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Many breeding programs have been implemented in developing countries, many of which have been unsuccessful. To better understand the failure of these breeding programs, it is proposed to analyze their adequacy with innovations that are actually adopted by smallholders. The proposed methodology takes account of these innovations, the reasons for their adoption and the objectives of livestock keeping. The N’Dama cattle-breeding program in Senegal was used as a case study. Surveys were carried out among 54 farmers: 27 breeders who participated in this program, 17 of whom recently resigned, and 27 breeders who have never participated. Feeding was the most frequently cited area of innovation, followed by infrastructure. Genetics, animal health and reproduction held the third rank. Milk production appeared as an important objective of breeders, although the context remains one of strong multifunctionality. Principal component analysis highlighted three categories of breeders according to the innovations they adopted: institutional, modernizing, and integrating innovators. The groups of institutional and modernizing innovators dominate, gathering each 41% of the farmers. In the first category, breeders have organized themselves in an association and use N’Dama sires, livestock aiming at an insurance objective. In the second category, artificial insemination with exotic breeds and other technical innovations (cowshed, vaccination, urea treatment of straw) are used to improve production of milk and meat. The third group is termed ‘integrating innovators,’ since their innovations aim at integrating livestock and crop production. Gathering 18% of the sampled breeders, this group presents intermediate features between the two previous groups, using animals as draught power and for manure production. These results indicate that a process of intensification is at play and that the genetic improvement through the selection of N’Dama cattle for production criteria does not meet the breeders’ demand. However, the N’Dama’s adaptive traits justify its use as part of the breeding strategy of farmers, either in pure-breeding or in crossbreeding. The study thus tends to show the interactive link between genetic improvement and other innovations. It suggests that the success of a breeding program depends on its adequate positioning within the set of innovations adopted by breeders and proposes a method to inform breeding programs accordingly.

Abstract Background Little is known about patient profile changes in medical facilities in our country, leading to this study to describe and compare patient profiles in 2010 and 2022. Patients and methods This was a cross-sectional study with new outpatients aged 15 years and more seen in the cardiology department of the UH-GT. Measurements included height, weight and body mass index (BMI). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. Quantitative data are presented as the mean with standard deviation, and categorical one as proportions. Statistical tests were the t test to compare means and chi-test for categorical variables. The level of significance was set to 0.05. Results The sample consisted of 515 new patients (199 in 2010 and 316 in 2022) with 59.1% female in 2010 and 60.1% in 2022 (p = 0.821). We noticed an increase in hypertension (59.1–71.8%, p = 0.003) and a decrease in tobacco smoking (from 13 to 05.4%, p = 0.002) and stroke (from 05.8 to 02.2%, p = 0.033). Height increased significantly from 1.59 m to 1.66 m, p = 0.002. SBP and DBP showed significant decreases in their means from 155.43 to 144.97 mmHg, p =

Introduction : Le lupus érythémateux systémique est une connectivite fréquente chez les femmes en activité génitale. Au cours du lupus érythémateux systémique, la pseudo-obstruction intestinale est l'une des graves complications rares. Ainsi l'objectif de cet article est de présenter un cas clinique d'atteinte urinaire et pseudo-obstruction intestinale révélatrice d'un lupus érythémateux systémique. Observation : Une patiente âgée de 28 ans mariée, de Nationalité Guinéenne admise pour une diarrhée fébrile, asthénie, météorisme, associée à des douleurs articulaire et abdominale nécessitant une consultation et des bilans sans succès.Une échographie abdominale qui objective un épaississement diffus de la paroi colique et des anses grêles ainsi qu'une ascite de moyenne abondance. La coloscopie révèle un aspect inflammatoire spécifique de la muqueuse iléale. Conclusion : La pseudo-obstruction intestinale peut être inaugurale ou concomitante du lupus érythémateux systémique.

This paper investigates the effects of the pandemic containment periods in France on individuals' movements, expenditure and adaptation to the shock, using billions of French bank card transactions measured before and during the COVID-19 pandemic. We measure not only the effect on consumer expenditure, but also on quantities directly related to the containment restrictions, such as consumer mobility, number of retailers visited, and inter-regional purchases. The results show large effects on these measures of consumers' movements, as well as on both online and offline measures of expenditure, particularly in the first containment period. We also find evidence that consumers adjusted rapidly during the first containment period, mitigating the effects of mobility restrictions via an increasing shift toward online purchasing, and that the nature of the adaptation differed for different types of purchase., (© 2022 Elsevier B.V. All rights reserved.)

