Undulating changes in human plasma proteome profiles across the lifespan

Aging is a predominant risk factor for numerous chronic diseases that limit healthspan(1). Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues(2–10), which supports a hypothesis that age-related molecular changes in blood could provide novel insights into age-related disease biology. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18–95 years old) and developed a novel bioinformatics approach, which uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh, and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways, which might offer potential targets for age-related diseases.