Personal aging markers and ageotypes revealed by deep longitudinal profiling

Abstract

The molecular changes that occur with aging are not well understood [1][2][3][4] . Here, we performed longitudinal and deep multiomics profiling of 106 healthy individuals from 29 to 75 years of age and examined how different types of 'omic' measurements, including transcripts, proteins, metabolites, cytokines, microbes and clinical laboratory values, correlate with age. We identified both known and new markers that associated with age, as well as distinct molecular patterns of aging in insulin-resistant as compared to insulin-sensitive individuals. In a longitudinal setting, we identified personal aging markers whose levels changed over a short time frame of 2-3 years. Further, we defined different types of aging patterns in different individuals, termed 'ageotypes', on the basis of the types of molecular pathways that changed over time in a given individual. Ageotypes may provide a molecular assessment of personal aging, reflective of personal lifestyle and medical history, that may ultimately be useful in monitoring and intervening in the aging process.Aging is a universal process of physiological and molecular changes that are strongly associated with susceptibility to disease and ultimately death [1][2][3][4][5] . Despite its importance and extensive analysis in model organisms, a comprehensive view of the molecular changes that occur during aging in humans is not known and understanding of the heterogeneity of the aging process at an individual level and over short actionable timescales is lacking.Cross-sectional studies have revealed differences in telomeres and DNA methylation associated with age 6 . The latter has led to a description of a 'molecular clock' that is associated with chronological and biological age 7,8 . Acceleration of the clock has been associated with human diseases. In addition to epigenetic markers, several clinical markers, *

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