Thymidine kinase (TK2) deficiency causes mitochondrial DNA depletion syndrome. We aimed to report the clinical, biochemical, genetic, histopathological, and ultrastructural features of a cohort of paediatric patients with TK2 deficiency. Mitochondrial DNA was isolated from muscle biopsies to assess depletions and deletions. The TK2 genes were sequenced using Sanger sequencing from genomic DNA. All muscle biopsies presented ragged red fibres (RRFs), and the prevalence was greater in younger ages, along with an increase in succinate dehydrogenase (SDH) activity and cytochrome c oxidase (COX)-negative fibres. An endomysial inflammatory infiltrate was observed in younger patients and was accompanied by an overexpression of major histocompatibility complex type I (MHC I). The immunofluorescence study for complex I and IV showed a greater number of fibres than those that were visualized by COX staining. In the ultrastructural analysis, we found three major types of mitochondrial alterations, consisting of concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles. The pathological features in the muscle showed substantial differences in the youngest patients when compared with those that had a later onset of the disease. Additional ultrastructural features are described in the muscle biopsy, such as sarcomeric de-structuration in the youngest patients with a more severe phenotype.

Introduction: In 2011, member states of the World Health Organization (WHO) Africa Regional Office (AFRO) resolved to eliminate Measles by 2020. Our study aims to assess The Gambia's progress towards the set AFRO measles elimination target and highlight surveillance and immunisation gaps to better inform future measles prevention strategies., Material and Methods: A retrospective review of measles surveillance data for the period 2011-2019, was extracted from The Gambia case-based measles surveillance database. WHO-UNICEF national coverage estimates were used for estimating national level MCV coverage. Measles post campaign coverage survey coverage estimates were used to estimate national measles campaign coverage., Results: One hundred and twenty-five of the 863 reported suspected cases were laboratory confirmed as measles cases. More than half (53.6%) of the confirmed cases have unknown vaccination status, 24% of cases were vaccinated, 52.8% of cases occurred among males, and 72.8% cases were among urban residents. The incidence of measles cases per million population was lowest (0) in 2011-2012 and highest in 2015 and 2016 (31 and 23 respectively). The indicator for surveillance sensitivity was met in all years except in 2016 and 2019. Children aged 5-9 years (Incidence Rate Ratio-IRR = 0.6) and residents of Central River region (IRR = 0.21) had lower measles risk whilst unvaccinated (Adjusted IRR = 5.95) and those with unknown vaccination status (IRR 2.21) had higher measles risk. Vaccine effectiveness was 89.5%., Conclusion: The Gambia's quest to attain measles elimination status by 2020 has registered significant success but it is unlikely that all target indicators will be met. Vaccination has been very effective in preventing cases. There is variation in measles risk by health region, and it will be important to take it into account when designing prevention and control strategies. The quality of case investigations should be improved to enhance the quality of surveillance for decision making., Competing Interests: The authors have declared that no competing interests exist.

