Mitochondria have long been implicated in aging. Most research linking this organelle to aging has stressed the deleterious effects of ROS generated by mitochondria during the course of aging, often hinting at the self-accelerating aspects of this phenomenon. However, it has become clear over the past decade that compensatory cell responses can attenuate the consequences of mitochondrial dysfunction occurring during aging. One of these adaptive responses is the retrograde response, which we demonstrated in yeast allows the cell to live as long as it does (14). This mechanism is now known to operate at the organism level in C. elegans as well (6-7), and evidence for its operation in human cells has been presented (8-10, 21). More recent work has pointed to mitochondrial quality control as an important device mitigating the accumulation of damage to mitochondria, either through intrinsic mechanisms (19-20, 22) or through mitophagy (23). The significance of this quality control for maintenance of age asymmetry between mother and daughter yeast cells is clear (19-20, 24), and it has implications for stem cell aging. The convergence of the retrograde response and mitochondrial quality control and evidence that sphingolipid signaling is involved are exciting new developments (25-26) (Fig. 14).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG006168-26
Application #
8441492
Study Section
Special Emphasis Panel (NSS)
Program Officer
Guo, Max
Project Start
1986-05-01
Project End
2017-03-31
Budget Start
2013-05-15
Budget End
2014-03-31
Support Year
26
Fiscal Year
2013
Total Cost
$304,898
Indirect Cost
$102,308
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Atilano, Shari R; Malik, Deepika; Chwa, Marilyn et al. (2015) Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes. Hum Mol Genet 24:4491-503
Kenney, M Cristina; Chwa, Marilyn; Atilano, Shari R et al. (2014) Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactions. Hum Mol Genet 23:3537-51

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