Monday, April 19, 2010

Aging, the E. coli Way

Reading Carl Zimmer’s Microcosm: E. coli and the New Science of Life, I came across a reference about aging in E. coli – a 2005 PLoS Biology paper “Aging and Death in an Organism That Reproduces by Morphologically Symmetric Division.” Four researchers from France described their measurements of individual E. coli cells growing old.

I know all this sounds like a fairy-tale. After all, we tend to see the life of bacteria as immortal. Making up a kingdom of life that populates every corner of the earth, they seem either to keep dividing actively or to wait for such chances in their dormant forms. Once upon a time, our awe for their vigor was even expressed in our hypothesis that they enjoyed a fictitious everyday spontaneous origin. The news, that bacteria generate wrinkles and diseases for themselves, dropping into the 21st century ears, perhaps sounds even stranger than that that fiction in the 19th century.

Having played with E. coli for five years, I have indeed seen their deteriorations for a few times. Once E. coli liquid cultures are set up, the inoculated cells, often invisible initially, would start to glut the rich nutrients, and multiply into dense crowds overnight, which give the cultures cloudy appearances. Left in the incubator for more than two days by, for example, inadvertent researchers, however, they would deplete nutrients and shrink into dilapidated films. This is no surprise since all life forms require some source of energy. But this is also not what the authors mean by aging E. coli. They do not mean degeneration or death caused by famine or other harsh environments. They were serious in a deteriorating process that was dependent solely on the growth history of cells in a wholesome environment.

Growth for E. coli means cell division. Rod shaped, they would produce progeny through elongation, and sever from the middle of the cell bodies into two rods. In each division, Eric Stewart et al. define the end of the E. coli progenies that utilized their mother’s end as the old pole; the end generated anew as the new pole (see the figure below). The authors monitored the process of cell divisions from one cell to up to 500 cells (see the video), and ask the question: do the cells incorporating older poles behave differently from cells with newer poles?

The authors measured specifically of how fast the newly generated cells from divisions started the next round of proliferation. They observed that, indeed, within the same generations, the cells with older poles took longer to start dividing for the next time. Across generations, the difference in reproductive rates also widened: the more generations the old pole went through in a cell, the longer it took to initiate the next round of division. In the end, 16 among about 500 cells could not even start dividing any more, therefore were defined “potentially dead cells.” The authors deemed such phenomenon reflecting an aging process that involves declined rates of reproduction and increased death rates in bacteria.

There had been much publication before 2005 showing that some fungi or bacteria can divide asymmetrically, thus dumping most of their old biochemical trash to one of their progenies, making them senescent, while keeping the other offspring rejuvenated. The significance of the research by Stewart et al. lies in that they showed even morphologically symmetrical divisions can produce aging of there progenies, because a chemical or structural symmetry can never be absolutely achieved in cell divisions. The authors further hypothesized that this bacterial way of aging may provide a relic that still contribute to the aging of more advanced organisms.

With neat design of experiments and interesting discussions, however, this research triggered my qualms. In most basic consideration, I doubt whether the correlation between “old poles” and declined rates of proliferation indicate a biologically real state of aging. It might have been a growth signaling mechanism, like quorum sensing (bacteria release chemical to reduce the reproductive rates when the population reach higher density), to which old poles hypothetically have more reactivity.

Another doubt concerns with the fate of the species of E. coli. According to the authors, the reproductive efficiency would keep diminishing as E. coli cells proliferate. As the old pole becomes ever older with each division, the cells would eventually stop dividing at all. Unlike multicellular organisms, which enjoy the magic of rejuvenation in their germ cells, E. coli without a generational rejuvenation seems to be doomed. Indeed, while more advanced organisms age as individuals, the symmetrical aging of microbes is synonymous to the aging of their species. If E. coli has its own elixirs, or a hypothetical one, it should not have escaped from the scope of the authors’s discussion.

The third group of considerations is more philosophical: to what extent can we really define the loss of reproductive power as a sign of aging, especially for individual cells? If the “age” situation in dividing cells are determined more by the structural and chemical conditions of a cell, not by the passing of time, why should we call such conditions “aging” processes? If such aging of microbes contribute somehow to our aging evolutionally, can we also say it in a reverse way, that this misnomer of aging in E. coli is only a relic from our lasting consideration of the aging in our species?

Yes, no one is immortal. But is saying that equal to say that every living thing is aging?

Stewart EJ, Madden R, Paul G, Taddei F (2005) Aging and Death in an Organism That Reproduces by Morphologically Symmetric Division. PLoS Biol 3(2): e45. doi:10.1371/journal.pbio.0030045

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