Bacterial Responses to Damage Provide Insight into the Ancient Origins of Aging

Aging is an accumulation of molecular damage and its consequences. Even single-celled life such as bacteria ages, quite differently from complex multicellular organisms, of course, but nonetheless in a way that is determined by strategies for coping with damage accumulation. Observing bacteria can provide insight into the ancient evolutionary origins of aging: why it exists, and how aging in single-celled life set down the foundations for aging in multicellular life.

Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable patterns of mortality and immortality. Through single-cell microscopy and microfluidic techniques, we find that these patterns are explained by the dynamics of damage accumulation and asymmetric partitioning between daughter cells.

Experimental data from long-term microscopy of bacterial lineages revealed that, in the presence of intracellular damage, each cellular division produces two physiologically asymmetric daughters. This asymmetry is generated because the damage harbored by the mother is biased toward the old cell pole, causing the daughter that inherits this pole - termed the old daughter - to age. Its sibling, on the other hand, rejuvenates through the inheritance of a lower damage load, being called the new daughter. Therefore, by partitioning damage with asymmetry, bacterial populations engage in a trade-off in which the fast growth of new daughters is sustained at the expense of the declining cellular function of old daughters.

At low damage accumulation rates, both aging and rejuvenating lineages retain immortality by reaching their respective states of physiological equilibrium. We show that both asymmetry and equilibrium are present in repair mutants lacking certain repair chaperones, suggesting that intact repair capacity is not essential for immortal proliferation. We show that this growth equilibrium, however, is displaced by extrinsic damage in a dosage-dependent response. Moreover, we demonstrate that aging lineages become mortal when damage accumulation rates surpass a threshold, whereas rejuvenating lineages within the same population remain immortal. Thus, the processes of damage accumulation and partitioning through asymmetric cell division are essential in the determination of proliferative mortality and immortality in bacterial populations. This study provides further evidence for the characterization of cellular aging as a general process, affecting prokaryotes and eukaryotes alike and according to similar evolutionary constraints.

Link: https://doi.org/10.1371/journal.pbio.3000266

Comments

Is this damage accumulation / asymmetric partitioning process present in mitochondria?

Posted by: Antonio at May 31st, 2019 6:47 AM

It should be otherwise we would have run out of immortal mitochondria even before we turned multicellular...

Posted by: Cuberat at May 31st, 2019 8:31 AM

Very interesting. You'd think this doesn't restrict multicellular life from immortality, given our stem cells can also assymmetrically partition damage. Perhaps a pleitrophic explanation would solve this riddle; giving too much damage to the somatic line might compromise organism viability, hence aging of the stem cell line.

Mitochondria are more than capable of fully maintaining health, that they don't is likely a similar trade off, I.e. putting short term ATP production above the long term requirement for fission and lysosome disposal of faulty mtDNA loops.

Posted by: Mark at June 2nd, 2019 4:29 AM

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