Exploring Aging Science: Unique Insights from Naked Mole Rats

The human desire for an extended healthy lifespan drove detailed investigation into the aging process through research on model organisms. The short lifespans and well-documented genetic profiles of Caenorhabditis elegans (a nematode), Drosophila melanogaster (fruit fly), and laboratory mice make them essential model organisms for aging research because they allow precise experimental manipulation. Scientific exploration focuses on the exceptional lifespan of species, including naked mole rats. Scientists study molecular and evolutionary mechanisms of longevity and aging resistance in various species to create potential preventative and therapeutic human health interventions.

Fig. 1 Adult naked mole rats kept in an animal room. (Oka K, et al., 2023)

Naked Mole Rats: The Oldest Rodent Alive

East Africa's native small burrowing rodents, known as naked mole rats, belong to the species Heterocephalus glaber. The journal Science selected naked mole rats as “Vertebrate of the Year” in 2013 because of their widespread scientific interest. Despite having "mole-rat" in their name, these mammals actually share closer genetic ties to porcupines than to standard rodents such as mice or rats.

• The study of aging highlights naked mole rats because they experience long lifespans while resisting common age-related diseases. Naked mole rats exhibit an exceptional lifespan of up to 30 years in captivity, which stands out as unusually lengthy for rodents of their body size.
• Naked mole rats demonstrate exceptional stress resistance and regenerative abilities, which makes them perfect for studying the biological processes related to longevity and healthspan.
• Naked mole rats represent one of the few eusocial mammals that exhibit highly organized social structures comparable to those found in bees and ants. Naked mole rat colonies may contain up to 300 members, with one breeding female who serves as their queen. Reproduction duties fall on the queen while other colony members take care of foraging responsibilities, raising the young, and managing the burrow system. Naked mole rats thrive in difficult habitats because of their collaborative behavior.

Unique Characteristics of Naked Mole Rats

Physical attributes of naked mole rats

Naked mole rats show their distinctiveness through their hairless, wrinkled skin and large incisors used for burrowing. They stand out from other species due to their small size, which measures between 3 to 4 inches in length. Naked mole rats evolved to remain hairless because their underground habitats require efficient temperature control, which helps them survive in hot subterranean conditions.

Unparalleled longevity of naked mole rats

Scientific studies often show that big mammals live longer lives because there exists a general pattern that links maximum lifespan with body mass. However, naked mole rats defy this expectation. These animals survive beyond 37 years, which is five times longer than expected from their size. The unusual lifespan of naked mole rats stands out because they do not adhere to the Gompertz law of mortality, which suggests that death risk grows exponentially with age. Their mortality risk remains unchanged over their entire lifespan, which distinguishes naked mole rats from the majority of mammalian species. The cardiovascular function, body fat content, and bone mineral density of these animals remain unchanged as they get older. The distinctive biological makeup of these animals enables them to oppose standard aging mechanisms while sustaining a healthspan equal to their full lifespan.

Fig. 2 Maximum life-span and longevity quotients for selected rodents. (Buffenstein R and Jarvis JU, 2002)

Marked oxidative stress resistance of naked mole rats

Naked mole rats possess extraordinary physiological adaptations that allow them to survive in conditions with both reduced oxygen levels (hypoxia) and elevated carbon dioxide levels (hypercapnia). These animals can handle extended periods of low oxygen conditions from 3% to 8% for hours up to days and survive a complete lack of oxygen for up to 18 minutes. Their physiological adaptations enable survival in subterranean environments where oxygen availability is severely diminished.

Unlike most mammals that increase their breathing rate during acute low oxygen conditions to boost oxygen intake, naked mole rats follow a unique survival method. The ventilation rate of naked mole rats remains unchanged when oxygen levels decrease, while most mammals increase their breathing rate under similar conditions. They achieve a metabolic rate reduction between 60%-85% and decrease their body temperature by 2-4°C to adapt to low oxygen conditions. The substantial reduction in metabolic activity helps them save energy and reduce oxygen usage, which enables survival in deadly conditions where most mammals cannot live.

Remarkable cancer resistance of naked mole rats

Scientists study how naked mole rats demonstrate extraordinary cancer resistance. These mammals demonstrate exceptional tumor resistance because of their distinctive cellular properties, which differ from many other mammals. The cells of these organisms develop a heightened sensitivity to overcrowding, which activates protective measures that inhibit uncontrolled cell growth.

Unlocking the Aging Mechanism Underlying Naked Mole Rats

Genomic stability and DNA repair

Throughout their extended life spans, naked mole rats maintain genomic stability, which is especially notable in their brain, kidney, and liver tissues. The gene expression patterns of naked mole rats remain unchanged between 4 and 20 years of age, unlike those of mice, rats, and humans. The preservation of genes responsible for essential cellular functions throughout their lifespan leads to both remarkable longevity and disease resistance against aging-related conditions.

High-performance whole-genome sequencing technology advancements have substantially improved our genetic knowledge of naked mole rats. Researchers published the initial complete genome sequence of a male naked mole rat in 2011. Research revealed that expression levels of mitochondrial genes and redox system-related genes showed significant differences. The protection of cells from oxidative stress combined with energy metabolism regulation represents essential biological functions because these processes have major impacts on aging.

Metabolic regulation and antioxidant defense

Naked mole rats decrease their metabolic rate to reduce oxidative stress, which contributes significantly to cellular aging. Reduced levels of reactive oxygen species (ROS) minimize oxidative damage to cellular proteins, lipids, and DNA. These organisms maintain reinforced antioxidant systems, which effectively neutralize ROS to protect cells against oxidative damage. This defense mechanism plays an essential role in preserving cellular health throughout an organism's lifespan.

The naked mole rat stands out as an extraordinary species that pushes the boundaries of what we know about aging processes and healthy living. The distinct biological features and their resilience against aging diseases offer researchers extensive valuable insights. Exploring the secrets of these extraordinary creatures may enable us to discover crucial knowledge that improves human health and extends lifespan. As a leading provider of customized naked mole-rat models and aging research services, CD BioSciences helps clients unlock the secrets of aging. For information about our services, you can contact us or submit an online inquiry.

References

1. Petruseva IO, et al. Genome Stability Maintenance in Naked Mole-Rat. Acta Naturae, 2017, 9 (4): 31-41.
2. Oka K, et al. The Naked Mole-Rat as a Model for Healthy Aging. Annu Rev Anim Biosci, 2023, 11: 207-226.
3. Buffenstein R, Jarvis JU. The naked mole rat--a new record for the oldest living rodent. Sci Aging Knowledge Environ, 2002, 21: pe7.