The naked mole‑rat produces exceptionally high levels of high‑molecular‑mass hyaluronic acid (HMM‑HA), a molecule linked to tissue protection. Researchers transferred the mole‑rat Has2 gene into mice using a CAG promoter and tamoxifen‑controlled activation to mimic postnatal accumulation. The transgenic mice had higher hyaluronan in multiple organs, far fewer cancers, reduced inflammation and oxidative stress, improved gut health and bone density in older females, and ultimately longer healthspans and lifespans.
Naked Mole‑Rat Gene Boosts Hyaluronic Acid and Extends Mice Lifespans — A Step Toward New Anti‑Aging Clues
These Creatures Could Show Us the Key to LongevityEvgeniya Moskova - Getty Images
The humble naked mole‑rat — a wrinkled, subterranean rodent with poor eyesight and a pronounced overbite — hides an extraordinary biological secret: it produces very large amounts of high‑molecular‑mass hyaluronic acid (HMM‑HA). New research shows that transferring the mole‑rat Has2 gene into mice raises tissue hyaluronan levels, lowers cancer incidence and extends both healthspan and lifespan.
What the Study Did
Biologist Vera Gorbunova and colleagues at the University of Rochester engineered mice to express the naked mole‑rat hyaluronic acid synthase 2 gene (nmrHas2 or Has2). To mimic the mole‑rat’s postnatal accumulation of HMM‑HA, the team used a strong CAG promoter to drive expression and delayed early accumulation with tamoxifen‑controlled activation after birth.
Key Findings
Analyses found elevated hyaluronan across multiple organs — including muscle, kidney, intestine, heart and skin — in the Has2 transgenic mice. Crucially, these mice experienced a markedly lower incidence of both spontaneous and experimentally induced cancers compared with controls.
Beyond cancer resistance, Has2 mice showed broader improvements in health and aging markers: many animals remained disease‑free for longer periods, displayed molecular signatures of younger biological age, and ultimately lived longer. Older female mice also exhibited increased bone density, suggesting protection against age‑related bone loss.
Mechanisms and Molecular Effects
Mice expressing the naked mole‑rat Has2 gene had fewer age‑associated changes in their transcriptomes (the RNA expression profiles of tissues). The transgenic animals showed reduced markers of inflammation and oxidative stress, and improved measures of gut health, all of which likely contributed to better healthspan.
“These findings demonstrate that evolutionary adaptations found in long‑lived species such as the naked mole‑rat can be exported and adapted to benefit human health,” Gorbunova and colleagues wrote in their paper published in Nature.
Implications and Limitations
The results suggest that HMM‑HA contributes to cancer resistance and slower biological aging in mammals, and that aspects of this adaptation can be reproduced in another species. However, translating these findings into human therapies will be complex: gene transfer approaches, safety, dosing, tissue specificity, and long‑term effects all require much more study before clinical application.
Overall, the study identifies HMM‑HA as a promising molecular avenue for further research into ageing, inflammation and cancer resistance.
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