The unicellular origin of biological senescence: Its evolution and population dynamics

University Of California-San Diego, La Jolla CA

Investigators

Abstract

The supported research project investigates the origin of biological aging in single-celled organisms such as bacteria. The hypothesis to be tested is that whenever bacteria accrue non-genetic damage, such as oxidized proteins, it is more advantageous for a mother cell to reproduce by allocating asymmetrically more damage to one of her two daughter cells. Because damage causes a cell to grow more slowly, the daughter receiving less damage is rejuvenated and the one receiving more is aged. The advantage of asymmetry was predicted by a theoretical analysis conducted with a computational model and it can be illustrated with an investment analogy. Consider having bank accounts A ($1,000 at 8% yearly) and B ($500 at 6% and $500 at 10%). If more money is the goal, account B has more after two years. Partitioning damage asymmetrically generates a fast and a slow growing daughter, and it is equivalent to having account B. Partitioning damage symmetrically is comparable to account A. The demonstration that bacteria age would overturn a long standing dogma in biology that aging is a characteristic of only complex and multi-cellular organisms such as humans. If bacterial aging is real, a scientific paradigm will have shifted and text books will have to be rewritten. Moreover, if aging is universal to both bacteria and humans, a common mechanism may exist and the results of this study would help guide research on aging in all organisms. If there is a common mechanism, a common solution may also exist. The fact that human aging is often also associated with oxidative damage is already a promising link. A unicellular origin of aging does not require natural selection on groups because it is the fitness of the lineage that is maximized by the asymmetrical partitioning of damage. Two sets of experiments with the bacterium Escherichia coli will be completed to test the proposed models of aging in the supported research. First, the effect of short term variation in the level of damage experienced by a single bacterial species will be examined. Second, the degree of asymmetry will be estimated and compared for different bacterial species that have evolved over long term under high levels of damage. Damage levels will be manipulated by adding extrinsic damage agents (e.g. heat, peroxides, antibiotics, and radiation). The analyses of the theoretical models predict (i) that short term variation in damage levels causes the bacteria to transition from immortality to mortality and (ii) that long term exposure to high levels leads to the evolution of higher degrees of asymmetry. The degree of asymmetry is quantified by the asymmetry parameter in the models. The parameter is estimated by fitting the models to population data, which are the doubling or generation time of individual cells estimated by time-lapse microscopy of dividing bacterial populations. Novel insights will be attained by this robust investigation of bacterial aging providing the framework to readdress both the short-term and long-term aspects of the population dynamics and evolution, respectively.