Conserved and species specific molecular denominators in mammalian aging [mouse]

Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.

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Mercken EM, Capri M, Carboneau BA, Conte M, Heidler J, Santoro A, Martin-Montalvo A, Gonzalez-Freire M, Khraiwesh H, González-Reyes JA, Moaddel R, Zhang Y, Becker KG, Villalba JM, Mattison JA, Wittig I, Franceschi C, de Cabo R