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Principal Investigator: Shawn Xu
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $368,862
Funding agency: National Institute on Aging
Chemical cues, such as odors and tastants, are best known to regulate animal behavior. Interestingly, such
chemical cues not just regulate behavior, but also other types of critical physiological processes such as
longevity. While chemosensory regulation of behavior has been extensively characterized, much less effort has
been devoted to investigating how chemical cues regulate longevity. Food is a primary environmental factor
that affects aging. Dietary restriction (DR) represents one of the most effective means to extend lifespan in all
tested organisms. How dietary restriction (DR) promotes longevity has been a subject of intensive research;
however, the underlying mechanisms are far from clear. Previous effort has mostly focused on characterizing
how food nutrients regulate longevity. It should be noted that in addition to nutrients, other components are
also found in food. One notable example is the odors associated with food. However, though the mechanisms
by which nutrient signaling regulates lifespan has been extensively characterized, much less is known about
the role of food odors in longevity. As such, it remains largely unclear whether, to what extent, and how food
odors regulates longevity. It is also unclear how the chemosensory system is involved. As odors are integral
components of food, addressing this question will help us to achieve a better understanding of how DR
promotes longevity. It will also help us to understand how the chemosensory system regulates longevity. C.
elegans is a nice genetic model for aging research. Thus far, nearly all the major longevity pathways were first
discovered in invertebrate models such as worms, flies and yeast, and subsequently were found to be
evolutionarily conserved in mammals. This, together with a short lifespan (~3 weeks) and facile genetics,
makes C. elegans a highly valuable model for aging research. We found that food odors regulate DR longevity
in C. elegans, and that the chemosensory system plays a key role in mediating the effect of food-derived odors
on DR longevity. Here, we propose to investigate the underlying neural and genetic mechanisms. To do so, we
will use a combination of neuroscience and aging research tools. As longevity mechanisms tend to be
evolutionarily conserved from worms to mammals, the proposed work will provide novel insights into DR-
dependent longevity in other organisms.
Terms: <5-HT><5-Hydroxytryptamine><5HT><AD dementia><Address><Affect><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Animal Behavior><Behavior><C elegans><C. elegans><C.elegans><CD2 Antigens><CD2 molecule><CD2R><Caenorhabditis elegans><Cell Communication and Signaling><Cell Signaling><Chemicals><Communication><Cues><Data><Degenerative Neurologic Disorders><Dopamine><E-Rosette Receptor><Enteramine><Environmental Factor><Environmental Risk Factor><Esthesia><Flies><Food><G-Proteins><GTP-Binding Proteins><GTP-Regulatory Proteins><GeneHomolog><Genetic><Genetic Models><Guanine Nucleotide Coupling Protein><Guanine Nucleotide Regulatory Proteins><Hippophaine><Homolog><Homologous Gene><Homologue><Hydroxytyramine><Increase lifespan><Intestinal><Intestines><Intracellular Communication and Signaling><Invertebrata><Invertebrates><Length of Life><Levarterenol><Levonorepinephrine><Longevity><Longevity Pathway><Mammalia><Mammals><Mediating><Modeling><Nerve Cells><Nerve Impulse Transmission><Nerve Transmission><Nerve Unit><Nervous System Degenerative Diseases><Neural Cell><Neural Degenerative Diseases><Neural degenerative Disorders><Neurocyte><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neuronal Transmission><Neurons><Neurosciences><Noradrenaline><Norepinephrine><Norsympatol><Norsynephrine><Nutrient><Octopamine><Odors><Organism><Organism-Level Process><Organismal Process><Pathway interactions><Perception><Physiologic Processes><Physiological Processes><Play><Primary Senile Degenerative Dementia><Process><Protocol><Protocols documentation><Regulation><Research><Risk Reduction><Role><SER receptor><Sensation><Sensory><Serotonin><Signal Transduction><Signal Transduction Systems><Signaling><Signaling Factor Proto-Oncogene><Signaling Pathway Gene><Signaling Protein><System><Testing><Transmission><Work><Yeasts><age associated disease><age associated disorder><age associated impairment><age associated neurodegeneration><age associated neurodegenerative disease><age associated neurodegenerative disorder><age dependent disease><age dependent disorder><age dependent impairment><age dependent neurodegeneration><age dependent neurodegenerative condition><age dependent neurodegenerative disease><age dependent neurodegenerative disorder><age related human disease><age related neurodegeneration><age-driven neurodegenerative disorders><age-related disease><age-related disorder><age-related impairment><age-related neurodegenerative disease><age-related neurodegenerative disorder><aging associated neurodegeneration><aging associated neurodegenerative disease><aging related neurodegeneration><aging related neurodegenerative disease><aging related neurodegenerative disorder><axon signaling><axon-glial signaling><axonal signaling><biological signal transduction><bowel><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><detection platform><detection system><diet restriction><dietary restriction><elongating the lifespan><environmental risk><extend life span><extend lifespan><fly><glia signaling><glial signaling><health-span><healthspan><healthy life span><improved><insight><life span><lifespan><lifespan extension><living system><monoamine><nerve signaling><neural><neural signaling><neurodegenerative illness><neuronal><neuronal signaling><neurotransmission><norsynephrine receptor><novel><octopamine receptor><pathway><primary degenerative dementia><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><restricted diet><risk-reducing><senile dementia of the Alzheimer type><sensor><sensory system><social role><tool><transmission process>