RSS 1.0Faculty of Medicine, Dentistry and Life Sciences
The Faculty of Life Sciences is predominantly based on the Chester Campus, with sports-related and computer-related courses also delivered at Warrington. A number of specialist courses are also delivered at our partner associate college at Reaseheath in Cheshire, as well as some delivery outside the UK. The Faculty also supports several research centres.
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Screening for Mental Illness using GMHAT App of patients with Type 2 Diabetes Mellitus at a tertiary care hospital in India – A cross sectional studyPeople with diabetes will have some coexisting mental illness most of the time and its evaluation and management are essential for the well‑being of the person. With this background, the Global Mental Health Assessment Tool (GMHAT) app was used to screen for mental illness among type 2 diabetes mellitus patients in Mysore, India. Methods: A cross‑sectional study was conducted on 100 patients who were on treatment for type 2 diabetes for at least 6 months. Interviews were conducted using a structured GMHAT. Results: The mean age of the study participants was 48.8 ± 11.6 years. Among the 100 diabetic patients, 39% (n = 39) had mental illness and among the 39 subjects, 21% had depression, 14% had anxiety disorder and 4% suffered from organic disorder. Apart from diabetes, 29, 17, 13, 27, 23 and 20% had hypertension, chronic kidney disease, liver disease, retinopathy, neuropathy and nephropathy, respectively, as comorbid conditions. Conclusion: There is a higher prevalence of mental illness in patients with diabetes mellitus. The prevalence rate increases with an increase in the chronicity of diabetes. The use of the GMHAT app will help in rapid assessment and accurate diagnoses
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“It’s Like Being Pushed into Sea on a Boat with No Oars”: Breast cancer survivorship and rehabilitation support in Ireland and the United KingdomBackground: Cancer survivorship is associated with co-morbidities including anxiety, depression, and cardiovascular disease. Rehabilitative care post treatment is vital for survivors’ psychological and physical well-being. The aims of this study were to investigate breast cancer survivors’ attitudes towards their health post-treatment; their awareness of co-morbidities associated with treatment; and their awareness of support systems available. Methodology: A qualitative research approach was employed, using semi-structured interviews with breast cancer survivors from the UK and Ireland. Data were analysed using thematic analysis. Eight breast cancer survivors were recruited through purposive sampling. Results: Two themes emerged from the data 1) Health & Rehabilitation Post Treatment, which included mental and physical health and a desire to control one’s own health in survivorship as well as a discussion around co-morbidities, and 2) Access to support services in survivorship which highlighted both positive and negative experiences of accessing support, as well as reasons for not accessing support in survivorship. Principal Conclusions: Access to rehabilitation support including diet, exercise and stress management are key components in survivorship. Rehabilitation and support services need to be more readily available for survivors to aid them in this journey and to educate them on the increased risk of conditions such as CVD with cancer treatment. Utilising current cardiac rehabilitation models could be a solution to provide a holistic cancer rehabilitation thus providing the lifelong support cancer survivors both want and need.
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The effects of allogrooming and social network position on behavioural indicators of stress in female lion-tailed macaques (Macaca silenus)Allogrooming serves an important social function in primates and confers short term benefits such as parasite removal and stress-relief. There is currently mixed evidence as to the immediate impact of allogrooming on an individual’s stress levels, which may be influenced by their role in the grooming dyad, position in their social network, or their relationship with their grooming partner. In this study of seven captive adult female lion-tailed macaques (Macaca silenus) in a mixed sex group at Chester Zoo, UK, we found evidence to support a tension-reduction function of allogrooming. Focal animal sampling showed that the duration of self-directed behaviour (SDB), which indicates moderate to high levels of stress, was significantly lower in the five-minute period following allogrooming than the five-minute minute period preceding it for both recipients and groomers. However, when compared to match-control periods, both SDB rates and durations were significantly lower across all individuals in the five-minute period both before and after allogrooming, indicating that although allogrooming reduces stress, it is also more likely to occur when individuals are already in a relatively relaxed state. The rate and duration of SDB post-grooming did not correlate with the strength of a dyad’s bond (based on proximity). This suggests that it is the act of allogrooming itself, rather than the identity of the partner, that reduces stress for both parties. Analysis of the proximity network highlighted a clear cost to social integration; node strength, a measure of the number and strength of an individual’s direct relationships, positively correlated with the duration of self-directed behaviour, suggesting that more gregarious individuals may experience higher levels of stress. These findings add to the growing body of literature that examines the effect of the individual social environment on primate stress levels, and also highlight the need to further investigate the link between social integration and the stress experienced by group-living animals.
