PT  - JOURNAL ARTICLE
AU  - Timothy V. Pyrkov
AU  - Konstantin Avchaciov
AU  - Andrei E. Tarkhov
AU  - Leonid I. Menshikov
AU  - Andrei V. Gudkov
AU  - Peter O. Fedichev
TI  - Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts ultimate limit of human lifespan
AID  - 10.1101/618876
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 618876
4099  - http://biorxiv.org/content/early/2019/04/26/618876.short
4100  - http://biorxiv.org/content/early/2019/04/26/618876.full
AB  - We analyzed aging trajectories of complete blood counts (CBC) and their association with the incidence of chronic diseases and death in cohorts of aging individuals registered in the UK Biobank and National Health and Nutrition Examination Survey (NHANES) studies. Application of a pro-portional hazards model to the CBC data allowed us to identify the log-transformed hazard ratio as a natural biomarker of aging, which we have named the dynamic morbidity index (DMI). DMI increased with age in the UK Biobank and NHANES cohorts, was associated with frailty, and pre-dicted the prospective incidence of age-related diseases and death. To better understand the nature of DMI variations along individual aging trajectories, we acquired a sufficiently large longitudinal database of CBC measurements from a consumer diagnostics laboratory. We observed population DMI distribution broadening associated with a progressive loss of physiological resilience measured by the DMI inverse auto-correlation time. Extrapolation of this data suggested that DMI recovery time and variance would simultaneously diverge at a critical point of 120 – 150 years of age corresponding to a complete loss of resilience. We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors and signifies a fundamental or absolute limit of human lifespan.