Scientists are Exploring Longevity Genes in Naked Mole Rats to Extend the Lifespan of Mice

• Transplanting a longevity gene from naked mole rats has proven to prolong the lifespan of mice. 

• This gene not only extends lifespan, but can potentially protect against malignant growths. 

• By exporting this longevity gene across species, researchers can potentially extend the lifespan of humans. 

This study was posted by ScienceDaily:

Naked mole rats have unique physiological properties that set them apart from other mammals.  

From near blindness, to their ability to thrive underground, and ectothermic metabolism that sustains body temperature via the external environment—these animals make for unique creatures. Perhaps the most distinct identifier, however, is the naked mole rat’s extended lifespan—these animals can live up to 41 years, a surprising feat for small rodents. 

Researchers at the University of Rochester, noting this longevity, experimented with isolating the gene responsible for the mole rat’s long life, and transferring it to mice.  

"Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals," says Vera Gorbunova, the Doris Johns Cherry Professor of Biology and Medicine at Rochester. 

In this article, we'll explore what research reveals about the health and lifespan effects of transplanting naked mole rat genes into mice.  

We'll also consider what this development might mean for elongating human lifespan. 

Unique Aging Mechanisms of Naked Mole Rats 

Naked mole rats enjoy a special longevity in the rodent kingdom. Where these animals can live up to four decades, counterparts like hamsters only live up to five years. Other animals like the Canadian beaver come close to the mole rat, with a lifespan extending up to 23 years, similar to the porcupine which can live for 27-28 years.   

Different aspects of the mole rat’s physiological and eusocial attributes contribute to its long life. 

For example, naked mole rats show exceptional immunity against uncontrolled tissue growths. Compared to other animals that experience a 20-46% death rate due to malignant growths, naked mole rats have evolved efficient mechanisms against these developments. 

In the past, researchers believed powerful cell resistance was responsible for the naked mole rats’ protection against growths and related illnesses. However, further studies reveal that the animal’s microenvironment—its cell structures and molecules surrounding each cell, plus the mole rat’s immune system nip malignant growths in the early stages—rather than provide instant resistance mechanisms against these conditions.  

Likewise, as burrowing creatures, naked mole rats have evolved highly effective methods for maximizing the limited oxygen available underground. By adapting to low oxygen levels, these animals are equipped with the ideal resources to thrive in a subterranean environment. 

While breathing, the mole rat’s oxygen intake can lead to oxidative stress, or the release of reactive oxygen species (ROS) in the mitochondria—the part of the cell responsible for energy production. Because mole rats adopt this practice from a young age, early exposure to oxidative stress can decrease stress-related aging, contributing to its longevity.  

Adding to the mole rat’s unique features is its low metabolic rate. These creatures require less energy to sustain their daily functions. This low rate may be tied to the need to manage limited food resources while underground.   

The mole rat’s DNA workings also contribute to its long life. With the DNA as one of the core features of each cell unit, expected wear and tear from environmental exposures like radiation, chemicals, and metabolic byproducts can damage this structure, leading to cell aging. Naked mole rats have developed effective DNA repair mechanisms to maintain cellular integrity, which can contribute to slowing the aging process. 

But at the core of the naked mole rat’s longevity are special molecules—high molecular weight hyaluronic acid (HMW-HA). Researchers previously discovered this compound as the mechanism responsible for the mole rat’s protection against life-threatening growths, and its high median lifespan. By separating this compound and transplanting it to other animals, scientists are testing out a potential alternative for extending individual lifetimes. 

How does the HMW-HA Compound Improve Lifespans? 

The HMW-HA gene is the potent force behind the naked mole rat’s longevity. In addition to increased lifespan, these molecules also regulate core functions that promote cognitive abilities, heart health, joint function, and support systems that typically degenerate with age.  

High molecular weight hyaluronic acid is a naturally occurring substance in the body. As proven in naked mole rats, this compound performs several functions and is noted for its ability to maintain moisture, lubrication, and tissue integrity.  

HMW-HA is tagged ‘high molecular weight’ because of the size of the hyaluronic acid molecules. The naked mole rat has larger molecular weights in comparison to human low molecular weight, or the rooster comb’s medium-weight molecular acid. 

As far as anti-aging properties go, HMW-HA packs a punch to delay the expected hallmarks of aging. This compound supports tissue stability and improves homeostasis. Its anti-inflammatory functions also help to maintain cell integrity, while the antimetastatic properties of HMW-HA prevent diseases in an organism from spreading between cells.  

HMW-HA can be isolated or modified for several purposes. In this study, researchers transferred the gene responsible for making this compound, to discover if the mole rat’s longevity could be exported to a mouse. 

Transferring a Gene that Produces HMW-HA to Mice 

Compared to the naked mole rat, the average lab rat can live for about 4.5 years. 

Researchers curious about extending the lifespan of these rodents genetically modified a mouse model to produce the naked mole rat version of the hyaluronan synthase 2 gene, which makes the protein that produces HMW-HA. 

Researchers found that mice enhanced with the naked mole rat longevity gene were better protected against growths and malignant skin cells. 

These mice also had improved health, and most importantly—lived longer than regular mice. 

When these enhanced mice aged, researchers found that they displayed fewer signs of inflammation in different parts of their bodies, a common indication of aging. These rodents also maintained a healthier gut compared to their regular counterparts. 

Lifespan Extension for Humans? 

The success of transplanting genes from one mammal to another has opened up the possibilities for life extension in humans. "It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice," Gorbunova says. "Our next goal is to transfer this benefit to humans." 

Researchers are considering two ways of potentially transferring longevity genes from the naked mole rat into the human system. The first is to slow down the process of degrading the HMW-HA compound caused by common influences like oxidative stress. Secondly, these scientists will adopt measures that stimulate the production of these genes to promote increased lifespan in humans. 

"We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials," Andrei Seluanov, a professor of biology says. "We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health." 

Conclusion 

We’re only beginning to scratch the surface of life extension in human and animal life. 

From this study alone, researchers have discovered a means of not only improving longevity, but ways to improve wellbeing, and control the usual decline associated with aging. 

These new findings open up the possibilities for improved human well-being and a better understanding of the inner workings and capabilities of living organisms. 

References:

Hadi F, Kulaberoglu Y, Lazarus KA, et al. Transformation of naked mole-rat cells. Nature. 2020;583(7814):E1-E7. doi:10.1038/s41586-020-2410-x 

Saldmann F, Viltard M, Leroy C, Friedlander G. The Naked Mole Rat: A Unique Example of Positive Oxidative Stress. Oxid Med Cell Longev. 2019;2019:4502819. Published 2019 Feb 7. doi:10.1155/2019/4502819 

Snetkov P, Zakharova K, Morozkina S, Olekhnovich R, Uspenskaya M. Hyaluronic Acid: The Influence of Molecular Weight on Structural, Physical, Physico-Chemical, and Degradable Properties of Biopolymer. Polymers (Basel). 2020;12(8):1800. Published 2020 Aug 11. doi:10.3390/polym12081800 

Gorbunova V, Takasugi M, Seluanov A. Hyaluronan goes to great length. Cell Stress. 2020;4(9):227-229. Published 2020 Jul 17. doi:10.15698/cst2020.09.231