Any organism that lives, grows and reproduces must also age. People often think of aging in the physical sense-gray hair, slowed movements and wrinkles-but aging fundamentally occurs on a molecular level, inside of cells. As organisms age, their cells accumulate damage that impairs functioning. Molecular damage is implicated in many age-related conditions in humans and is equally relevant for single-celled organisms. While they may not 'look' their age, bacteria feel the passage of time too.
Binary Fission: The Key to Immortality?
Bacteria differ from us in many ways, including in their modes of growth and reproduction. Unlike humans and other animals, single-celled organisms, such as bacteria and some fungi, can undergo a process called binary fission to reproduce, meaning that they duplicate their DNA and then split in 2. Replication via binary fission can be very fast-the fastest-growing bacterium we know of can divide in less than 10 minutes!
Considering our very different ways of life, it might seem difficult to apply the concept of aging to bacteria. Indeed, it was long thought that bacteria and other organisms that reproduce via binary fission do not age at all. This was because binary fission was thought to be a symmetrical division, producing a parent and offspring identical in age, thus leading to a what scientists called 'functional immortality' for the population. On the other hand, asymmetric division, whereby the parent is older than the offspring, was thought to be required for an organism to be able to age at all.
Evidence against the accepted immortality paradigm first came in 2005, when scientists showed that Escherichia coli actually exhibits differences between 'old' and 'new' in parent and offspring cells, respectively. By following dividing cells with a microscope, the researchers could show that the older cells' growth rate and offspring production decline over time, and that they die more frequently than their younger offspring cells. Thus, despite looking the same, the cells undergo divisions that leave them functionally asymmetric, causing cells to age over time.
Asymmetric Division Does Damage Control
Using mathematical models and data from the 2005 study, other scientists later showed that asymmetry is important for the whole population, as it elevates the population's fitness by maintaining variance. Variance is what natural selection acts upon, and more variation in a population generally equates with a better chance of survival in changeable conditions. This study was important for reconciling previously conflicting views about bacterial aging and showing how important aging can be on an evolutionary level.
But how does asymmetric division help to keep populations fit? Part of the answer lies in protein aggregation, a contributor to aging in both bacteria and eukaryotic cells. Protein aggregation is implicated in many age-related diseases in humans, including Alzheimer's and Parkinson's, as these aggregates can be toxic and cause cells to die. Proteins also aggregate in E. coli, as researchers showed using fluorescent molecules that attach to aggregates, but are cleverly dealt with to minimize damage. As a feature of asymmetric division, older cells accumulate proteins to segregate the age-related damage, keeping their offspring looking 'younger,' molecularly speaking.
Stress Ages Bacteria and Humans Alike
Stress is another factor that is thought to contribute to aging in humans, and a 2024 paper suggests that the same is true for our bacterial companion, E. coli. Like any kind of cells, E. coli cells accumulate mutations throughout their lifetimes. Some of these mutations may be nonlethal but still negatively impact the cell's fitness, for example, causing an important protein to lose its function. Such deleterious loss-of-function mutations can kickstart a stress state inside the cell that ultimately helps it to survive the mutation.
The researchers analyzed the effects of over 60 different nonlethal loss-of-function mutations in E. coli, focusing on mutants with non-functional ATP synthases, large protein complexes that allow cells to generate energy in the form of ATP. These mutants were found to increase their metabolic activity to compensate for the mutation, which comes at a cost-they grow slower, and some enter a purgatory-like, 'postreplicative' state faster than non-mutants, especially if their surroundings are nutrient-poor.
Considering their findings, the researchers suggested that there is an "aging cost" that comes with maintaining resistance to stress on a population level. Besides shedding light on a potentially ancient mechanism of aging, the factors that contribute bacterial aging could be investigated as new antibiotic targets. Additionally, some human diseases are also perpetuated through cellular stress states, and understanding how these work on a molecular level could lead to development of new treatments.
Time waits for no one, not even bacteria-and that's a good thing. Far from immortal beings beyond the reaches of aging, bacteria are an interesting system in which to study the molecular mechanisms that contribute to age-related decline. Their rapid and robust growth means we can observe many generations in a relatively short experiment and test the effects of all kinds of environmental and genetic factors on the complex process of aging. We still have much to learn about aging, but we are in good company on the journey.
Want to learn more about how studying old bacteria can shed light on the aging process in other organisms? On this episode of "microTalk," join Steve Finkel, Ph.D., who studies the Growth Advantage in Stationary Phase (GASP) phenotype, to hear how carbohydrate modifications in old bacteria can help illuminate diabetes and small differences in bacterial growth conditions can result in huge differences in bacterial physiology.
