Successful Aging and Sustained Good Health in the Naked Mole Rat: A Long-Lived Mammalian Model for Biogerontology and Biomedical Research
Successful Aging and Sustained Good Health in the Naked Mole Rat: A Long-Lived Mammalian Model for Biogerontology and Biomedical Research
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DOI：
10.1093/ilar.52.1.41
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发表时间：
2011-01-01
期刊：
影响因子：
2.5
通讯作者：
Buffenstein, Rochelle
中科院分区：
文献类型：
--
作者：
Edrey, Yael H.;Hanes, Martha;Buffenstein, Rochelle
裸鼹鼠（NMR; Heterocephalus glaber）是已知寿命最长的啮齿类动物，最长寿命为30年，比根据体型预期的寿命长5倍。这些高度社会化的老鼠大小的啮齿动物自然存在于非洲之角干旱和半干旱地区的地下洞穴中，通常用于行为、神经和生态生理学研究。非常老的NMR（>28岁），像人类一样，显示出与年龄相关的病理学迹象（例如，例如，在一个实施例中，肌肉损失）以及脂褐素色素的积累，但没有肿瘤发生的迹象。事实上，至少80%的NMR维持正常的活动，身体组成，生殖和生理功能，没有明显的年龄相关的发病率或死亡率增加。他们的长寿归功于持续的健康和明显的抗癌能力。很明显，这个物种的生理和生化过程已经进化到极大地延长了它们的健康和寿命。我们和其他人已经测试了各种现有的理论，使用这个物种作为一个非常长寿的动物模型，成功废除老化。令人惊讶的是，NMR具有高水平的氧化应激和相对较短的端粒，但它们在受到细胞应激源时具有极强的弹性，并且似乎能够在恶劣条件下维持其基因组和蛋白质的完整性。挑战在于了解这些动物是如何做到这一点的。阐明这些机制将为延长人类寿命和健康寿命提供有用的信息，使裸鼹鼠成为衰老研究和抵抗慢性年龄相关疾病的真正“超级模型”。
Naked mole rats (NMRs; Heterocephalus glaber) are the longest-living rodents known, with a maximum lifespan of 30 years-5 times longer than expected on the basis of body size. These highly social mouse-sized rodents, naturally found in subterranean burrows in the arid and semiarid regions of the horn of Africa, are commonly used in behavioral, neurological, and ecophysiological research. Very old NMRs (>28 years), like humans, show signs of age-associated pathologies (e. g., muscle loss) as well as the accumulation of lipofuscin pigments, but no signs of tumorigenesis. Indeed, for at least 80% of their lives NMRs maintain normal activity, body composition, and reproductive and physiological functions with no obvious age-related increases in morbidity or mortality rate. Their long lifespan is attributed to sustained good health and pronounced cancer resistance. Clearly physiological and biochemical processes in this species have evolved to dramatically extend both their good health-and lifespan. We and others have tested various current theories using this species as an exceptionally long-lived animal model of successful abrogated aging. Surprisingly, NMRs have high levels of oxidative stress and relatively short telomeres, yet they are extremely resilient when subjected to cellular stressors and appear capable of sustaining both their genomic and protein integrity under hostile conditions. The challenge is to understand how these animals are able to do this. Elucidating these mechanisms will provide useful information for enhancing human life-and health-span, making the naked mole rat a true "supermodel" for aging research and resistance to chronic age-associated diseases.