There is initial evidence, mostly derived from model organisms, that the phenotypic manifestation of aging are determined by a specific biological process that is also implicated in the pathophysiology of most age-associated chronic diseases and disabilities. We have made considerable progress in understanding and assessing the phenotypical manifestation of aging, and to certain extent to differentiate aging from diseases in humans. However, the search for the core mechanism of biological aging in humans has just started. We plan to enroll a cohort of 100 individuals dispersed over a wide age-range and extremely healthy based on strict, highly standardized criteria (IDEAL criteria). These participants will be deeply phenotypically characterized using the same protocol that is utilized in the Baltimore Longitudinal Study of Aging. In addition, we will obtain large amount of PBMCs through cytapheresis and sorte them in 10 cell types, representing >99% of PBMCs. We will also obtain muscle and skin specimens through biopsies. We plan to use these samples to perform a number of omics, including RNAseq, methylome, proteome and metabolome to understand to verify the hypothesis that molecular signatures exists that track aging across cell types and are associated with the main aging phenotypes (body composition, energetics, homeostatic equilibrium, neurological function. In this discovery study we look for molecular clue that may reveal the intrinsic mechanisms of aging that can be targeted for interventions.
|Gonzalez-Freire, Marta; Semba, Richard D; Ubaida-Mohien, Ceereena et al. (2017) The Human Skeletal Muscle Proteome Project: a reappraisal of the current literature. J Cachexia Sarcopenia Muscle 8:5-18|
|Levine, Morgan E; Lu, Ake T; Chen, Brian H et al. (2016) Menopause accelerates biological aging. Proc Natl Acad Sci U S A 113:9327-32|