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Bacteria once thought immortal do in fact age, a fact discovered fairly recently. In essence, a bacterium seems to push off more of its biochemical damage onto the "older" of the two new daughter bacteria created when it divides. Aging, recall, is defined as the accumulation of biochemical damage - that "older" daughter bacterium is "older" because it is more damaged.
So, while interesting, why should we care about all this? What is the relevance of this asymmetrical division process to aging in multicelled organisms, or the relevance to age-related degeneration in humans? A few strands of research are touched on in a recent PNAS paper:
Aging is a fundamental characteristic of all living organisms. Recent work in our laboratory has identified and quantified aging in Escherichia coli, where cells progressively decline in growth rate and reproductive ability with increasing cell pole age, establishing this organism as a simple experimental model of aging.
In this outwardly symmetrically dividing bacterium, the cell inheriting the old pole after division grows more slowly and divides less frequently, therefore exhibiting aging. Thus, the dividing cell partitions its resources and/or damaged components in a biased fashion, leading to differential growth potential distinguishing the old-pole aging cell and its young-pole counterpart.
To shed light on the molecular mechanism underlying aging in E. coli, we focus here on the partitioning of damaged, aggregated proteins in wild-type bacterial cells growing in a nonstressing favorable environment.
Aggregated proteins are linked to cellular degeneracy in many age-related diseases [e.g., Huntington's disease, Alzheimer's disease, spongiform encephalopathies, Parkinson's disease, and cataracts]. In addition, numerous reports link protein maintenance and repair functions (e.g., folding and disaggregation-related chaperones and proteases) to aging. Consequently, considerable effort has been invested in the study of protein aggregation, resulting in a better understanding of aggregation in vitro and in the identification of a number of genes involved in this process, many of which are widely conserved in all kingdoms of life. In contrast, less is known about the aggregation process in vivo, its causes, and its direct consequences on cell fate; such understanding has been hindered by the inability to follow in vivo the formation and outcome of inclusion bodies under native conditions.
Advances in biotechnology make these and many other complex projects possible. The researchers found that, as expected, "old pole" bacteria retain more of the damaging protein aggregates than "young pole" bacteria. It seems likely that bacterium-by-bacterium analysis of other measures of damage will show similar results.
As the paper notes, there are all sorts of similarities between asymmetric division in bacteria and related processes in our cells:
Intriguing is the similarity between aggrosome localization to the eukaryotic centrosome and the inclusion bodies to the bacterial division plane. In the former model, putative stem cells exhibited a lower aggregation level as compared with differentiated cells. It remains to be seen whether, as in bacteria, germ-line cells use the same mechanism to ensure their optimal survival. Is the unknown segregation mechanism common across kingdoms? Is the bacterial mechanism a precursor (possibly "passive," e.g., non-energy consuming?) mechanism or rather evolutionarily converged to the same optimal solution?
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although cells can potentially invest more in maintenance and repair during growth phase, this may not be cost-effective, prevailing in cycles of aging and rejuvenation by damage segregation. Interestingly, in terminally differentiated postmitotic cells such as neurons, aggregate accumulation correlates with diseases. Because all organisms face challenges of protein folding and aggregation, it is unsurprising that the genes coding for the machinery for protein folding quality control are highly conserved across the domains of life. Given the newly apparent universality, E. coli may provide a powerful system for studying the formation and prevention of toxic aggregates, such as those responsible for a number of degenerative diseases.
At the end of this road may be methodologies for rejuvenating cell populations, such as aging stem cells, through manipulating the processes of asymmetric division - passing off biochemical damage to a daughter population that is then discarded. Or not. As Aubrey de Grey points out, these experiments really should be repeated in cell populations or single-celled organisms before we get too excited - there are, after all, significant differences between a cell and a bacterium.
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Posted by Reason
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