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)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG006168-27
Application #
8660255
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Guo, Max
Project Start
Project End
Budget Start
Budget End
Support Year
27
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Jiang, James C; Stumpferl, Stefan W; Tiwari, Anurag et al. (2016) Identification of the Target of the Retrograde Response that Mediates Replicative Lifespan Extension in Saccharomyces cerevisiae. Genetics 204:659-673
Jazwinski, S M (2015) Mitochondria to nucleus signaling and the role of ceramide in its integration into the suite of cell quality control processes during aging. Ageing Res Rev 23:67-74
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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
Ayyadevara, Srinivas; Tazearslan, Cagdas; Alla, Ramani et al. (2014) Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae. Front Genet 5:211
Case, Mary E; Griffith, James; Dong, Wubei et al. (2014) The aging biological clock in Neurospora crassa. Ecol Evol 4:3494-507
Jazwinski, S Michal (2014) The retrograde response: a conserved compensatory reaction to damage from within and from without. Prog Mol Biol Transl Sci 127:133-54

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