MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ag...MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles （MVs）, or in complex with other factors such as RNA-binding proteins and high-density lipoprotein （HDL） particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.展开更多
Ageing and cancer have been associated with genetic and genomic changes. The identification of common signatures between ageing and cancer can reveal shared molecular mechanisms underlying them. In this study, we coll...Ageing and cancer have been associated with genetic and genomic changes. The identification of common signatures between ageing and cancer can reveal shared molecular mechanisms underlying them. In this study, we collected ageing-related gene signatures from ten pub- lished studies involved in six different human tissues and an online resource. We found that most of these gene signatures were tissue- specific and a few were related to multiple tissues. We performed a genome-wide examination of the expression of these signatures in various human tumor types, and found that a large proportion of these signatures were universally differentially expressed among normal vs. tumor phenotypes. Functional analyses of the highly-overlapping genes between ageing and cancer using DAVID tools have iden- tified important functional categories and pathways linking ageing with cancer. The convergent and divergent mechanisms between age- ing and cancer are discussed. This study provides insights into the biology of ageing and cancer, suggesting the possibility of potential interventions aimed at postponing ageing and preventing cancer.展开更多
Human beings evolved to run over a relatively short evolutionary time scale, ~1 million years, 2-3 million years ago, markedly increasing metabolic rate and VO2max, compared with other primates, while increasing brain...Human beings evolved to run over a relatively short evolutionary time scale, ~1 million years, 2-3 million years ago, markedly increasing metabolic rate and VO2max, compared with other primates, while increasing brain size,and lifespan. Ageing leads to precise declines in performance and metabolism(VO2max): are there links with ageing-related diseases? Glucocerebrosidase(GCase;GBA1 subtype) mutations are the most common cause of Parkinson Disease,where there is lysosomal disruption and a reciprocal feedback between glucosylceramide and a-synuclein. We have shown that GBA2 is elevated and, using metabolomics, that ceramide and glucosylceramide levels are critically modified presymptomatically and at early stage in the spinal cord of superoxide dismutase1 mutant mice(SOD1G86R, ALS model),and lipid metabolism is massively changed at end stage disease. Modification of glucosylceramide synthase(GCS), and GCase activites shows that inhibiting GCS is deleterious and inhibiting GCase is beneficial to both neuromuscular junction function in sciatic nerve crush, and also grip strength and survival in the SOD1G86R model. Ambroxol(3 mmol·L-1 in drinking water), a glucocerebrosidase chaperone, accelerated recovery of NMJ function in sciatic nerve crush, and ameliorated grip strength and survival in the SOD1G86R model. Ambroxol is phase 2 ready in ALS and starting phase 3 in Parkinson disease.展开更多
基金supported by the grants from the National Institutes of Health(AG17242 and GM 104459)(to Y.S.)a grant from KRIBB Research Initiative Program(to Y.S.)
文摘MicroRNAs （miRNAs） are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They are involved in important biological processes including development, homeostasis, and ageing. Recently, extracellular miRNAs have been discovered in the bloodstream and bodily fluids. These miRNAs are shown to be secreted and circulating in microvesicles （MVs）, or in complex with other factors such as RNA-binding proteins and high-density lipoprotein （HDL） particles. These cell-free, circulating miRNAs can be taken into and function as negative regulators of target genes in recipient cells. Here we review the biogenesis and uptake of circulating miRNAs as well as their profiles in ageing and ageing-related diseases. We discuss the emerging role of circulating miRNAs as biomarkers and therapeutic targets.
文摘Ageing and cancer have been associated with genetic and genomic changes. The identification of common signatures between ageing and cancer can reveal shared molecular mechanisms underlying them. In this study, we collected ageing-related gene signatures from ten pub- lished studies involved in six different human tissues and an online resource. We found that most of these gene signatures were tissue- specific and a few were related to multiple tissues. We performed a genome-wide examination of the expression of these signatures in various human tumor types, and found that a large proportion of these signatures were universally differentially expressed among normal vs. tumor phenotypes. Functional analyses of the highly-overlapping genes between ageing and cancer using DAVID tools have iden- tified important functional categories and pathways linking ageing with cancer. The convergent and divergent mechanisms between age- ing and cancer are discussed. This study provides insights into the biology of ageing and cancer, suggesting the possibility of potential interventions aimed at postponing ageing and preventing cancer.
文摘Human beings evolved to run over a relatively short evolutionary time scale, ~1 million years, 2-3 million years ago, markedly increasing metabolic rate and VO2max, compared with other primates, while increasing brain size,and lifespan. Ageing leads to precise declines in performance and metabolism(VO2max): are there links with ageing-related diseases? Glucocerebrosidase(GCase;GBA1 subtype) mutations are the most common cause of Parkinson Disease,where there is lysosomal disruption and a reciprocal feedback between glucosylceramide and a-synuclein. We have shown that GBA2 is elevated and, using metabolomics, that ceramide and glucosylceramide levels are critically modified presymptomatically and at early stage in the spinal cord of superoxide dismutase1 mutant mice(SOD1G86R, ALS model),and lipid metabolism is massively changed at end stage disease. Modification of glucosylceramide synthase(GCS), and GCase activites shows that inhibiting GCS is deleterious and inhibiting GCase is beneficial to both neuromuscular junction function in sciatic nerve crush, and also grip strength and survival in the SOD1G86R model. Ambroxol(3 mmol·L-1 in drinking water), a glucocerebrosidase chaperone, accelerated recovery of NMJ function in sciatic nerve crush, and ameliorated grip strength and survival in the SOD1G86R model. Ambroxol is phase 2 ready in ALS and starting phase 3 in Parkinson disease.
