Fascination with aging is hardly a recent phenomenon. Among the very first written works, “The Epic of Gilgamesh” 1800 BCE, describes a Sumerian king in search of immortality. Recently, aging research has grown rapidly with the goal of investigating the causes of aging to develop therapies that can reverse the predictable decline in health and vitality. When we look to nature, examples abound of long-lived species that break the rules, for example the Bowhead whale can live for over 200 years, the Greenland shark for over 400 years, and the quahog clam can live to over 500 years. This doesn’t even address the plant kingdom where trees like the sequoia live for over 2000 years. Investigation into many of these long-lived outliers in nature have provided valuable insight into our deepest questions about aging.
When looking at the animal kingdom, it becomes apparent that lifespan is extremely variable. Worms live only a few weeks, flies a few months, mice a couple years, chimps a few decades, and Bowhead whales a few centuries. The simplest observation is that large animals tend to live longer than smaller animals in general. It is also true that smaller animals have elevated metabolisms. This data led to the idea that an elevated metabolism induces premature mortality while a slow metabolism can increase lifespan. Although, this provided a nice lens in which to view aging across species it quickly become too filled with exceptions to be seen as the universal cause. For example, both the opossum and the kangaroo have a relatively slow metabolism but still only a short lifespan of 2 and 6 years in the wild, respectively. Other outliers like birds and bats live exceptionally long and do not fit into the curve, nor do naked mole rats, primates, and bowhead whales just to name a few.
In truth, these very interesting long-lived outliers on the body mass lifespan chart draw the attention of scientists. Perhaps these outliers in nature held answers about how to live longer? First, it seems like evading predation is an important step to developing into a long-lived outlier species. The birds and bats can fly away, the naked mole rat can burrow, and the whale becomes too big to be eaten by most predators. It is in cases where selective pressure is removed at an early stage by predation that longevity mechanisms have an opportunity to emerge thru evolution. In the case of Brandt’s bat it had been noted that they rarely die in the wild due to age related causes. This is perhaps due to the fact that their telomeres do not shrink as they age. Normally, telomeres act as a protective cap at the end of our DNA to prevent DNA damage and eventual cell death. Interestingly, Brandt’s bats are able to maintain telomere length without expressing telomerase, the enzyme responsible for telomere maintenance.
Another fascinating outlier is the naked mole rat which can live to be 30 years old, about 10 times longer than predicted based on its size. Scientists at the University of Rochester discovered that naked mole rat produces a specific type of hyaluronic acid which prevents cancer. They, along with the 500 year old quahog clams are also extremely good at making error free proteins. The elephant, another long lived species has an extra copy of p53 which is important for tumor suppression. These examples demonstrate the many ways that various species have evolved in order to escape a short life providing many novel molecular targets to potentially increase lifespan.
Altogether, the longest living species found in nature are providing valuable information that demonstrate the complexity of biological aging. At first glance, it might appear as if these species have developed several unrelated mechanisms to live longer, but the truth is that each is addressing one critical driver of aging in a specific way. There has been a recent explosion in the development of anti-aging strategies to enhance longevity. Perhaps most excitingly, research in this area reveals that although aging is complex, it is also malleable and can be tackled from multiple angles. Finally, reverse engineering is always easier than creating something completely new and therefore in the case of long-lived species, nature might be providing a blueprint for the development of future aging therapies in hopes of treating age related diseases.
Writing by: Patrick Paine.