Aging in Esherichia coli:signals in the noise

Sir,

The article by Conrad Woldringh in the last issue(1) con-

cerning aging in Escherichia coli raises an important point,

namely that the apparently large variability in the physical

parameters of growing bacterial cellsmakes it difficult to detect

small, systematic differences. We find that old pole cells

(whichwedefined as the parent cells) growabout 2%slower,(2)

on average, than new pole cells (offspring cells), within a

population of cells where the coefficient of variation of the

observed growth rate is approximately 12%. Woldringh points

out in figure 2 of his review that, given previously reported

coefficients of variation in time to divide and length at division

(20% and 10% respectively(3)), growth rate differences of a

few per cent can result in cell division events that occur within

an expected ‘‘division window’’ defined by these variances.

From this, the author concludes that it is not evident that aging

occurs in these cells.

This conclusion, however, overlooks two critical factors.

First, by analyzing a large number of cell divisions (about

35000), we were able to show that the old pole cells are stati-

stically significantly biased (P< 0.00001)(2) toward a shorter

division length and a longer division time compared to the

actual population distribution. Second, these old pole cells

cumulatively grow more slowly (Fig. 3 of Ref. 2), divide at

shorter lengths, and take longer to divide as they continue to

reproduce. This is clearly not a sustainable situation for the

cell; even if the division times and lengths happen to fall within

a particular window of distributions, the cell is continually get-

ting slower and shorter at each consecutive old pole division.

In summary, it is a logical fallacy to conclude that, because

certain values fall within a window of variability, there is no

signal present. If this were the case, epidemiologists, for

example, would not be able to identify the risk factors for

disease among the enormous variability of the human popu-

lation. The fact that the physical parameters that we have

observed are consistently biased compared to the overall

population reveals that there is a signal hidden within the

apparent noise. This is perhapsmost intuitively revealed in the

lineage shown in Fig. 2 of Ref. 2, where the small effects on

growth rate result in an easily visible pattern of slowly growing

old pole cells. Based on the results summarized here and

described in Ref. 2, we conclude that E. coli is indeed

aging. As Woldringh noted, it is difficult to imagine a priori

the mechanisms that might be responsible for this; however,

our ongoing research has enabled us to preliminarily identify

one such process, which we are in the process of verifying and

quantifying.

References1. Woldringh CL. 2005. Is Escherichia coli getting old? BioEssays 27:

770–774.

2. Stewart EJ, Madden R, Paul G, Taddei F. 2005. Aging and death in an

organism that reproduces by morphologically symmetric division. PLoS

Biol 3:e45.

3. Koch AL, Schaechter M. 1962. A model for statistics of the cell division

process. J Gen Microbiol 29:435–454.

Eric StewartFrancois TaddeiInserm, U571

Univ. Paris 5

Paris, F-75015, France

E-mail: estewar1@post.harvard.edu

DOI 10.1002/bies.20295

Published online in Wiley InterScience (www.interscience.wiley.com).

BioEssays 27:983, � 2005 Wiley Periodicals, Inc. BioEssays 27.9 983

Correspondence