Fibroblasts from naked mole-rats are resistant to multiple forms of cell injury, but sensitive to peroxide, ultraviolet light, and endoplasmic reticulum stress.
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 H(2)O(2), 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.
Salmon
Adam B
AB
Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA.
Sadighi Akha
Amir A
AA
Buffenstein
Rochelle
R
Miller
Richard A
RA
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D005947:Glucose / Q000494:pharmacology; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D019577:Mole Rats; D010269:Paraquat / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D013045:Species Specificity; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D014466:Ultraviolet Rays
D016895:Culture Media, Serum-Free; D002104:Cadmium; D012402:Rotenone; D014415:Tunicamycin; D019284:Thapsigargin; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide; D005947:Glucose; D010269:Paraquat