Symposium Overview : Chemical Senses and Longevity
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INTERNATIONAL SYMPOSIUM ON OLFACTION AND TASTE Symposium Overview Chemical Senses and Longevity Claire Murphy Department of Psychology, San Diego State University, San Diego, California, USA Cynthia Kenyon discovered more than 10 years ago that a single change in the DAF2 (delay accelerating factor) gene, which codes a recep- tor similar to the human receptors for the hor- mones insulin and IGF-1, doubled the lifespan in Caenorhabditis elegans. 1 Dr. Kenyon discussed her findings that the regulation of lifespan in C. elegans is regulated by gustatory and olfac- tory input, 2 and then presented recent findings on modulation of longevity by thermosensory neurons. She and her colleagues have demon- strated that certain gustatory neurons inhibit longevity, whereas others promote longevity, most likely by influencing insulin/IGF-1 signal- ing. Dr. Kenyon has reported that in C. elegans, olfactory neurons also influence lifespan, and they act in a distinct pathway that involves the reproductive system. In addition, she finds that a putative chemosensory G protein-coupled re- ceptor that is expressed in some of these sen- sory neurons inhibits longevity. Together her findings imply that the lifespan of C. elegans is regulated by environmental cues and that these cues are perceived and integrated in a complex and sophisticated fashion by specific chemosen- sory neurons. Gert Jansen and his colleagues have identi- fied multiple G proteins that extend lifespan, as well as a mutant that reduces lifespan, in C. elegans. His analyses have demonstrated that a Address for correspondence: Claire Murphy, Ph.D., SDSU/UCSD Joint Doctoral Program, 6363 Alvarado Ct., Suite 101, San Diego, CA 92120-4913. Voice: +619 594 4559; fax: +619 594 3773. [email protected] Chair: Linda Buck Organizers: Wen G. Chen and Claire Murphy number of G proteins, including odr-3, gpa- 1, gpa-11, gpc-1, and pcrg-1 play a role in gustatory plasticity, which involves desensitiza- tion of gustatory neurons and sensitization of nociceptive neurons. In his manuscript, he discusses his proposal that the regulation of lifespan depends not only on chemosensory detection but also on the sensitivity of the sen- sory neurons. 3 Anne Brunet and her colleagues have focused on FOXO transcription factors in studying changes in gene expression that ex- tend lifespan. She has demonstrated that in addition to regulation by the protein kinase Akt in response to insulin/growth factor signal- ing, FOXO transcription factors are also regu- lated in response to nutrition deprivation by the AMP-dependent protein kinase (AMPK) path- way. Decreased energy or glucose levels and decreased leptin levels, as well as exercise, acti- vate the energy-sensing AMPK. Based on her findings, she proposes a model for the mecha- nism whereby dietary restriction activates tar- get genes that facilitate resistance to cumulative damage by oxidative stress and thus, life exten- sion. 4 Scott Pletcher has demonstrated the ex- pression of genes involved in resistance to stress and changes in dietary restriction in Drosophila, which suggests modulation of the effects of di- etary restriction on longevity by olfaction. 5 He presented research that established the very in- teresting finding that anosmia can increase the lifespan of Drosophila, and simply smelling food can somewhat reverse lifespan extension by di- etary restriction. His results suggest that small subsets of sensory neurons can have dramatic effects on lifespan. International Symposium on Olfaction and Taste: Ann. N.Y. Acad. Sci. 1170: 680–681 (2009). doi: 10.1111/j.1749-6632.2009.04491.x c 2009 New York Academy of Sciences. 680
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Transcript of Symposium Overview : Chemical Senses and Longevity
INTERNATIONAL SYMPOSIUM ON OLFACTION AND TASTE
Symposium Overview
Chemical Senses and Longevity
Claire Murphy
Department of Psychology, San Diego State University, San Diego, California, USA
Cynthia Kenyon discovered more than 10 yearsago that a single change in the DAF2 (delayaccelerating factor) gene, which codes a recep-tor similar to the human receptors for the hor-mones insulin and IGF-1, doubled the lifespanin Caenorhabditis elegans.1 Dr. Kenyon discussedher findings that the regulation of lifespan inC. elegans is regulated by gustatory and olfac-tory input,2 and then presented recent findingson modulation of longevity by thermosensoryneurons. She and her colleagues have demon-strated that certain gustatory neurons inhibitlongevity, whereas others promote longevity,most likely by influencing insulin/IGF-1 signal-ing. Dr. Kenyon has reported that in C. elegans,olfactory neurons also influence lifespan, andthey act in a distinct pathway that involves thereproductive system. In addition, she finds thata putative chemosensory G protein-coupled re-ceptor that is expressed in some of these sen-sory neurons inhibits longevity. Together herfindings imply that the lifespan of C. elegans isregulated by environmental cues and that thesecues are perceived and integrated in a complexand sophisticated fashion by specific chemosen-sory neurons.
