Journal
AGEING RESEARCH REVIEWS
Volume 8, Issue 3, Pages 173-188Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.arr.2009.03.003
Keywords
Mitochondria; Aging; SIRT1; PGC-1 alpha; Metabolism; AMPK
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Funding
- National Science Foundation
- Brookdale Foundation
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Mitochondria are dynamic organelles that integrate environmental signals to regulate energy production, apoptosis and Ca2+ homeostasis. Not surprisingly, mitochondrial dysfunction is associated with aging and the pathologies observed in age-related diseases. The vast majority of mitochondrial proteins are encoded in the nuclear genome, and so communication between the nucleus and mitochondria is essential for maintenance of appropriate mitochondrial function. Several proteins have emerged as major regulators of mitochondrial gene expression, capable of increasing transcription of mitochondrial genes in response to the physiological demands of the cell. In this review, we will focus on PGC-1 alpha, SIRT1, AMPK and mTOR and discuss how these proteins regulate mitochondrial function and their potential involvement in aging, calorie restriction and age-related disease. We will also discuss the pathways through which mitochondria signal to the nucleus. Although such retrograde signaling is not well studied in mammals, there is growing evidence to suggest that it may be an important area for future aging research. Greater understanding of the mechanisms by which mitochondria and the nucleus communicate will facilitate efforts to slow or reverse the mitochondrial dysfunction that occurs during aging. Published by Elsevier Ireland Ltd.
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