Forever Young? The Naked Mole Rat Teaches Scientists About Longevity

(Posted on Monday, December 18, 2023)

Can the humble naked mole rat help us extend our life span? Researchers at the University of Rochester think so. Their latest findings, published in the journal Nature, provide convincing proof of principle: transferring a gene from naked mole rats into ordinary mice helps extend their lives by almost five percent. The mice also enjoyed improved health in the later stages of their life. 

No Fur, But Plenty of Life

Compared to other rodents, naked mole rats have unprecedented longevity; their average lifespan lies somewhere between 10 to 30 years. For comparison, most similarly sized rodents are lucky if they make it to four. This feat has made the naked mole rat very popular amongst scientists who study longevity. 

Not only are they long-lived, but they are also unusually healthy. Whereas other rodents, like mice and rats, are susceptible to many of the same age-related diseases that we are —cardiovascular disease, cognitive decline, and cancers— naked mole rats are largely impervious. Indeed, they can generate new neurons for up to two decades after birth and, over this same period, there are no noticeable changes to cardiovascular function, bone quality, or metabolism, all of which usually deteriorate with age. 

This “eternal youth” is mirrored at the cellular level. Structures called telomeres, found at the ends of chromosomes, protect our DNA from damage — they act as a cap, a little like the plastic cap at the end of a shoelace. These normally shorten with age, causing all kinds of knock-on effects (none of them good). But not so in the naked mole rat. Instead, their telomeres elongate slightly as they age. They also don’t face any issues with proteasome function. Think of the proteasome as the cellular garbage disposal system: it gets rid of old and damaged proteins that are clogging up the space. Degradation of these proteins is vital to the smooth operation of many cellular processes. 

So, what’s behind the mysteriously long and healthy life span of these hairless critters? 

Hyaluronic Acid: The Elixir of Life?

Hyaluronic acid is a chief component of the extracellular matrix, a kind of glue or scaffolding that provides mechanical support to cells and is involved in a host of important cellular functions, including cell migration and proliferation. Hyaluronic acid comes in different masses, which define its function. The low-mass version of the molecule (LMM-HA) has been associated with inflammation and cancer metastasis. The high-mass version (HMM-HA), on the other hand, has anti-inflammatory properties and helps keep the body’s tissues in order. 

Vera Gorbunova and Andrei Seluanov, the two senior authors of this study, had previously discovered that naked mole rats have up to ten times more high-molecular-mass hyaluronic acid in their bodies than do their close relatives, mice, or even us humans. On top of having more of it, the hyaluronic acid produced by the mole rats also seems to be particularly good at protecting cells against harmful agents. In fact, high hyaluronic acid levels are integral to the naked mole rat’s resistance to cancer: removing the acid from the cells of naked mole rats makes them significantly more susceptible to the formation of cancerous tumors. 

Given the anti-cancer and anti-inflammatory effects of the mole rat’s hyaluronan, the researchers set out to establish whether the benefits could be transferred to other rodents. They genetically modified mice so that they carried the naked mole rat version of the gene that produces the acid, hyaluronan synthase 2 gene. 

Next, they studied these mice for the duration of their lifespan, paying special attention to cancer incidence. A group of non-genetically-modified mice acted as a control. Whereas 70% of the mice in the control group died of cancer, only 57% of those with the mole-rat gene died of cancer. This difference was most pronounced in the oldest mice, aged 27 months and onward: here, 83% of the control group suffered from cancer, whereas only 49% of those with the mole-rat version of the hyaluronan synthase 2 gene ended up with cancer. 

Resistance against “spontaneous” cancer incidence was mirrored by a similar resistance against chemically “induced” cancer incidence. 

The group of mice with the mole-rat version of the gene also lived longer than their counterparts and enjoyed fewer health issues as they aged. Crucially, low-level chronic inflammation —sometimes referred to as “inflammaging”— was markedly lower in the modified mice than in those with the normal version of the gene. 

Takeaways

Although we are still a long way from harnessing the findings of this study toward human longevity, they act as a convincing proof of principle that the same mechanisms that allow naked mole rats to live such long and healthy lives can be recreated, or transferred, to other rodents. In time, we may be able to transfer them to humans as well. 

This article was originally published on Forbes and can be read online here.