threshold for disease onset and/or functional declines at earlier ages. Alternate trajectories not shown include lower expression levels of disease-related genes at all ages, or upward trajectories for genes with gain of function in disease and aging (i.e., upregulated Clusterin in aging and AD (Calero et al., 2000; Erraji-Benchekroun et al., 2005)).