Background: A national mapping survey of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was conducted in The Gambia in May, 2015. The survey aimed at establishing endemicity of schistosomiasis and soil-transmitted helminthiases to inform decisions on program planning and implementation of mass drug administration (MDA)., Methodology/principal Findings: A cross-section of 10,434 eligible school aged children (SAC), aged 7 to 14 years old were enrolled in the survey. The participants were randomly sampled from 209 schools countrywide using N/50, where N = total eligible children per school. Stool, and urine samples were provided by each child and examined for schistosomiasis and soil-transmitted helminthic infections using double Kato-Katz, urine filtration, dipstick techniques and CCA rapid test kits. Data were managed using online LINKS system enabling real-time data availability and access. Epi Info version 3.5.3 and health mapper version 4.3.2 were used to generate outputs of endemicity and distribution. Descriptions of mapped districts for MDA eligibility and frequency were done with reference to WHO PC strategy recommendations. Mapping results indicated that nationally, the prevalence of schistosomiasis (SCH) and soil-transmitted helminthiases (STH) was 4.3% and 2.5% respectively. In terms of distribution STH are more common in Western Region One (WR1) at 4.1% prevalence, then Lower River Region (LRR) 3.6%, and Western Region Two (WR2) 3.0%. In contrast, SCH indicated much higher prevalence in Central River Region (CRR) at a rate of 14.2%. This is within medium prevalence range, and is followed by Upper River Region (URR) at 9.4%, which is within low prevalence range. At the district level, schistosomiasis prevalence seems to be highest in Niani district (22%) in CRR. Banjul island, the capital city, seems to have the highest prevalence of STH (up to 55%), followed by Kombo South with 22% prevalence. Schistosoma haematobium characterised by haematuria, was the most dominant infection of schistosomiasis discovered followed by Schistosoma mansoni which reported in 0.1% of infections. Out of 42 districts mapped 14, or 38%, of them are co-endemic for soil-transmitted helminthiases (ascariasis, trichuriasis, and hook-worm infections) and schistosomiasis (S. haematobium and S. mansoni)., Conclusions: We identified that 24/42(57%) districts mapped in The Gambia are endemic for schistosomiasis expressing the need for preventive chemotherapy. Twenty (47%) of the districts mapped are endemic for STH. However, only two STH endemic districts namely Banjul (55%) and Kombo South (22%) were within rates eligible for mass drug administration., Competing Interests: The authors have declared that no competing interests exist.

Background: The Gambia initiated a control programme for schistosomiasis in 2015. In light of this, recent and comprehensive data on schistosomiasis is required to effectively guide the control programme. This study aimed to evaluate the prevalence and associated risk factors of schistosomiasis among primary school children in The Gambia., Methods: We utilised data from a previous study conducted in 2015 in 4 regions of The Gambia: North Bank Region (NBR), Lower River Region (LRR), Central River Region (CRR) and Upper River Region (URR). In the parent study, ten schools were selected randomly from each region. Urine and stool samples collected from 25 boys and 25 girls (7-14 years) in each school were examined for urinary schistosomiasis (Schistosoma haematobium infection) and intestinal schistosomiasis (Schistosoma mansoni infection) using urine filtration, dipstick and Kato-Katz methods., Principal Findings: Urinary schistosomiasis had an overall prevalence of 10.2% while intestinal schistosomiasis had a prevalence of 0.3% among the sampled school children. Prevalence of urinary schistosomiasis was significantly different among regions (χ 2 = 279.958, df = 3, p < 0.001), with CRR (27.6%) being the most endemic region, followed by URR (12.0%), then LRR (0.6%), and NBR (0.0%). Prevalence of intestinal schistosomiasis was also significantly variable among regions, with 4 of the 5 positive cases detected in CRR and 1 case in URR. Every school sampled in CRR had at least one student infected with S. haematobium, 50% of schools in URR had S. haematobium infection, and just one school in LRR had S. haematobium infection. While S. haematobium infection was significantly higher in boys (χ 2 = 4.440, df = 1, p = 0.035), no significant difference in infection rate was observed among age groups (χ 2 = 0.882, df = 2, p = 0.643). Two of the 5 students infected with S. mansoni were boys and 3 were girls. Four of these 5 students were in the 10-12 years age group and 1 was in the 7-9 years age group. Macrohaematuria and microhaematuria were found to be statistically associated with presence of S. haematobium eggs in urine. Being a male was a risk factor of S. haematobium infection. Bathing, playing and swimming in water bodies were found to pose less risk for S. haematobium infection, indicating that the true water contact behaviour of children was possibly underrepresented., Conclusion: The findings of this study provide invaluable information on the prevalence of schistosomiasis in The Gambia. This was useful for the schistosomiasis control efforts of the country, as it guided mass drug administration campaigns in eligible districts in the study area. More studies on S. mansoni and its intermediate snail hosts are required to establish its true status in The Gambia. As children sometimes tend to provide responses that potentially please the research or their teacher, data collection frameworks and approaches that ensure true responses in studies involving children should be devised and used., Competing Interests: The authors have declared that no competing interests exist.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 10 2.0 , influenza B virus at 10 2.2 , and SARS-CoV-2 at 10 0.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

