Mitochondria as a Key Determinant of Aging

For a long time, mitochondria have been considered as primary targets of the aging process, notably through accumulation of oxidative damage and mitochondrial deoxyribonucleic acid (DNA) mutations that lead to gradual decline of mitochondrial function. Recent investigations in various model organisms have revealed conserved molecular pathways that can impact longevity. Intriguingly, some of these longevity pathways involve proteins with key functions in the mitochondria. Furthermore, a growing number of studies indicate that signals emanated from mitochondria can directly impact the longevity of the whole organism. Thus, the mitochondrion organelle likely plays an active and causal role in longevity determination. This renders mitochondria a key determinant in the complex network of physiological signals that modulates longevity.

Keywords: aging; signal transduction; mitochondria; ROS; dietary restriction

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 Further Reading
 On Mitochondria and Bioenergetics
    book Nicholls DG and Ferguson SJ (2002) Bioenergetics 3. New York: Academic Press. ISBN 0-12-518121-3.
 On the Section Mitochondrial ROS and Aging
    Muller FL, Lustgarten MS, Jang Y, Richardson A and Van Remmen H (2007) Trends in oxidative aging theories. Free Radical Biology and Medicine 43: 477–503.
    Finkel T (2001) Reactive oxygen species and signal transduction. IUBMB Life 52: 3–6.
 On the Section Mitochondrial DNA Mutations and Aging
    Krishnan KJ, Greaves LC, Reeve AK and Turnbull DM (2007) Mitochondrial DNA mutations and aging. Annals of the New York Academy of Sciences 1100: 227–240.
 On the Section Mitochondria in Signal Transduction that Affects Lifespan upon Dietary Restriction
    Bishop NA and Guarente L (2007) Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nature Reviews Genetics 8: 835–844.
    Kelly DP and Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes and Development 18: 357–368.
    Lin SJ and Guarente L (2003) Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Current Opinion in Cell Biology 15(2): 241–246.
    Speakman JR, Talbot DA, Selman C et al. (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3: 87–95.
 On the Section Inhibition of Mitochondrial Function in Signal Transduction that Affects Aging
    Liu Z and Butow RA (2006) Mitochondrial retrograde signaling. Annual Review of Genetics 40: 159–185.
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Walter, Ludivine, and Lee, Siu Sylvia(Mar 2009) Mitochondria as a Key Determinant of Aging. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020881]