Journal of Bioenergetics and Biomembranes

, Volume 46, Issue 4, pp 329–335 | Cite as

Complex-I-ty in aging

  • Jae H. Hur
  • Devon A. Stork
  • David W. Walker


The role of mitochondrial complex I in aging has been studied in both C. elegans and Drosophila, where RNAi knock down of specific complex I subunits has been shown to extend lifespan. More recently, studies in Drosophila have shown that an increase in mitochondrial activity, including complex I-like activity, can also slow aging. In this review, we discuss this apparent paradox. Improved maintenance of mitochondrial activity, mitochondrial homeostasis, may be responsible for lifespan extension in both cases. Decreased electron transport chain activity caused by reducing complex I subunit expression prompts an increase in stress response signaling that leads to enhanced mitochondrial homeostasis during aging. Increased complex I activity, as well as mitochondrial biogenesis, is expected to both directly counteract the decline in mitochondrial health that occurs during aging and may also increase cellular NAD+ levels, which have been linked to mitochondrial homeostatic mechanisms through activation of sirtuins. We suggest that manipulations that increase or decrease complex I activity both converge on improved mitochondrial homeostasis during aging, resulting in prolonged lifespan.


Electron transport chain Sirtuin Mitochondrial homeostasis Hormesis 



We apologize to our colleagues whose work we could not cite due to space limitations. DWW is supported by the National Institute on Aging (R01 AG037514, R01 AG040288).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of BiologyHarvey Mudd CollegeClaremontUSA
  2. 2.Department of Physiological ScienceUniversity of California, Los AngelesLos AngelesUSA
  3. 3.Molecular Biology InstituteUniversity of California, Los AngelesLos AngelesUSA

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