High autophagy in the naked mole rat may play a significant role in maintaining good health

Cell Physiol Biochem. 2014;33(2):321-32. doi: 10.1159/000356672. Epub 2014 Feb 5.

Abstract

Background/aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice.

Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA) for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry.

Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old) and adult C57BL/6 mice (eight weeks old) have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases.

Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Hepatic Stellate Cells / metabolism
  • Immunosuppressive Agents / pharmacology
  • Longevity / drug effects
  • Longevity / physiology*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Mole Rats
  • Sirolimus / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • Immunosuppressive Agents
  • Microtubule-Associated Proteins
  • 3-methyladenine
  • Adenine
  • Sirolimus