Fight Aging!

The paper I'll share today takes a look at stem cells over the course of aging in different sea urchin species that exhibit radically different life spans, ranging from a few years to somewhere north of a century. A fair number of marine species, some urchins included, are negligibly senescent, meaning that they show few signs of degeneration or increased mortality due to intrinsic causes until very close to natural death. In some cases it has been impossible to measure life span in a random sample gathered from the ocean, as was true for lobsters until recently, and that combined with the paucity of funding for investigating the aging of sea life has meant that the research community has no good, certain data for the maximum life span of many of these species.

When looking at lower life forms that appear to be ageless or very close to ageless, such as hydra, a common theme is hyperactive, proficient, constant regeneration of all tissues. Since distinct populations of stem cells serve this purpose in hydra and higher species, both those that are negligibly senescent and those that age gracelessly, it makes sense to gain a better understanding of how stem cell biology differs between those who age and those who age less. This isn't just longer lives versus shorter lives, but perhaps more importantly how much of an age-related decline occurs across the life span. There are also other compelling reasons for such an investigation, such as the differences between salamanders, capable of regrowing limbs and organs, and mammals, who cannot. That may be somewhat orthogonal to the question of how stem cell biology affects aging, since it is debatable as whether or not salamanders are negligibly senescent. This isn't a classification with a clear dividing line, and many species are happy to occupy the large grey area. Still, that is a problem solved by gathering more data, and by gaining more knowledge - and thus at root by funding more research.

In our species, and most others of interest, stem cell activity declines with age. The conventional wisdom, not unchallenged, is that this serves to give us additional time free from cancer at the expense of a loss of tissue maintenance, producing growing frailty and increasing organ failure. Damaged cells undertaking activity raise the risk of cancer. If those cells instead remain quiescent, there is less of a risk. In the view of aging as an accumulation of cell and tissue damage, stem cells shut down in response to rising levels of damage. But how does this all work in negligibly senescent species, and - as ever - how might the research community port over some of those benefits into our biochemistry in a cost-effective manner? For my money, I'd guess that this line of development is destined to be lengthy and expensive, but that is the way of most research. The better path as I see it is to repair the damage that causes stem cells to react by retreating from their work, and to replace those stem cell populations wholesale where the cells have themselves become damaged. The present stem cell industry is a good first step on that road, but there is much more yet to be done to reach the desired endpoint.

Is aging inevitable? Not necessarily for sea urchins

Sea urchins are remarkable organisms. They can quickly regrow damaged spines and feet. Some species also live to extraordinary old ages and - even more remarkably - do so with no signs of poor health, such as a decline in regenerative capacity or an increase in age-related mortality. Researchers study the regenerative capacity of sea urchins in hopes that a deeper understanding of the process of regeneration, which governs the regeneration of aging tissues as well as lost or damaged body parts, will lead to a deeper understanding of the aging process in humans, with whom sea urchins share a close genetic relationship.

Researchers studied regenerative capacity in three species of sea urchins with long, intermediate and short life expectancies: the red sea urchin, Mesocentrotus franciscanus, one of the world's longest-lived organisms with a life expectancy of more than 100 years; the purple sea urchin, Strongylocentrotus purpuratus, with a life expectancy of more than 50 years; and the variegated sea urchin, Lytechinus variegatus, with a life expectancy of only four years. The scientists hypothesized that the regenerative capacity of the species with shorter life expectancies would decline as they aged. Much to their surprise, however, they found that regenerative capacity was not affected by age: as with the very long-lived sea urchin, the regenerative capacity of the species with a shorter life expectancy did not decline with age. "We wanted to find out why the species with short and intermediate life expectancies aged and the long-lived species didn't. But what we found is that aging is not inevitable: sea urchins don't appear to age, even when they are short-lived. Because these findings were unexpected in light of the prevailing theories about the evolution of aging, we may have to rethink theories on why aging occurs."

Maintenance of somatic tissue regeneration with age in short- and long-lived species of sea urchins

Sea urchins exhibit continued growth and reproduction throughout their lives and yet different species are reported to have vastly different life expectancies in the wild. The proper balance of cell division and cell death is important for life-long growth and homeostasis and maintaining this balance with age would be essential to achieve negligible senescence, whereas failure to maintain this balance would promote aging and shortened lifespan. In this study, cell proliferation was measured using in vivo incorporation of 5-bromo-2′-deoxyuridine (BrdU).

It was determined that there was a low level of BrdU incorporation and apoptosis in the internal tissues of three species of sea urchins with different lifespans, regardless of age. The low levels of cell proliferation are consistent with the low metabolic rates that have been reported for sea urchins, and suggest that unlike Hydra, sea urchins do not avoid senescence by continually replenishing tissues at a high rate. As expected for animals that grow indeterminately, there were higher levels of cell proliferation compared to apoptosis in the tissues. The low levels of apoptosis in the tissues of young and old animals are consistent with low levels of cellular damage that does not increase with age. Interestingly, in L. variegatus and S. purpuratus, which have a ~ 10-fold difference in lifespan, there were few differences in the amount of cell proliferation and apoptosis in tissues compared within age categories.

To determine whether regenerative potential was maintained with age in sea urchins, the regrowth of amputated spines and tube feet was measured in L. variegatus and S. purpuratus. The data demonstrate that the regenerative potential of both types of appendages was maintained with age in these sea urchin species. A prediction from the evolutionary theories of aging is that level of extrinsic mortality influences the rate of aging, such that high levels of extrinsic mortality would be associated with tissue decline once an organism reaches reproductive maturity and survivorship in the wild becomes increasingly unlikely. L. variegatus is predicted to have a much lower annual survival rate than S. purpuratus and M. franciscanus and an estimated lifespan in the wild of about 4 years, and yet the results did not show evidence of decline in regenerative capacity in larger/older animals. It is possible that L. variegatus have the potential to live much longer than has been reported in the wild (and hence that the animals used in this study were not approaching their maximum lifespan potential), or that longevity in these animals is not limited by investment in (or capacity for) maintenance and repair of damaged tissues.

The lack of age-related differences in the maintenance of tissue homeostasis and regenerative potential in sea urchin species with different lifespans were unexpected in light of current evolutionary theories of aging, and further study is required to understand the factors underlying the short lifespan of L. variegatus in particular.