What governs how fast we age? Why do some biological processes stop working earlier than others? And what is happening at the molecular and cellular level as some organisms age while others continue to thrive?
Although seemingly philosophical in nature, these questions address one of the major mysteries of biology, the process of aging. With recent developments in genetics, molecular biology, and genomics, we now have the possibility of addressing these questions at the molecular level. Because our ultimate goal is not simply to extend lifespan, but to improve overall health, we must identify the genes associated with biological functions that we typically associate with quality of life. The goal of our laboratory's work is to understand the molecular mechanisms governing longevity and maintenance of the biological processes that exhibit age-related decline.
Cross-kingdom recognition of bacterial small RNAs induces transgenerational pathogenic avoidance
Gut feelings: microRNAs tune protein quality control and ageing to odoursJournal Article
A new study in C. elegans identifies a microRNA-dependent mechanism that enables olfactory neurons to rapidly regulate protein degradation in the intestine and therefore organismal ageing.2522-5812
Insulin-like peptides and the mTOR-TFEB pathway protect \textitCaenorhabditis elegans hermaphrodites from mating-induced deathInsulin-like peptides and the mTOR-TFEB pathway protect \textitCaenorhabditis elegans hermaphrodites from mating-induced deathJournal Article
Lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear...insulin signaling; lifespan; mating; mTOR; TFEB
Investigating Mechanisms that Control Ubiquitin-Mediated DAF-16/FOXO Protein Turnover.Journal Article
Protein turnover of FOXO family transcription factors is regulated by the ubiquitin-proteasome system. A complex interplay of factors that covalently attach certain types of ubiquitin chains (E3-ubiquitin ligases), and enzymes that are able to remove ubiquitin conjugates (deubiquitylases), regulate the degradation of FOXO proteins by the...
The nematode Caenorhabditis elegans as a model for aging research
A PBX/MEIS Complex Balances Reproduction and Somatic ResilienceJournal Article
Piwi/PRG-1 Argonaute and TGF-β Mediate Transgenerational Learned Pathogenic AvoidanceJournal Article
The ability to inherit learned information from parents could be evolutionarily beneficial, enabling progeny to better survive dangerous conditions. We discovered that, after C. elegans have learned to avoid the pathogenic bacteria Pseudomonas aeruginosa (PA14), they pass this learned behavior on to their progeny, through either the male or...0092-8674
Profiling of presynaptic mRNAs reveals a role for axonal PUMILIOs in associative memory formationJournal Article
Presynaptic protein synthesis is important in the adult central nervous system; however, the set of mRNAs localized to presynaptic areas has yet to be identified in any organism. We differentially labeled somatic and synaptic compartments nervous system-wide in adult C. elegans and isolated synaptic regions for deep sequencing. Analysis of the...
ZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regenerationZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regenerationJournal Article
Aging is associated with reduced capacity for tissue repair, perhaps the most critical of which is a decline in the ability of aged neurons to recover after injury. Identifying factors that improve the regenerative ability of aging neurons is a prerequisite for therapy design and remains an enormous challenge, yet many of the genes that play a...
Activation of G Signaling Enhances Memory Consolidation and Slows Cognitive Decline.Journal Article
Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-...