The groundbreaking achievement of transferring a gene that generates HMW-HA sets the stage for enhancing human health and longevity.
At the University of Rochester, a pioneering effort led by scientists has resulted in the successful transfer of a longevity gene from naked mole rats to mice. This transfer has notably bolstered the health and extended the lifespan of the mice involved.
Naked mole rats, renowned for their extended lifespans and remarkable resilience against age-related ailments, have captivated the interest of the scientific community for some time. By introducing a specific gene accountable for improved cellular repair and safeguarding into mice, the researchers from Rochester have opened up thrilling avenues to unravel the mysteries of aging and elongate the human lifespan.
“Our study demonstrates the potential that distinct longevity mechanisms observed in long-lived mammalian species hold for enhancing the lifespans of other mammals.”
Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester
Gorbunova, together with Andrei Seluanov, a professor of biology, and their collaborators, detail in a study published in Nature how they effectively transferred a gene responsible for producing high molecular weight hyaluronic acid (HMW-HA) from naked mole rats to mice. This transfer resulted in improved health and an approximate 4.4 percent increase in the median lifespan for the mice.
An exceptional mechanism linked to cancer resistance has been unearthed.
Naked mole rats, rodent creatures similar in size to mice, exhibit remarkable longevity compared to other rodents of similar stature, with a potential lifespan of up to 41 years—almost ten times longer. Notably, as they age, these creatures seldom fall victim to diseases commonly observed in other species, such as neurodegeneration, cardiovascular ailments, arthritis, and cancer. Gorbunova and Seluanov have dedicated decades of research to unraveling the distinctive protective mechanisms employed by naked mole rats against aging and diseases.
In their prior research, the scientists unveiled that HMW-HA stands as one of the mechanisms accountable for the exceptional cancer resistance observed in naked mole rats. These creatures possess around ten times more HMW-HA in their bodies compared to mice and humans. When HMW-HA was eliminated from naked mole rat cells, these cells displayed an increased tendency to develop tumors.
With this knowledge in hand, Gorbunova, Seluanov, and their team aimed to determine whether the beneficial effects of HMW-HA could be replicated in other animals.
The transfer of a gene responsible for generating HMW-HA
A mouse model was genetically altered by the team to produce the version of the hyaluronan synthase 2 gene found in naked mole rats, the gene accountable for creating a protein producing HMW-HA. Although all mammals possess the hyaluronan synthase 2 gene, the naked mole rat variant appears to be augmented to stimulate stronger gene expression.
The researchers observed that mice carrying the naked mole rat version of the gene exhibited heightened defense against both spontaneous tumors and chemically induced skin cancer. These mice also demonstrated enhanced overall health and a prolonged lifespan compared to standard mice. As these mice, possessing the naked mole rat gene version, aged, they displayed reduced inflammation across various body regions—an aging indicator—and sustained a healthier gastrointestinal tract.
Although further investigation is necessary to precisely determine why HMW-HA yields such advantageous effects, the researchers posit that its ability to directly regulate the immune system may underlie its benefits.
Could HMW-HA be a potential elixir of youth for humans?
The discoveries unveil fresh opportunities for investigating how HMW-HA might also be applied to enhance longevity and mitigate diseases associated with inflammation in humans.
“It took us 10 years from discovering HMW-HA in the naked mole rat to demonstrating its health-improving effects in mice. Our subsequent aim is to extend this advantage to humans.”
Gorbunova
They anticipate achieving this goal through two potential avenues: either by decelerating HMW-HA’s breakdown or by amplifying its synthesis.
“We’ve already identified compounds that decelerate hyaluronan degradation and are evaluating them in pre-clinical assessments. Our anticipation is that our discoveries will present an initial, yet not singular, instance of how adaptations for longevity from a species with an extended lifespan can be harnessed to promote human health and longevity.”
Seluanov
Abstract
Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent—the naked mole-rat1,2. To study whether the benefits of HMM-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2). nmrHas2 mice showed an increase in hyaluronan levels in several tissues, and a lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHas2 mice shifted towards that of longer-lived species. The most notable change observed in nmrHas2 mice was attenuated inflammation across multiple tissues. HMM-HA reduced inflammation through several pathways, including a direct immunoregulatory effect on immune cells, protection from oxidative stress and improved gut barrier function during ageing. These beneficial effects were conferred by HMM-HA and were not specific to the nmrHas2 gene. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new paths for using HMM-HA to improve lifespan and healthspan.