Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

Kim, Sang-Kyu; Myers, Leann; Ravussin, Éric; Cherry, Katie E.; Jazwinski, S. Michal

doi:10.1007/s10522-016-9643-y

Cited by 17 publications

(13 citation statements)

References 52 publications

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“…Studies have found that genetic polymorphisms in the UCP3 gene were suggested to be associated with hand grip performances in the elderly population's skeletal muscle. This suggested that the uncoupling process was related to muscle metabolism/catabolism in the elderly [72,73]. In addition, there was evidence that UCP2, UCP3, and UCP4 affect the individual's chances of surviving up to a very old age.…”

Section: Discussionmentioning

confidence: 99%

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Jia

Liu

et al. 2020

Genes

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Studies of the gene and miRNA expression profiles associated with the postnatal late growth, development, and aging of skeletal muscle are lacking in sika deer. To understand the molecular mechanisms of the growth and development of sika deer skeletal muscle, we used de novo RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) analyses to determine the differentially expressed (DE) unigenes and miRNAs from skeletal muscle tissues at 1, 3, 5, and 10 years in sika deer. A total of 51,716 unigenes, 171 known miRNAs, and 60 novel miRNAs were identified based on four mRNA and small RNA libraries. A total of 2,044 unigenes and 11 miRNAs were differentially expressed between adolescence and juvenile sika deer, 1,946 unigenes and 4 miRNAs were differentially expressed between adult and adolescent sika deer, and 2,209 unigenes and 1 miRNAs were differentially expressed between aged and adult sika deer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that DE unigenes and miRNA were mainly related to energy and substance metabolism, processes that are closely associate with the growth, development, and aging of skeletal muscle. We also constructed mRNA–mRNA and miRNA–mRNA interaction networks related to the growth, development, and aging of skeletal muscle. The results show that mRNA (Myh1, Myh2, Myh7, ACTN3, etc.) and miRNAs (miR-133a, miR-133c, miR-192, miR-151-3p, etc.) may play important roles in muscle growth and development, and mRNA (WWP1, DEK, UCP3, FUS, etc.) and miRNAs (miR-17-5p, miR-378b, miR-199a-5p, miR-7, etc.) may have key roles in muscle aging. In this study, we determined the dynamic miRNA and unigenes transcriptome in muscle tissue for the first time in sika deer. The age-dependent miRNAs and unigenes identified will offer insights into the molecular mechanism underlying muscle development, growth, and maintenance and will also provide valuable information for sika deer genetic breeding.

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Section: Discussionmentioning

confidence: 99%

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Jia

Liu

et al. 2020

Genes

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“…In females, a different mechanism appears to be involved. Regulatory variants in UCP2 and UCP3 are associated with FI 34 , and this association is not found in males (Kim et al, 2016a). These two genes encode mitochondrial inner membrane proteins that are called uncoupling proteins.…”

Section: Metabolic Dimensions Of Biological Agementioning

confidence: 95%

“…The variation in UCP2 portends a switch in substrate utilized for respiration from glucose to glutamate (Vozza et al, 2014) as FI 34 increases. There is an interaction between RMR and a UCP3 variant in the positive association with FI 34 that indicates an intensification in respiration (Kim et al, 2016a), such that more energy is expended when FI 34 increases. The relevant variant of UCP3 is associated with a higher hazard ratio for mortality, which we will come back to later.…”

Section: Metabolic Dimensions Of Biological Agementioning

confidence: 99%

Examination of the Dimensions of Biological Age

Jazwinski

Kim

2019

Front. Genet.

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The concept of biological age has been used more and more frequently in aging research in attempts to measure the progress of the biological aging process as opposed to the simple passage of time. Several approaches to quantify biological age have been utilized, including the use of biomarkers in the form of serum analytes, epigenetic markers, and deficit or frailty indices. Among these methods, the deficit index possesses a theoretical basis grounded in systems biology by incorporating networks, with their emergent properties, to describe the complex aging system. Application of the deficit index in human aging studies points to the increased energetic demands posed by an aging system that is losing integration. Different aspects of mitochondrial function appear to be responsible in males and females. The gut microbiome loses complexity in tandem with the host, as biological age increases, with likely impact on host metabolism and immunity. Specific DNA methylation changes are associated with biological age. They suggest declining connectivity within the aging network, at the cellular level. The deficit/frailty index may account for at least part of the departure at older ages of the observed mortality in the population from the exponential increase modeled by the Gompertz equation.

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“…The impact of leptin on uncoupled respiration has also been reported animal trial and this affect adaptive thermogenesis [ 25 ]. In addition, genetic polymorphism in uncoupling proteins (UCP2/3) was associated with improvement of mitochondrial function in human [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study

et al. 2017

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Background: Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction between −866G/A UCP2 (uncoupling protein 2) gene polymorphism, dietary intake and leptin in a population based study. Methods: This is a cross sectional study conducted in adults living at urban area of Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density lipoprotein (HDL) cholesterol, leptin and UCP2 gene polymorphism were obtained in 380 men and female adults. Results: UCP2 gene polymorphism was not significantly associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake and physical activity (all p > 0.05). Leptin was lower in overweight subjects with AA + GA genotypes than those with GG genotype counterparts (p = 0.029). In subjects with AA + GA genotypes there was a negative correlation between leptin concentration (r = −0.324; p < 0.0001) and total energy intake and this correlation was not seen in GG genotype (r = −0.111; p = 0.188). Conclusions: In summary, we showed how genetic variation in −866G/A UCP2 affected individual response to leptin production. AA + GA genotype had a better leptin sensitivity shown by its response in dietary intake and body mass index (BMI) and this explained the protective effect of A allele to obesity.

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Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

Cited by 17 publications

References 52 publications

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Altered miRNA and mRNA Expression in Sika Deer Skeletal Muscle with Age

Examination of the Dimensions of Biological Age

The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study

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