Fig. 2. The ground zero model or organismal life and aging.

(A) Molecular features associated with aging are U-shaped. During early embryogenesis, telomeres are extended, and entropy is decreased, suggesting a transition from an older to a younger state, but after the inflection point, defined as the ground zero state (or period), their trajectories are reversed. The actual changes of features associated with aging during development may be more complex, e.g. be asynchronized or in waves. (B) Ground state as the beginning of organismal life and aging. The biological age of an organism decreases in early embryogenesis and increases starting at mid-embryogenesis. The ground zero corresponds to the lowest biological age of an organism. In this model, the zygote defines the beginning of cellular life, and the ground zero represents the beginning of organismal life. (C) The beginning of aging at mid-embryogenesis suggests approaches to achieve a lower biological age than that naturally possible. In the ground zero model, the period from the zygote to the ground zero represents rejuvenation, and aging begins at the ground zero. Extending or enhancing the rejuvenation period (as well as reducing the load of damaging mutations) may lead to a lower biological age (green) than naturally achieved (purple) at the ground zero, and therefore a reduced biological age throughout life, leading to an extended lifespan and healthspan.