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N-3 fatty acid supplementation mediates lipid profile, including small dense LDL, when combined with statins: a randomized double blind placebo controlled trialBackground: Epidemiological and clinical evidence suggests that high-dose intake of omega 3 fatty acids (n-3 FA) have a favorable role in altering serum triglycerides (TG) and non-high density lipoprotein cholesterol (non-HDL-C) when combined with statins in hyperlipidemic patients. Their efficacy in altering low-density lipoprotein cholesterol (LDL-C) particle size is yet to be established. Aim: This study evaluated the effects of supplementing 4 g/day Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on serum blood lipids, including small, dense LDL-C particle concentration, in hyperlipidemic patients receiving stable statin therapy. Methods: In this randomized, placebo-controlled, double-blind parallel group study, 44 patients on statin therapy for > 8 weeks with non-HDL-C concentrations above 130 mg/dL were randomized into two groups. For 8 weeks, together with their prescribed statin, the intervention group received 4 g/day EPA + DHA (3000 mg EPA + 1000 mg DHA in ethyl ester form) and the placebo group received 4 g/day olive oil (OO). Measurements of serum non-HDL-C, TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C (including large - LDL I; intermediate - LDL II; and small - LDL III subclasses), very-low-density lipoprotein cholesterol (VLDL-C) concentration, were taken at baseline and post-intervention. Dietary intake was assessed with a weighed intake, 3-day food diary at week 4. Primary outcome measures were percent change in LDL III, non-HDL-C and LDL particle number. Results: At the end of treatment, the median percent change in serum LDL III concentration was significantly greater in the n-3 FA group plus atorvastatin compared to placebo (− 67.5% vs − 0%, respectively; P < 0.001). Supplemen- tation with n-3 FA plus atorvastatin led to significant reductions in serum non-HDL-C (− 9.5% vs 4.7%, P < 0.01), TG (− 21.5% vs 6.2%, P < 0.001) and VLDL-C (− 36.9% vs 4.0%, P < 0.001) and TC (− 6.6% vs 2.1%, P < 0.001). Between the groups, no significant difference in percent change in the serum concentration of LDL-C, HDL-C, as well as in the LDL I and LDL II subclasses was observed. Conclusion: In this group of hyperlipidemic patients on a stable statin prescription, OM3 plus atorvastatin improved small dense LDL concentrations, non-HDL-C, VLDL-C and TG to a greater extent than atorvastatin alone. Further stud- ies are warranted in this area.
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Quantifying the hip-ankle synergy in short-term maximal cyclingSimulation studies have demonstrated that the hip and ankle joints form a task-specific synergy during the downstroke in maximal cycling to enable the power produced by the hip extensor muscles to be transferred to the crank. The existence of the hip-ankle synergy has not been investigated experimentally. Therefore, we sought to apply a modified vector coding technique to quantify the strength of the hip-ankle moment synergy in the downstroke during short-term maximal cycling at a pedalling rate of 135 rpm. Twelve track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm, interspersed with 2 × 4 s seated sprints at 60 rpm on an isokinetic ergometer. Data from the 60 rpm sprints were not analysed in this study. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. The hip-ankle moment synergy was quantified using a modified vector coding method. Results showed, for 28.8% of the downstroke the hip and ankle moments were in-phase, demonstrating the hip and ankle joints tend to work in synergy in the downstroke, providing some support findings from simulation studies of cycling. At a pedalling rate of 135 rpm the hip-phase was most frequent (42.5%) significantly differing from the in- (P = 0.044), anti- (P < 0.001), and ankle-phases (P = 0.004), demonstrating hip-dominant action. We believe this method shows promise to answer research questions on the relative strength of the hip-ankle synergy between different cycling conditions (e.g., power output and pedalling rates).
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Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot StudySarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.
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Small-RNA Sequencing Reveals Altered Skeletal Muscle microRNAs and snoRNAs Signatures in Weanling Male Offspring from Mouse Dams Fed a Low Protein Diet during LactationMaternal diet during gestation and lactation affects the development of skeletal muscles in offspring and determines muscle health in later life. In this paper, we describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction, where dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborns were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in weanling NL male offspring but were not different in the LN group, as compared to NN. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at weaning. Small RNA-sequencing demonstrated DE of multiple miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, -34a, -122 and -199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes. This is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research to unravel the detailed molecular mechanisms.