Gert Jansen and his colleagues have identi-fied multiple G proteins that extend lifespan,as well as a mutant that reduces lifespan, in C.
elegans. His analyses have demonstrated that a
Address for correspondence: Claire Murphy, Ph.D., SDSU/UCSDJoint Doctoral Program, 6363 Alvarado Ct., Suite 101, San Diego,CA 92120-4913. Voice: +619 594 4559; fax: +619 594 [email protected]
Chair: Linda BuckOrganizers: Wen G. Chen and Claire Murphy
number of G proteins, including odr-3, gpa-1, gpa-11, gpc-1, and pcrg-1 play a role ingustatory plasticity, which involves desensitiza-tion of gustatory neurons and sensitization ofnociceptive neurons. In his manuscript, hediscusses his proposal that the regulation oflifespan depends not only on chemosensorydetection but also on the sensitivity of the sen-sory neurons.3 Anne Brunet and her colleagueshave focused on FOXO transcription factors instudying changes in gene expression that ex-tend lifespan. She has demonstrated that inaddition to regulation by the protein kinaseAkt in response to insulin/growth factor signal-ing, FOXO transcription factors are also regu-lated in response to nutrition deprivation by theAMP-dependent protein kinase (AMPK) path-way. Decreased energy or glucose levels anddecreased leptin levels, as well as exercise, acti-vate the energy-sensing AMPK. Based on herfindings, she proposes a model for the mecha-nism whereby dietary restriction activates tar-get genes that facilitate resistance to cumulativedamage by oxidative stress and thus, life exten-sion.4 Scott Pletcher has demonstrated the ex-pression of genes involved in resistance to stressand changes in dietary restriction in Drosophila,which suggests modulation of the effects of di-etary restriction on longevity by olfaction.5 Hepresented research that established the very in-teresting finding that anosmia can increase thelifespan of Drosophila, and simply smelling foodcan somewhat reverse lifespan extension by di-etary restriction. His results suggest that smallsubsets of sensory neurons can have dramaticeffects on lifespan.
International Symposium on Olfaction and Taste: Ann. N.Y. Acad. Sci. 1170: 680–681 (2009).doi: 10.1111/j.1749-6632.2009.04491.x c© 2009 New York Academy of Sciences.
680
Murphy: Chemical Senses and Longevity 681
An important aim of aging research is dis-covering drugs that would not only prolonglife but extend vitality. Linda Buck discussedher highly significant recent work using a high-throughput screen for chemicals that delay ag-ing.6 She and her colleagues have identified adrug, used as an antidepressant in humans, thatincreases lifespan in C. elegans, likely through afood-perception pathway responsive to dietaryrestriction.
Thus, this symposium addressed the fol-lowing aims: (1) to bring together scien-tists at the forefront of research on longevityand the chemical senses, (2) to stimulateinvestigation into the mechanisms that un-derlie longevity and the dramatic changesattributable to olfactory and gustatory in-put, (3) to facilitate the application of state-of-the-art innovative technology, particularlygenetic, molecular, and cellular biological tech-niques, to research on longevity and the chem-ical senses, and (4) to identify directions forfuture research in chemosensory science. Tothese ends, the speakers introduced novel ap-proaches and hypotheses that have the potentialto stimulate research into the mechanisms oflongevity and stimulate further chemosensoryresearch that has the potential to identify treat-ments that delay aging and age-related diseases.The significance of this research is potentiallyprofound.
Acknowledgment
Supported by Conference Grant#1U13AG032223 from the National Insti-tute on Aging to C. M. with NIA ProgramSupport.
Conflicts of Interest
The author declares no conflicts of interest.
References
1. Kenyon, C. et al. 1993. A C. elegans mutant that livestwice as long as wild type. Nature 355: 461–464.
2. Alcedo, J. & C. Kenyon. 2004. Regulation of C. eleganslongevity by specific gustatory and olfactory neurons.Neuron 41: 45–55.
3. Hannes, L., M. P. J. Dekkers, R. Hukema, et al. 2009.Signaling proteins that regulate NaCl chemotaxis re-sponses modulate longevity in C. elegans. Ann. N. Y. Acad.
Sci. International Symposium on Olfaction and Taste.1170: 682–687.
4. Greer, E.L., M.R. Banko & A. Brunet. 2009. AMP-activated protein kinase and FoxO transcription factorsin dietary restriction induced longevity. Ann. N. Y. Acad.
Sci. International Symposium on Olfaction and Taste.1170: 688–692.
5. Pletcher, S. 2009. The modulation of lifespan by per-ceptual systems. Ann. N. Y. Acad. Sci. International Sym-posium on Olfaction and Taste. 1170: 693–697.
6. Petrascheck, M., X. Ye & L.B. Buck. 2009. A highthroughput screen for chemicals that increase the lifes-pan of Caenorhabditis elegans. Ann. N. Y. Acad. Sci. Inter-national Symposium on Olfaction and Taste. 1170:698–701.
