Many nutritional interventions that increase lifespan are also proposed to postpone age-related declines in motor and cognitive function. Potential sources of anti-aging compounds are the plants and fungi that have adapted to extreme environments. We studied the effects of four commonly consumed and culturally relevant Interior Alaska berry and fungus species (bog blueberry, lowbush cranberry, crowberry, and chaga) on the decline in overall health and neuron function and changes in touch receptor neuron morphology associated with aging. We observed increased wild-type Caenorhabditis elegans lifespan and improved markers of healthspan upon treatment with Alaskan blueberry, lowbush cranberry, and chaga extracts. Interestingly, although all three treatments increased lifespan, they differentially affected the development of aberrant morphologies in touch receptor neurons. Blueberry treatments decreased anterior mechanosensory neuron (ALM) aberrations (i.e., extended outgrowths and abnormal cell bodies) while lowbush cranberry treatment increased posterior mechanosensory neuron (PLM) aberrations, namely process branching. Chaga treatment both decreased ALM aberrations (i.e., extended outgrowths) and increased PLM aberrations (i.e., process branching and loops). These results support the large body of knowledge positing that there are multiple cellular strategies and mechanisms for promoting health with age. Importantly, these results also demonstrate that although an accumulation of abnormal neuron morphologies is associated with aging and decreased health, not all of these morphologies are detrimental to neuronal and organismal health.
Acute myeloid leukemia (AML) is a group of hematological malignancies defined by expanded clonal populations of immature progenitors (blasts) of myeloid phenotype in blood and bone marrow. Given a typical poor prognostic outlook, there is great need for novel agents with anti-AML activity. Devil’s club (Oplopanax horridus) is one of the most significant medicinal plants used among the indigenous people of Southeast Alaska and the coastal Pacific Northwest, with different linguistic groups utilizing various parts of the plant to treat many different conditions including cancer. Studies identifying medically relevant components in Devil’s club are limited. For this research study, samples were extracted in 70% ethanol before in vitro analysis, to assess effects on AML cell line viability as well as to study regulation of tyrosine phosphorylation and cysteine oxidation. The root extract displayed better in vitro anti-AML efficacy in addition to a noted anti-tyrosine kinase activity independent of an antioxidant effect. In vivo therapeutic studies using an immunocompetent murine model of AML further demonstrated that Devil’s club root extract improved the murine survival while decreasing immunosuppressive regulatory T cells and improving CD8+ T-cell functionality. This study defines for the first time an anti-AML efficacy for extracts of Devil’s club.
Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS.
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that is one of the more common pediatric malignancies in addition to occurring with high incidence in the aging population. Unfortunately, these patient groups are quite sensitive to toxicity from chemotherapy. Northern Labrador tea, or Rhododendron tomentosum Harmaja (a.k.a. Ledum palustre subsp. decumbens) or "tundra tea," is a noteworthy medicinal plant used by indigenous peoples in Alaska, Canada, and Greenland to treat a diversity of ailments. However, laboratory investigations of Northern Labrador tea, and other Labrador tea family members, as botanical sources for anticancer compounds have been limited. Utilizing an AML cell line in both in vitro and in vivo studies, as well as in vitro studies using primary human AML patient samples, this study demonstrated for the first time that Northern Labrador tea extracts can exert anti-AML activity and that this may be attributed to ursolic acid as a constituent component. Therefore, this medicinal herb holds the potential to serve as a source for further drug discovery efforts to isolate novel anti-AML compounds.
Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments. DAF-16 is not observed in nuceli nor required for lifespan extension in lifespan-extending Alaskan blueberry treatments and, while DAF-16 is not visibly induced into the nucleus in lifespan-extending Alaskan chaga treatments, it is required for chaga-induced lifespan extension. These findings underscore the importance of DAF-16 in the aging of whole organisms and touch receptor neurons and also, importantly, indicate that this critical pathway is not always activated upon consumption of functional foods that impact aging.
Naphthalene‐2,3‐dicarbaldehyde (NDA), a reagent used for the fluorescent detection of amino acids in the presence of cyanide, self‐condenses in the presence of cyanide ion and methanol at room temperature to yield a unique crystalline product 2, 15‐hydroxybenzo[g]benzo[6,7]isochromeno[4,3‐c]isochromen‐7(15H)‐one. The product is proposed to result from facile air oxidation of NDA to a methyl ester in combination with benzoin condensation. Product 2 does not to form in the absence of air. The gHMBC spectrum of 2 distinguishes it from a possible alternative isomeric condensation product.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.