Document Detail

Lithocholic acid extends longevity of chronologically aging yeast only if added at certain critical periods of their lifespan.
MedLine Citation:
PMID:  22894934     Owner:  NLM     Status:  MEDLINE    
Our studies revealed that LCA (lithocholic bile acid) extends yeast chronological lifespan if added to growth medium at the time of cell inoculation. We also demonstrated that longevity in chronologically aging yeast is programmed by the level of metabolic capacity and organelle organization that they developed before entering a quiescent state and, thus, that chronological aging in yeast is likely to be the final step of a developmental program progressing through at least one checkpoint prior to entry into quiescence. Here, we investigate how LCA influences longevity and several longevity-defining cellular processes in chronologically aging yeast if added to growth medium at different periods of the lifespan. We found that LCA can extend longevity of yeast under CR (caloric restriction) conditions only if added at either of two lifespan periods. One of them includes logarithmic and diauxic growth phases, whereas the other period exists in early stationary phase. Our findings suggest a mechanism linking the ability of LCA to increase the lifespan of CR yeast only if added at either of the two periods to its differential effects on various longevity-defining processes. In this mechanism, LCA controls these processes at three checkpoints that exist in logarithmic/diauxic, post-diauxic and early stationary phases. We therefore hypothesize that a biomolecular longevity network progresses through a series of checkpoints, at each of which (1) genetic, dietary and pharmacological anti-aging interventions modulate a distinct set of longevity-defining processes comprising the network; and (2) checkpoint-specific master regulators monitor and govern the functional states of these processes.
Michelle T Burstein; Pavlo Kyryakov; Adam Beach; Vincent R Richard; Olivia Koupaki; Alejandra Gomez-Perez; Anna Leonov; Sean Levy; Forough Noohi; Vladimir I Titorenko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-18     Completed Date:  2013-02-06     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3443-62     Citation Subset:  IM    
Department of Biology, Concordia University,Montreal, Quebec, Canada.
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MeSH Terms
Apoptosis / drug effects
Caloric Restriction
Cell Nucleus / drug effects,  genetics
Cells, Cultured
DNA, Fungal / metabolism
DNA, Mitochondrial / metabolism
Fatty Acids, Monounsaturated / pharmacology
Glucose / pharmacology
Lithocholic Acid / pharmacology*
Longevity / drug effects
Mitochondria / drug effects,  genetics,  metabolism
Models, Biological
Osmotic Pressure / drug effects
Saccharomyces cerevisiae / cytology,  drug effects*,  growth & development*
Stress, Physiological / drug effects
Time Factors
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/DNA, Fungal; 0/DNA, Mitochondrial; 0/Fatty Acids, Monounsaturated; 209B6YPZ4I/palmitoleic acid; 434-13-9/Lithocholic Acid; 50-99-7/Glucose

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