Background: The poliovirus has been targeted for eradication since 1988. Kenya reported its last case of indigenous Wild Poliovirus (WPV) in 1984 but suffered from an outbreak of circulating Vaccine-derived Poliovirus type 2 (cVDPV2) in 2018. We aimed to describe Kenya's polio surveillance performance 2016-2018 using WHO recommended polio surveillance standards., Methods: Retrospective secondary data analysis was conducted using Kenyan AFP surveillance case-based database from 2016 to 2018. Analyses were carried out using Epi-Info statistical software (version 7) and mapping was done using Quantum Geographic Information System (GIS) (version 3.4.1)., Results: Kenya reported 1706 cases of AFP from 2016 to 2018. None of the cases were confirmed as poliomyelitis. However, 23 (1.35%) were classified as polio compatible. Children under 5 years accounted for 1085 (63.6%) cases, 937 (55.0%) cases were boys, and 1503 (88.1%) cases had received three or more doses of Oral Polio Vaccine (OPV). AFP detection rate substantially increased over the years; however, the prolonged health workers strike in 2017 negatively affected key surveillance activities. The mean Non-Polio (NP-AFP) rate during the study period was 2.87/ 100,000 children under 15 years, and two adequate specimens were collected for 1512 (88.6%) AFP cases. Cumulatively, 31 (66.0%) counties surpassed target for both WHO recommended AFP quality indicators., Conclusions: The performance of Kenya's AFP surveillance system surpassed the minimum WHO recommended targets for both non-polio AFP rate and stool adequacy during the period studied. In order to strengthen the country's polio free status, health worker's awareness on AFP surveillance and active case search should be strengthened in least performing counties to improve case detection. Similar analyses should be done at the sub-county level to uncover underperformance that might have been hidden by county level analysis.

This study aimed to compare digestive and metabolic characteristics in Sahelian (S) and Majorera (M) goat breeds. Six lactating females from each breed, with an average weight 27.0 ± 1.93 and 23.7 ± 1.27 kg, respectively, were used. Cowpea hay, variety 58/74, was offered as sole feed ingredient, at a rate of 2 kg of fresh matter per animal per day. The animals were placed in metabolic cages and a digestibility test was conducted according to an adaptation period of 15 days and a collection period of 7 days. The daily chemical components offered and refused and recovered faeces, urine and milk were measured in order to assess energy and nitrogen utilization. The M and S goats had similar levels of dry matter (DM) intake as well as nutrient digestibility. On a metabolic weight basis, dry matter intake, gross energy intake, metabolizable and energy intake, digestible energy and energy lost as methane production were significantly higher ( p < 0.01) in M than in S goats. Urinary energy excretion was similar ( p = 0.9) between breeds, while faecal energy output was higher in M than in S goats. The milk energy output from the M goats was higher than that the S goats ( p < 0.05). However, metabolizable to net energy conversion efficiency (klm) was not affected by breed ( p = 0.37), while N intake, milk N yield and faecal N losses, relative to metabolic weight, were significantly higher ( p < 0.05) in M than in S goats. Similarly, the percentage of dietary N intake excreted in urine (UNIN) was higher in S than in M breeds. The breed factor had no effect on N retained, N digestibility, urinary N and N use efficiency. In conclusion, the M and S goats were similar in terms of energy and nitrogen use efficiency, despite higher daily milk production and DM consumption in the M goat. This suggests that the M breed is possibly more dependent on a dense nutrition diet than the S breed but requires less maintenance nitrogen.

