1. Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice.
- Author
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Zhang Z, Tian X, Lu JY, Boit K, Ablaeva J, Zakusilo FT, Emmrich S, Firsanov D, Rydkina E, Biashad SA, Lu Q, Tyshkovskiy A, Gladyshev VN, Horvath S, Seluanov A, and Gorbunova V
- Subjects
- Animals, Mice, Inflammation genetics, Inflammation immunology, Inflammation prevention & control, Mice, Transgenic, Transgenes genetics, Transgenes physiology, Transcriptome, Neoplasms genetics, Neoplasms prevention & control, Oxidative Stress, Geroscience, Rejuvenation physiology, Hyaluronic Acid biosynthesis, Hyaluronic Acid metabolism, Mole Rats genetics, Longevity genetics, Longevity immunology, Longevity physiology, Hyaluronan Synthases genetics, Hyaluronan Synthases metabolism, Healthy Aging genetics, Healthy Aging immunology, Healthy Aging physiology
- 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-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., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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