Lithocholic acid extends longevity of chronologically aging yeast only if added at certain critical periods of their lifespan

Abstract

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.

Keywords: :

• aging as a developmental program
• anti-aging compounds
• caloric restriction
• cellular aging
• lithocholic bile acid
• longevity
• longevity control system
• longevity network
• longevity-defining checkpoints
• yeast

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We acknowledge the Centre for Structural and Functional Genomics at Concordia University for outstanding services. This study was supported by grants from the NSERC of Canada and Concordia University Chair Fund. M.T.B. was supported by a Doctoral Research Fellowship Award from the FQRNT. P.K. was supported by Doctoral Research Fellowship Awards from the Fonds de recherché en santé du Quebec and from the Fonds québécois de la recherche sur la nature et les technologies (FQRNT). A.B. and V.R.R. were supported by Frederick Banting and Charles Best Doctoral Scholarship Awards from the Canadian Institutes of Health Research. V.I.T. is a Concordia University Research Chair in Genomics, Cell Biology and Aging.