| First Author | Zhang Z | Year | 2023 |
| Journal | Nature | Volume | 621 |
| Issue | 7977 | Pages | 196-205 |
| PubMed ID | 37612507 | Mgi Jnum | J:349215 |
| Mgi Id | MGI:7647050 | Doi | 10.1038/s41586-023-06463-0 |
| Citation | Zhang Z, et al. (2023) Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice. Nature 621(7977):196-205 |
| abstractText | 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-rat(1,2). 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. |