Background: The isolation of Extended spectrum βlactamase (ESBLs) producing Enterobacteriaceae among food handlers and their implication as sources of food borne outbreaks are a public health concern. This study seeks to investigate the prevalence of faecal carriage of these bacteria among food handlers in the West Coast Region of The Gambia., Method: This study enrolled 600 participants from 60 Lower Basic Schools in West Coast Region of the country. Stool samples collected from the participants were presumptively screened for the ESBLs producing Enterobacteriaceae, using Drigalski agar, supplemented with 2mg/L cefotaxime. The bacterial colonies that grew on each Drigalski agar were tested for ESBL production by the double disk synergy test as recommended by Clinical and Laboratory Standard Institute (CLSI-2015). The confirmatory analysis for ESBL was determined as the zone of inhibition of cefotaxime and/or ceftazidime to ≥5mm from that of cefotaxime /clavulanicacid and/or ceftazidime/clavulanic acid. The presumptive screening of isolates for AmpC phenotypes was done by testing the organism against cefoxitin. The prevalence of the ESBL carriage was presented in percentages. The association of risk factors to the faecal carriage of ESBLs producing Enterobacteriaceae was performed by Pearson Chi-squared and Fishers Exact at (p ≤ 0.05)., Result: The prevalence of faecal carriage ESBL producing Enterobacteriaceae among food handlers was 5.0% (28/565). We found50% (14/28) and3.57% (1/28) ESBL producing bacteria were presumptive AmpC and carbapenemase resistance phenotype. Themost abundant ESBL producing Enterobacteriaceae were Klebsiella spp 32.1% (9/28) and Escherichia spp 28.6% (8/28). The use of antibiotics in the last 3 months was found to be significantly associated (P = 0.012) with the faecal carriage of ESBLs producing Enterobacteriaceae., Conclusion: The prevalence of faecal carriage of ESBLs producing Enterobacteriaceae among food handlers in the Gambia is low. The history to use of the antibiotics in the last three months was found to be significantly associated with this prevalence. Therefore, the institution of a robust antimicrobial surveillance and treatment of patients with such infections are necessary to curb the spread of these multidrug resistant bacteria in the country. Rational prescription and usage of the antibiotics especially cephalosporin should be advocated both in public and private health facilities., Competing Interests: The authors have declared that no competing interests exist.

Background: Our study aims to estimate hypertension (HTN) prevalence and its predictors in rural and urban area., Methods: We conducted a cross-sectional population-based study involving subjects aged 15 to 65 years. Collected data (sociodemographic, blood pressure, weight, height, and blood glucose) were analyzed using SPSS version 20. A logistic regression was conducted to look for factors associated with HTN., Results: Mean was 47 years. High blood pressure (HBP) prevalence was 21.1 and 24.7%, respectively, in rural and urban setting. In rural area age group significantly predicted hypertension with age of 60 years having more-than-4-times risk of hypertension, whereas, in urban area age group, sex and body mass index were predictors with OR: HTN raising from 2.06 [1.24-3.43] for 30-44 years old to 7.25 [4.00-13.13] for 60 years and more using <30 years as reference. Female sex was protective with OR of 0.45 [0.29-0.71] and using normal weight as reference OR for overweight was 1.54 [1.04-2.27] and 2.67 [1.64-4.36] for obesity., Conclusion: Hypertension prevalence is high and associated factors were age group in rural area and age group, female sex, and body mass index in urban area.

Background: Studies in Sub Saharan Africa have shown that the Circulating Cathodic Antigen point-of-care-test (POC-CCA) is more accurate in the detections of S. mansoni than the microscopic Kato-Katz technique but less is known about the accuracy of this rapid test in detecting S. haematobium infections. This study was intended to evaluate the field accuracy of POC-CCA as a rapid test kit for schistosomiasis mapping in The Gambia., Methods: This prospective study was conducted in 4 regions in the country. Ten schools were randomly selected from each region, and a total of 2018 participants whose ages range from 7 to 14 years were enrolled in the study. Stool and urine samples were collected from each participant from May to June 2015, and tested for S. haematobium and S. mansoni infections in field and laboratory settings. The tests conducted included POC-CCA, double Kato-Katz slides, urine filtration and dipstick for hematuria., Results: Of the 1954 participants that had complete data, the mean age of participants was 9.9 years. The prevalence of children infected with S. haematobium, using urine filtration technique was 10.1% (95% CI: 8.87-11.55). Central River Region had the highest level of urinary schistosomiasis with a prevalence of 28.0% (24.13-32.12).The lowest urinary schistosomiasis prevalence of 0.6% (0.12-1.86) was found in Lower River Region and North Bank Region had no cases of schistosomiasis detected. Only 5 participants were infected with S. mansoni. Using urine filtration as reference standard for the detection of S. haematobium, the sensitivity and specificity of POC-CCA was 47.7% and 75.8%. Whilst sensitivity and specificity of POC-CCA for detecting S. mansoni were 60.0% and 71.2% using double Kato-Katz as reference standard., Conclusion: This study showed lower sensitivity of POC-CCA in detecting S. haematobium. Therefore POC-CCA is less useful for rapid diagnosis of urinary schistosomiasis.

