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Fig 1.

Vespertilionid bats, including big brown bats (Eptesicus fuscus), live 3-10x’s longer than equivalently-sized mammals but lack visible morphological characteristics indicative of age.

Eptesicus may undergo a thinning of pelage hair throughout life as evidenced by a comparison of two-year old (A) and fifteen-year-old (B) adults. Longevity quotients across mammals (D, modified from [1,7]). Longevity quotient (LQ) = Observed/Expected longevity (from NFM regression) *Vespertilionid bar graph in D indicates longevity of Eptesicus (20-year lifespan) and excludes Myotis (over a 40-year lifespan) as it was not available for this study.

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Table 1.

Summary of the workflow utilized to investigate the metabolic profile of feces in young and elderly bats.

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Table 2.

Fecal analyses detected 41 metabolites with known biological effects that significantly differentiated metabolome of elderly bats.

Metabolites demonstrated ≥2-fold changes and p < 0.05. Log2 abundance ratios for all metabolites were acquired in ESI+ mode.

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Fig 2.

Principle component analysis (PCA) of metabolic profile of fecal samples show separate groupings for age groups.

The young age group is demonstrated by open squares (one-year-old animals) and, filled, black squares (two-year-old animals). The elderly age group is demonstrated by open circles (fourteen-year old animals) and filled, black circles (fifteen-year-old animals). Variation was explained on three axes: x-axis (18.82%), y-axis (7.98%), and z-axis (5.69%).

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Fig 3.

Metabolism of L-Tryptophan can occur as a direct conversion to indole (A), modification to skatole (B), and degraded by the kynurenine pathway (C).

IDO is the most critical enzyme regulating local activity of the Kynurenine Pathway. In response to an infection (via IFN-γ), activation in IDO results a local degradation of tryptophan that limits growth of a pathogen (D). Activation of IDO in cases of chronic inflammation/cancer suppresses the effectiveness of immune cells which creates a sanctuary for pathogen survival and proliferation (E). In contrast, inhibition of the IDO response results in the stimulation of immune cells and catalyzes an immune response that may arrest growth and hinder proliferation of pathogens (F). Metabolites with high concentrations in the feces of elderly Eptesicus are indicated by yellow boxes.

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