Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice

Nature. 2023 Sep;621(7977):196-205. doi: 10.1038/s41586-023-06463-0. Epub 2023 Aug 23.


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.

MeSH terms

  • Animals
  • Geroscience
  • Healthy Aging* / genetics
  • Healthy Aging* / immunology
  • Healthy Aging* / physiology
  • Hyaluronan Synthases* / genetics
  • Hyaluronan Synthases* / metabolism
  • Hyaluronic Acid* / biosynthesis
  • Hyaluronic Acid* / metabolism
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Longevity* / genetics
  • Longevity* / immunology
  • Longevity* / physiology
  • Mice
  • Mice, Transgenic
  • Mole Rats* / genetics
  • Neoplasms / genetics
  • Neoplasms / prevention & control
  • Oxidative Stress
  • Rejuvenation / physiology
  • Transcriptome
  • Transgenes / genetics
  • Transgenes / physiology


  • Hyaluronic Acid
  • Hyaluronan Synthases