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Fibroblasts From Naked Mole-Rats Are Resistant to Multiple Forms of Cell Injury, But Sensitive to Peroxide, Ultraviolet Light, and Endoplasmic Reticulum Stress

¹ Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor.
² Department of Pathology and the Geriatrics Center, University of Michigan, Ann Arbor.
³ Department of Biology, City College of New York, New York.
⁴ The Barshop Institute for Aging and Longevity Studies and ⁵ Department of Physiology, University of Texas Health Science Center, San Antonio.
⁶ Ann Arbor VA Medical Center, Michigan.

Address correspondence to Richard A. Miller, MD, PhD, Room 3001 BSRB Box 2200, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200. E-mail: millerr{at}umich.edu

Fibroblasts from long-lived mutant mice are resistant to many forms of lethal injury as well as to the metabolic effects of rotenone and low-glucose medium. Here we evaluated fibroblasts from young adult naked mole-rats (NMR; Heterocephalus glaber), a rodent species in which maximal longevity exceeds 28 years. Compared to mouse cells, NMR cells were resistant to cadmium, methyl methanesulfonate, paraquat, heat, and low-glucose medium, consistent with the idea that cellular resistance to stress may contribute to disease resistance and longevity. Surprisingly, NMR cells were more sensitive than mouse cells to H₂O₂, ultraviolet (UV) light, and rotenone. NMR cells, like cells from Snell dwarf mice, were more sensitive to tunicamycin and thapsigargin, which interfere with the function of the endoplasmic reticulum (ER stress). The sensitivity of both Snell dwarf and NMR cells to ER stress suggests that alterations in the unfolded protein response might modulate cell survival and aging rate.

Key Words: Longevity • Comparative biology • Naked mole-rat • Stress resistance • Oxidation • Endoplasmic reticulum (ER) stress

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