Fight Aging!

There is a portion of the life science community interested in the longevity of plants, though it is fairly disconnected from research into medicine and aging for the animal half of the planet. We can debate whether or not there is anything useful for medical research to be learned from comparing plant species and gaining a better understanding as to why some are much longer-lived than others. After all, researchers already reach for very difference species when beginning investigations of cellular biology relevant to medicine. In the animal-focused aging research familiar to this audience, a great deal of experimentation and exploration is carried out in studies of yeast, a fungus rather than an animal, and yet possessing so many similarities to mammals in its cellular processes that the data can be very useful. Yeast is a long evolutionary distance from humanity, but it is arguably a bigger leap from yeast to plants than it is from humans to yeast. Plants have chloroplasts, and that's just the start of a long list of differences. Early stage research into cellular biochemistry is always a trade-off: much more can be done for a given amount of funding in yeast, flies, and worms, but many of those results will fail to also prove relevant in mice, let alone in humans. So far the collective wisdom of the life science research community has declared that yeast passes the cost-benefit equation, while anything with a chloroplast does not.

There are of course, always heretics willing to argue the point, but that is the way science progresses. In the research noted here, a stem cell angle is pursued, and this is one of the areas where I could perhaps be persuaded there might be something useful to be learned from plant life science. If investigations of hydra and their continuous regeneration - and how that relates to mammalian stem cell biology - are worthwhile, then so might be research into the continuous regeneration of some plant species. Still, this is about as close to fundamental research as one can get, which means it is a part of the long-term gathering of information, with no presently plausible application to medical science, and we can only speculate as to where any part of it might prove useful in the decades ahead.

Mechanism Behind Extreme Longevity in Some Plants

Compared to humans' century-long life span, some plants - evergreens in particular - have the capacity to live for an exceptionally long time, even millennia. Researchers zeroed in the formation of axillary meristems - stem cells that give rise to branches - in Arabidopsis thaliana and tomato, finding few cell divisions between the apical meristem located at the very top of a plant and the axillary meristems. With such little proliferation comes less opportunity to accumulate potentially deleterious genetic mutations in somatic cells that could kill the organism, the authors reasoned. "Meristem aging is not a problem for perennial plants, in other words. The meristems are the growing units. If they don't senesce, then the plant will keep the capacity to grow and reproduce forever, at least potentially." Instead, structural defects or pathogens most often kill plants.

In tomato, "it turns out all the cells around are making lots of cell divisions to make leaves and stems, but few cells are destined to become the axillary meristem. Those really don't divide." If the same is true in other species, the results suggest that most plants have something akin to the germline in animals. "That is, plants seem to set aside some cells in such a way as to minimise the number of mutations they accumulate."

One project underway in Switzerland could lend empirical data to test the group's hypothesis. The Napoleome project is an effort to sequence the full genome of a 238-year-old oak tree. The team has actually sequenced two genomes, taken from different parts of the tree, to see how many mutations are present and whether these distant sites share any mutations. "This meristem hypothesis is what we're testing basically with our project. No one has an idea of how many somatic mutations are in an old tree that has lived outside for more than 200 years." Whether this mechanism to limit somatic mutations was selected for evolutionarily to increase longevity or protect the germline "remains an open question, and one that would be very tricky to answer."

Patterns of Stem Cell Divisions Contribute to Plant Longevity

The lifespan of plants ranges from a few weeks in annuals to thousands of years in trees. It is hard to explain such extreme longevity considering that DNA replication errors inevitably cause mutations. Without purging through meiotic recombination, the accumulation of somatic mutations will eventually result in mutational meltdown, a phenomenon known as Muller's ratchet. Nevertheless, the lifespan of trees is limited more often by incidental disease or structural damage than by genetic aging. The key determinants of tree architecture are the axillary meristems, which form in the axils of leaves and grow out to form branches. The number of branches is low in annual plants, but in perennial plants iterative branching can result in thousands of terminal branches.

Here, we use stem cell ablation and quantitative cell-lineage analysis to show that axillary meristems are set aside early, analogous to the metazoan germline. While neighboring cells divide vigorously, axillary meristem precursors maintain a quiescent state, with only 7-9 cell divisions occurring between the apical and axillary meristem. During iterative branching, the number of branches increases exponentially, while the number of cell divisions increases linearly. Moreover, computational modeling shows that stem cell arrangement and positioning of axillary meristems distribute somatic mutations around the main shoot, preventing their fixation and maximizing genetic heterogeneity. These features slow down Muller's ratchet and thereby extend lifespan.