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MicroRNAs as central regulators of adult myogenesis and proteostasis loss in skeletal muscle ageingSarcopenia (from the Greek words sarca (σάρκα) = flesh and penia (πενία) = deficiency) is considered as an age-associated disease, characterized by dysregulation of the balance between muscle hypertrophy, atrophy and regeneration, which leads to advanced loss of skeletal muscle mass and function associated with a high risk of falls and fractures in the elderly. Numerous studies in humans and animals have explored the pathophysiology of musculoskeletal aging but the detailed mechanisms that contribute to skeletal muscle dysfunction have not been yet fully elucidated. Recently, several studies have focused on the role of microRNAs as a dynamic and promising epigenetic mechanism which may regulate post-transcriptional gene expression that modulate skeletal muscle homeostasis. In this chapter, we describe the crucial role of microRNAs in skeletal myogenesis during adulthood and their association with the pathogenesis of sarcopenia linked to proteostasis loss.
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Age-related changes in microRNAs expression in cruciate ligaments of wild-stock house miceCruciate ligaments (CL) of the knee joint are injured following trauma or aging. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders, but there is little known about the role of miRs and their expression ligaments during aging. This study aimed to (1) identify if mice with normal physical activity, wild-stock house mice are an appropriate model to study age-related changes in the knee joint and (2) investigate the expression of miRs in aging murine cruciate ligaments. Knee joints were collected from 6 and 24 months old C57BL/6 and wild-stock house mice (Mus musculus domesticus) for ligament and cartilage (OARSI) histological analysis. Expression of miR targets in CLs was determined in 6-, 12-, 24-, and 30-month-old wild-stock house mice, followed by the analysis of predicted mRNA target genes and Ingenuity Pathway Analysis. Higher CL and knee OARSI histological scores were found in 24-month-old wild-stock house mice compared with 6- and 24-month-old C57BL/6 and 6-month-old wild-stock house mice (p < 0.05). miR-29a and miR-34a were upregulated in 30-month-old wild-stock house mice in comparison with 6-, 12-, and 24-month-old wild-stock house mice (p < 0.05). Ingenuity Pathway Analysis on miR-29a and 34a targets was associated with inflammation through interleukins, TGFβ and Notch genes, and p53 signaling. Collagen type I alpha 1 chain (COL1A1) correlated negatively with both miR-29a (r = −0.35) and miR-34a (r = −0.33). The findings of this study support wild-stock house mice as an appropriate aging model for the murine knee joint. This study also indicated that miR-29a and miR-34a may be potential regulators of COL1A1 gene expression in murine CLs.
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Are you lookin’ at me? A mixed-methods case study to investigate the influence of coaches’ presence on performance testing outcomes in male academy rugby league playersThe study used a mixed-methods approach to examine how the presence of coaches influenced male academy rugby league players’ performance during physical performance testing. Fifteen male rugby players completed two trials of 20 m sprint, countermovement jump and prone Yo-Yo test; one with only the lead researcher present and a second where the lead researcher conducted the battery with both the club’s lead S&C coach, academy manager, and the first team assistant and head coach present. Players and coaches then completed one-to-one semi-structured interviews to explore their beliefs, attitudes and opinions towards physical performance testing. In all tests, the players’ performance was better when the coaches were present compared to when this was conducted by the sport scientist alone. Interviews revealed performance testing was used by coaches to exercise their power over players to socialise them into a desired culture. Players’ own power was evident through additional effort during testing when coaches were present. Practitioners should ensure consistency in the presence of significant observers during performance testing of male rugby players to minimise their influence on test outcome.
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From dyads to collectives: a review of honeybee signallingThe societies of honeybees (Apis spp) are microcosms of divided labour where the fitness interests of individuals are so closely aligned that, in some contexts, the colony behaves as an entity in itself. Self-organization at this extraordinary level requires sophisticated communication networks, so it is not surprising that the celebrated “waggle dance”, by which bees share information about locations outside the hive, evolved here. Yet bees within the colony respond to several other lesser-known signalling systems, including the tremble dance, the stop signal and the shaking signal, whose roles in coordinating worker behaviour are not yet fully understood. Here, we firstly bring together the large but disparate historical body of work that has investigated the “meaning” of such signals for individual bees, before going on to discuss how network-based approaches can show how such signals function as a complex system to control the collective foraging effort of these remarkable social insect societies.
