The Longevity of Naked Mole Rats

With increased technology and advancements in the medical field, the average human life expectancy is on the rise. Compared to the start of the 20th century, life expectancy at birth has increased from 47 to 79 years, a jump of nearly 70 percent. However, along with aging comes associated issues of bodily deterioration and age-based diseases. As these issues become commonplace, the search for treatments ramps up. But what if it was possible to find a solution to the root issue of aging? Meet the naked mole rat: a blind and fleshy hairless creature with horrific buck teeth and translucent, wrinkly, yellow skin. Despite their unsightly appearances, naked mole rats have a superpower: they don’t age.

Naked mole rats aren’t exactly immortal beings, but they do not follow the normal aging conventions that restrict all other mammals. The Gompertz Makeham law of mortality by Benjamin Gompertz, a British mathematician from the 19th century, proposes that the rate of human death increases exponentially with growing age, doubling every eight years after reaching 30. Even with the various factors that occur, this general trend still remains in society. Intuitively, this trend holds for all mammals but naked mole rats. Rochelle Buffenstein, a research professor currently at the University of Illinois, did extensive research regarding the lifespan of these fascinating rodents. In a study done at Calico Life Sciences, the daily mortality rate of naked mole rats stayed relatively constant at around one in 10,000 throughout their entire lives. Unsurprisingly, naked mole rats also live significantly longer than other rodent counterparts. For reference, rodents generally live a couple of years at most. Common mice live for no more than five years, while beavers and squirrels live up to 20 years. However, these numbers are trumped by that of the naked mole rat, whose lifespan can be upwards of three decades.

In addition to their amazing aging properties, naked mole rats are free from the natural problems associated with getting old: age-associated disorders. As healthcare, nutrition, and new technology increase life expectancy, it is no surprise that the leading causes of death for humans are related to factors stemming from old age. In America, the leading cause of death in 2019 was heart disease, followed by dementia. Lung cancer took the fifth spot, with a majority of the remaining deaths being attributed to organ-related diseases. The root biological process that causes these afflictions is called senescence, which refers to the deterioration of a living organism’s body. As all living organisms age, they experience this decline in both a cellular and physical ways. Cellular senescence is a self-defense mechanism for organisms where cells are restricted from proliferating. This allows for the body to prevent rising issues, such as tumors and mutations, that may be reproduced from these cells. However, this also stunts the cell, making it impossible to repair itself. As senescent cells become more common in a body, they inadvertently cause known age-associated disorders. For example, senescent tumor cells, which are meant to combat tumor proliferation, ironically play a huge part in cancer progression. The reason naked mole rats are able to maintain “agelessness” is the same reason they show this lack of deterioration across their body.

Clearly, humans stand a lot to gain in studying what methods naked mole rats utilize. Of course, there is no one solution that can be attributed to the naked mole rat’s success. Multiple factors contribute to their complexity and amazingness. Firstly, the mole rats have a very efficient method of responding to damages in the DNA replication. What makes their system of repair unique is the overexpression of glycosylases, which play a role in recognizing mistakes in the sequences. Due to the huge amount of this substance in a mole rat's body, they are able to label DNA errors significantly faster compared to humans.

In addition to their outstanding repair system, their blood contains higher levels of antioxidants, which combat the effects of oxidative stress. Oxidative stress occurs when there is a lack of antioxidants to balance out free radicals (instability-causing molecules) formed in the body. Free radicals are the reason behind basic changes that come with aging such as wrinkles, worsened eyesight, dementia, and other chronic health issues, including cancer.

Moreover, naked mole rats hold an abundant amount of various proteins that help in preventing deterioration, two of which are p53 and NRF2, which regulate proliferation and antioxidants respectively. Last but not least, as mentioned before, the deterioration that normally occurs from senescence does not occur in naked mole rats. While naked mole rats do experience cellular senescence, unlike other mammals, they are able to spontaneously destroy senescent cells without the involvement of the immune system. This prevents the accumulation of such cells and in turn, the age-associated disorders that follow.

These traits undoubtedly make naked mole rats an awesome role model for aging and present the solution to a multitude of human disorders. By understanding the methods they implement, there are countless possibilities surrounding gene-based therapies or drugs that replicate specific gene functions. If successfully imitated, humans can gain a treatment, if not cure, for most age-related ailments, drastically decreasing mortality rates.

However, there are still clear limitations to this research. While these mole rats do provide a model to follow, that's all they are: a model. It is questionable if humans can even recreate the various methods, as naked mole rats are vastly different creatures in appearance, environment, and physiology. Something that works for them might not work for us, as efficiently, or at all. The long lifespan of naked mole rats makes it difficult to obtain multiple data points and a sufficient amount is needed for any type of data collection. Humans are not going to stop aging anytime soon, and the research for these “miracle drugs” will take a while to even take off the ground. But until then, the naked mole rat definitely presents a promising start to this journey for youth.