McArdle disease (glycogenosis type V), the most common muscle glycogenosis, is a recessive disorder caused by mutations in PYGM, the gene encoding myophosphorylase. Patients with McArdle disease typically experience exercise intolerance manifested as acute crises of early fatigue and contractures, sometimes with rhabdomyolysis and myoblobinuria, triggered by static muscle contractions or dynamic exercises. Currently, there are no therapies to restore myophosphorylase activity in patients. Although two spontaneous animal models for McArdle disease have been identified (cattle and sheep), they have rendered a limited amount of information on the pathophysiology of the disorder; therefore, there have been few opportunities for experimental research in the field. We have developed a knock-in mouse model by replacing the wild-type allele of Pygm with a modified allele carrying the common human mutation, p.R50X, which is the most frequent cause of McArdle disease. Histochemical, biochemical and molecular analyses of the phenotype, as well as exercise tests, were carried out in homozygotes, carriers and wild-type mice. p.R50X/p.R50X mice showed undetectable myophosphorylase protein and activity in skeletal muscle. Histochemical and biochemical analyses revealed massive muscle glycogen accumulation in homozygotes, in contrast to heterozygotes or wild-type mice, which did not show glycogen accumulation in this tissue. Additional characterization confirmed a McArdle disease-like phenotype in p.R50X/p.R50X mice, i.e. they had hyperCKaemia and very poor exercise performance, as assessed in the wire grip and treadmill tests (6% and 5% of the wild-type values, respectively). This model represents a powerful tool for in-depth studies of the pathophysiology of McArdle disease and other neuromuscular disorders, and for exploring new therapeutic approaches for genetic disorders caused by premature stop codon mutations.

McArdle disease is caused by lack of glycogen phosphorylase (GP) activity in skeletal muscle. Patients experience exercise intolerance, presenting as early fatigue and contractures. In this study, we investigated the effects produced by a lack of GP on several genes and proteins of skeletal muscle in McArdle patients. Muscle tissue of 35 patients and 7 healthy controls were used to identify abnormalities in the patients' transcriptomic profile using low-density arrays. Gene expression was analyzed for the influence of variables such as sex and clinical severity. Differences in protein expression were studied by immunoblotting and 2D electrophoresis analysis, and protein complexes were examined by two-dimensional, blue native gel electrophoresis (BN-PAGE). A number of genes including those encoding acetyl-coA carboxylase beta, m-cadherin, calpain III, creatine kinase, glycogen synthase (GS), and sarcoplasmic reticulum calcium ATPase 1 (SERCA1), were found to be downregulated in patients. Specifically, compared to controls, GS and SERCA1 proteins were reduced by 50% and 75% respectively; also, unphosphorylated GS and SERCA1 were highly downregulated. On BN-PAGE analysis, GP was present with GS in two muscle protein complexes. Our findings revealed some issues that could be important in understanding the physiological consequences of McArdle disease: (i) SERCA1 downregulation in patients could result in impaired calcium transport in type II (fast-twitch) muscle fibers, leading to early fatigability during exercise tasks involving type II fibers (which mostly use glycolytic metabolism), i.e. isometric exercise, lifting weights or intense dynamic exercise (stair climbing, bicycling, walking at a very brisk pace), (ii) GP and GS were found together in two protein complexes, which suggests a new regulatory mechanism in the activity of these glycogen enzymes.

The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain function. We report that mitochondrial protein synthesis is unimpaired in mtDNA mutator mice consistent with the observed minor alterations of steady-state levels of mitochondrial transcripts. These findings refute recent claims that circular mtDNA molecules with large deletions are driving the premature aging phenotype. We further show that the stability of several respiratory chain complexes is severely impaired despite normal synthesis of the corresponding mtDNA-encoded subunits. Our findings reveal a mechanism for induction of aging phenotypes by demonstrating a causative role for amino acid substitutions in mtDNA-encoded respiratory chain subunits, which, in turn, leads to decreased stability of the respiratory chain complexes and respiratory chain deficiency.