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Chapter 5: Applying Proteomics to Investigate Extracellular Matrix in Health and DiseaseThe molecular composition of basement membranes (BMs) has traditionally been investigated by candidate-based approaches leading to the identification of key structural components as described in previous chapters. Laminins, collagen IV, nidogens, perlecan, and type XV/XVIII collagen are integral to BMs with isoforms showing tissue specificity. More recently the application of mass spectrometry (MS)-based proteomics has led to the discovery of many more structural and regulatory components of BMs and more broadly, extracellular matrix (ECM). These investigations have revealed tissue-specific signatures of between 100 and 150 ECM components, demonstrating the complexity of the extracellular niche. In addition to providing a structural scaffold for cells, ECM is a dynamic extracellular environment capable of regulating the physical properties of tissues. Global investigations of ECM with proteomics in turn enable systems level analyses and when applied to health and disease states these investigations provide insights into pathways regulating matrix dysregulation. This chapter focuses on the methods used to extract ECM and on the analysis of its composition using MS-based proteomics, and it provides examples of how these approaches have been used to investigate health and disease states.
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Peptide mass fingerprinting of preserved collagen in archaeological fish bones for the identification of flatfish in European watersBones of Pleuronectiformes (flatfish) are often not identified to species due to the lack of diagnostic features on bones that allow adequate distinction between taxa. This hinders in-depth understanding of archaeological fish assemblages and particularly flatfish fisheries throughout history. This is especially true for the North Sea region, where several commercially significant species have been exploited for centuries, yet their archaeological remains continue to be understudied. In this research, 8 peptide biomarkers for 18 different species of Pleuronectiformes from European waters are described using MALDI-TOF MS and LC-MS/MS data obtained from modern reference specimens. Bone samples (n=202) from three archaeological sites in the UK and France dating to the medieval period (c. 7th–16th century CE) were analysed using ZooMS. Of the 201 that produced good quality spectra, 196 were identified as flatfish species, revealing a switch in targeted species through time and indicating that ZooMS offers a more reliable and informative approach for species identification than osteological methods alone. We recommend this approach for future studies of archaeological flatfish remains as the precise species uncovered from a site can tell much about the origin of the fish, where people fished and whether they traded between regions.
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Collagen fingerprinting of Caribbean archaeological fish bones: Methodological implications for historical fisheries baselines and anthropogenic changeThe Caribbean Sea is the most species-rich sea in the Atlantic, largely due to its vast coral reef systems. However, its high biodiversity and endemism face unprecedented anthropogenic threats, including synergistic modern pressures from overfishing, climate change and bioinvasion. Archaeological data indicate initial human settle- ment of the Caribbean ~7000 years before present (yr BP), with regionally variable human impacts on fisheries through time based on standard morphological identification of fish bone. Such studies, however, are challenged by the low taxonomic resolution of archaeological fish bone identifications due to high species diversity and morphological similarity between members of different families or genera. Here, we present collagen finger- printing (Zooarchaeology by Mass Spectrometry; ZooMS) as a method to overcome this challenge, applying it to 1000 archaeological bone specimens identified morphologically as ray-finned fish (superclass Actinopterygii) from 13 circum-Caribbean sites spanning ca. 3150–300 yr BP (years before present). The method successfully identified collagen-containing samples (n = 720) to family (21%), genus (57%), and species (13%) level. Of the 209 samples that were morphologically identified below superclass, collagen fingerprinting verified the taxo- nomic identity of 94% of these, but also refined the identifications to a lower [more precise] taxon in 45% of cases. The remaining 6% of morphological identifications were found to be incorrectly assigned. This study represents the largest application of ZooMS to archaeological fish bones to date and advances future research through the identification of up to 20 collagen biomarkers for 45 taxa in 10 families and 2 orders. The results indicate that refinement of ZooMS archaeological fish identifications in this study is limited not by the quality of the preserved collagen but by the extent of the available modern collagen reference collection. Thus, efforts should be directed towards expanding collagen fingerprint databases in the first instance. Significantly, the high- resolution taxonomic identifications of archaeological bone that ZooMS can offer make ancient fisheries data highly relevant to modern sustainability and conservation efforts in the Caribbean. Additionally, more precise identifications will allow archaeologists to address a variety of questions related to cultural fishing practices and changes in fish stocks through time. This study supports the use of ZooMS as an effective biochemical tool available for mass-taxonomic identification of archaeological fish bone samples spanning century to millennial time scales in the circum-Caribbean.
