Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well ...Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.展开更多
A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vege...A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan.The Adventist Health Study-2(AHS-2)cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda,California,one of five“Blue Zones”in the world in which a higher proportion of the population enjoys a longer than average lifespan.We performedmiRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns.We identified several differentially expressed miRNAs between vegetarians and non-vegetarians,which are involved in immune response and cytokine signaling,cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases.Overall,our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs,which may be related in a beneficial manner to the healthspan.Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.展开更多
文摘Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.
基金The genomic work carried out at the Loma Linda University Center for Genomics were funded in part by the National Institutes of Health(NIH)(Grant No.S10OD019960)(CW)This project is partially supported by the American Heart Association(AHA)(Grant No.18IPA34170301)(CW)+1 种基金and also partially supported by NIH(Grants No.HL115195-06(HQ)/subcontract(GSU)#SP00013920-02(CW),and HL137962(HQ)/subcontract(GSU)#SP00013696-01(CW))Subject recruitment and blood collection were partially funded by the LLU Grants for Research and School Partnerships(GRASP)2140309(NG&GL).
文摘A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan,but the underlying mechanisms for these observations are largely unknown.Particularly,it is not known whether a longterm vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan.The Adventist Health Study-2(AHS-2)cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda,California,one of five“Blue Zones”in the world in which a higher proportion of the population enjoys a longer than average lifespan.We performedmiRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns.We identified several differentially expressed miRNAs between vegetarians and non-vegetarians,which are involved in immune response and cytokine signaling,cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases.Overall,our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs,which may be related in a beneficial manner to the healthspan.Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.
