When did aging first evolve?
We know that several aspects of aging are conserved across the animal kingdom, implying that the progenitor of metazoans already suffered from aging. Animals even share some features of cellular aging with single-celled species such as yeast, pushing the evolutionary origins of aging back to the first eukaryotes.
But what about bacteria? At first, the question seems ridiculous: bacteria are physiologically immortal, and except for some weirdos like Caulobacter, they divide symmetrically. If a bacterial species aged, eventually every lineage of that species would die out.
Not so fast: it turns out that bacteria only look like they divide symmetrically. To illustrate this point in a simple way, let’s consider a bacillus like everyone’s favorite laboratory workhorse, E. coli. The cell is rod-shaped, with a pole at each end. The cell divides by forming a septum right in the middle, in the process synthesizing two new poles — so each daughter has an old pole and a new pole (see panel a in the figure below). So far so good, but in the next generation, each of those old poles has to be passed on to a granddaughter, and then a great-granddaughter, all the while getting older…and older…and older.
The poles are where unwanted cellular trash (like aggregates of damaged proteins) builds up, and this garbage accumulates with every generation. In yeast and even human stem cells, asymmetric damage partitioning is one way that immortal cell lineages stay immortal: by restricting the gunk to one daughter cell, the other daughter is born damage-free. But this rejuvenation comes at a cost: over a series of divisions, the cell that winds up holding the short straw starts to lose viability, and eventually becomes unable to divide at all.
This process has been known for quite a while to happen in bacteria, but it remains unclear whether it represented aging per se. Previously, however, the data were equivocal on the question of whether the accumulated damage was in any way harmful, or instead just a harmless feature of having been around a long time, like a well-worn, ugly hat.
But recent paper from Lin Chao’s lab at UCSD’s Division of Biological Sciences showed that the unequal inheritance of damage in bacteria results in an age-structured population in which different groups of cells have different physiological properties — a hallmark of cellular aging.
The researchers used microfluidic devices and single-cell imaging to track the lineages of bacteria as they divided, carefully monitoring the fate of “old” poles and their effect on cell growth. By cleverly manipulating the structure of the microfluidic devices they used, the authors ruled out several kinds of experimental artifact, including the possibility that some old bacteria were simply starving or suffering from some kind of extrinsic damage.
Collectively, the results showed that bacteria do indeed suffer from intrinsic aging.
Notably, however, the outcome of this type of aging was not loss of viability, but rather a separate equilibrium state in which “old” lineages divide more slowly than “young” lineages. Of course, when you’re a bacterium, slowed growth can be tantamount to extinction: by the relentless logic of exponential growth, a lineage with a longer division time will eventually be outcompeted by faster-growing clones. Moreover, in the real world, extrinsic damage and other kinds of stress could drive growth rate or cellular viability down even further.
The upshot of this is a strong indication that aging (or at least one key aspect of cellular aging) is evolutionarily ancient, nearly as old as prokaryotic life itself. This makes sense: in the early days of life on Earth, a species unable to selectively partition damage would never enjoy the growth boost that followed rejuvenation, and would eventually lose out to competitors that discovered this trick.
As the authors of the study conclude:
The identification of deterministic divisional asymmtry in bacteria…could characterize aging at the cellular level as a ubiquitous process in living organisms. … Taking these notions together, bacteria could serve as a model for the evolutionary origins of aging, providing quantifiable long-term data on cellular aging and rejuvenation. Although aging in bacteria and traditional organisms will always have their differences, it may be that some key features of biological aging arose with the first microbes.
Obviously, bacterial aren’t animals, but given that a key feature of cellular aging appears to be conserved across domains of life, we can imaging using forward and reverse genetic screens in bacteria—with all the advantages of rapid division time, experimental tractability, and low cost—to reveal the molecular details underlying asymmetric damage partitioning.
Proenca et al. “Age structure landscapes emerge from the equilibrium between aging and rejuvenation in bacterial populations.” Nature Communications 13 September 2018 • DOI