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From dyads to collectives: a review of honeybee signallingAbstract: The societies of honeybees (Apis spp.) are microcosms of divided labour where the fitness interests of individuals are so closely aligned that, in some contexts, the colony behaves as an entity in itself. Self-organization at this extraordinary level requires sophisticated communication networks, so it is not surprising that the celebrated waggle dance, by which bees share information about locations outside the hive, evolved here. Yet bees within the colony respond to several other lesser-known signalling systems, including the tremble dance, the stop signal and the shaking signal, whose roles in coordinating worker behaviour are not yet fully understood. Here, we firstly bring together the large but disparate historical body of work that has investigated the “meaning” of such signals for individual bees, before going on to discuss how network-based approaches can show how such signals function as a complex system to control the collective foraging effort of these remarkable social insect societies.
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Baseline Behavioral Data and Behavioral Correlates of Disturbance for the Lake Oku Clawed Frog (Xenopus longipes)Animal behavior and welfare science can form the basis of zoo animal management. However, even basic behavioral data are lacking for the majority of amphibian species, and species-specific research is required to inform management. Our goal was to develop the first ethogram for the critically endangered frog Xenopus longipes through observation of a captive population of 24 frogs. The ethogram was applied to produce a diurnal activity budget and to measure the behavioral impact of a routine health check where frogs were restrained. In the activity budget, frogs spent the vast majority of time swimming, resting in small amounts of time devoted to feeding, foraging, breathing, and (in males) amplexus. Using linear mixed models, we found no effect of time of day or sex on baseline behavior, other than for breathing, which had a greater duration in females. Linear mixed models indicated significant effects of the health check on duration of swimming, resting, foraging, feeding, and breathing behaviors for all frogs. This indicates a welfare trade-off associated with veterinary monitoring and highlights the importance of non-invasive monitoring where possible, as well as providing candidates for behavioral monitoring of acute stress. This investigation has provided the first behavioral data for this species which can be applied to future research regarding husbandry and management practices.
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Long term analysis of social structure: evidence of age-based consistent associations in male Alpine ibexDespite its recognized importance for understanding the evolution of animal sociality as well as for conservation, long term analysis of social networks of animal populations is still relatively uncommon. We investigated social network dynamics in males of a gregarious mountain ungulate (Alpine ibex, Capra ibex) over ten years focusing on groups, sub-groups and individuals, exploring the dynamics of sociality over different scales. Despite the social structure changing between seasons, the Alpine ibex population was highly cohesive: fission–fusion dynamics lead almost every male in the population to associate with each other male at least once. Nevertheless, we found that male Alpine ibex showed preferential associations that were maintained across seasons and years. Age seemed to be the most important factor driving preferential associations while other characteristics, such as social status, appeared less crucial. We also found that centrality measures were influenced by age and were also related to individual physical condition. The multi-scale and long-term frame of our study helped us show that ecological constrains, such as resource availability, may play a role in shaping associations in a gregarious species, but they cannot solely explain sociality and preferential association that are likely also to be driven by life-history linked physiological and social needs. Our results highlight the importance of long-term studies based on individually recognizable subjects to help us build on our understanding of the evolution of animal sociality.
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Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladderMutations in leucine-rich-repeats and immunoglobulin-like-domains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.
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Identification of an Altered Matrix Signature in Kidney Aging and DiseaseBackground: Accumulation of extracellular matrix in organs and tissues is a feature of both aging and disease. In the kidney, glomerulosclerosis and tubulointerstitial fibrosis accompany the decline in function, which current therapies cannot address, leading to organ failure. Although histologic and ultrastructural patterns of excess matrix form the basis of human disease classifications, a comprehensive molecular resolution of abnormal matrix is lacking. Methods: Using mass spectrometry–based proteomics, we resolved matrix composition over age in mouse models of kidney disease. We compared the changes in mice with a global characterization of human kidney matrix during aging and to existing kidney disease datasets to identify common molecular features. Results: Ultrastructural changes in basement membranes are associated with altered cell adhesion and metabolic processes and with distinct matrix proteomes during aging and kidney disease progression in mice. Within the altered matrix, basement membrane components (laminins, type IV collagen, type XVIII collagen) were reduced and interstitial matrix proteins (collagens I, III, VI, and XV; fibrinogens; and nephronectin) were increased, a pattern also seen in human kidney aging. Indeed, this signature of matrix proteins was consistently modulated across all age and disease comparisons, and the increase in interstitial matrix was also observed in human kidney disease datasets. Conclusions: This study provides deep molecular resolution of matrix accumulation in kidney aging and disease, and identifies a common signature of proteins that provides insight into mechanisms of response to kidney injury and repair.
