On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging.
Hope DangRaul Castro-PortuguezLuis EspejoGrant BackerSamuel S FreitasErica SpenceJeremy MeyersKarissa ShuckEmily A GardeaLeah M ChangJonah BalsaNiall ThornsCaroline CorbanTeresa LiuShannon BeanSusan SheehanRon KorstanjeGeorge L SutphinPublished in: Nature communications (2023)
Tryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes-tdo-2, kynu-1, and acsd-1-for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3HAA. 3HAA increases oxidative stress resistance and activates the Nrf2/SKN-1 oxidative stress response. In pilot studies, female Haao knockout mice or aging wild type male mice fed 3HAA supplemented diet were also long-lived. HAAO and 3HAA represent potential therapeutic targets for aging and age-associated disease.
Keyphrases
- oxidative stress
- wild type
- healthcare
- public health
- poor prognosis
- mental health
- cardiovascular disease
- dna damage
- transcription factor
- papillary thyroid
- ischemia reperfusion injury
- randomized controlled trial
- diabetic rats
- squamous cell carcinoma
- dna methylation
- copy number
- health information
- human health
- squamous cell
- childhood cancer
- long non coding rna
- health promotion