, 10:443

Age-associated impairment of Akt phosphorylation in primary rat hepatocytes is remediated by alpha-lipoic acid through PI3 kinase, PTEN, and PP2A

Research Article

DOI: 10.1007/s10522-008-9187-x

Cite this article as:
Petersen Shay, K. & Hagen, T.M. Biogerontology (2009) 10: 443. doi:10.1007/s10522-008-9187-x


Akt is a highly regulated serine/threonine kinase involved in stress response and cell survival. Stress response pathways must cope with increasing chronic stress susceptibility with age. We found an age-related lesion in Akt activity via loss of phosphorylation on Ser473. In hepatocytes from old rats, basal phospho-Ser473 Akt is 30% lower when compared to young, but basal phospho-Thr308 Akt is unchanged. (R)-α-lipoic acid (LA), a dithiol compound with antioxidant properties, is effective against age-related increases in oxidative stress and has been used to improve glucose utilization through insulin receptor (IR) pathway-mediated Akt phosphorylation. Treatment with physiologically relevant doses of LA (50 μM) provided a 30% increase in phospho-Ser473. Furthermore, two phosphatases that antagonize Akt, PTEN and PP2A, were both partially inhibited by LA. Thus, LA may be a nutritive agent that can remediate loss of function in the Akt pathway and aid in the survival of liver cells.


PKB/AktPI3 kinaseAgingAlpha-lipoic acidPhosphataseOxidative stress

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Linus Pauling InstituteOregon State UniversityCorvallisUSA
  2. 2.Department of Biochemistry and BiophysicsOregon State UniversityCorvallisUSA