FTIR Spectroscopy and Blood-Derived Extracellular Vesicles Duo in Alzheimer's Disease.

Background: Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids. Objective: The aim of this study was to identify blood-derived EVs (bdEVs) spectroscopic signatures with AD discriminatory potential. Methods: Herein, FTIR spectra of bdEVs from two biofluids (serum and plasma) and distinct sets of Controls and AD cases were acquired, and EVs' spectra analyzed. Results: Analysis of bdEVs second derivative peaks area revealed differences between Controls and AD cases in distinct spectra regions, assigned to carbohydrates and nucleic acids, amides, and lipids. Conclusions: EVs' spectroscopic profiles presented AD discriminatory value, supporting the use of bdEVs combined with FTIR as a screening or complementary tool for AD diagnosis.

Home- versus centre-based EXercise InTervention in patients with Heart Failure (EXIT-HF trial): A pragmatic randomized controlled trial.

INTRODUCTION: The limited accessibility and the lack of adherence explain, in part, the low proportion of heart failure (HF) patients undergoing exercise-based cardiac rehabilitation (CR) programs. Home-based programs showed to be as effective and less costly than centre-based ones and might address those obstacles. Whether the evidence from international studies can be applied to our population is still unclear. OBJECTIVES: To compare the clinical and economic impact of a home-based versus centre-based CR intervention in HF patients. METHODS: This is a single-center, single-blind, parallel groups, non-inferiority pragmatic randomized control trial. Adult HF patients (n=120) will be randomized to either a centre-based or home-based CR program. In both groups' patients will participate in a 12-week combined CR program with 2 sessions per week. Exercise training (ExT) protocol consists of a combination of endurance [(at 60%-80% of peak oxygen uptake (VO2peak)] and resistance training (elastic bands). Those allocated to the home-based program will start with 4-5 supervised ExT sessions to familiarize themselves with the training protocol and then will continue the remaining sessions at home. The primary endpoint is the change in VO2peak at the end of the 12-week program. Secondary outcomes include alterations in circulating biomarkers, physical fitness, physical activity, quality of life, diet, psychological wellbeing, dyspnea, and cost-effectiveness analyses. RESULTS: Patients are currently being recruited for the study. The study started in November 2019 and data collection is anticipated to be completed by December 2022. This is the first study in Portugal comparing the traditional CR program with a home-based program in HF patients. Our study results will better inform healthcare professionals who care for HF patients regarding CR.

Evaluation of Probable Sarcopenia's Prevalence in Hospitalized Geriatric Patients Using Ishii's Score.

BACKGROUND: Sarcopenia is defined as a progressive loss of skeletal muscle mass and strength related to age and comorbidities. Worldwide sarcopenia's prevalence varies between 10-40%, being associated with functional impairment, lower quality of life, and higher mortality. Sarcopenia can be estimated based on age, calf circumference, and handgrip strength (Ishii's formula). Early diagnosis is essential because treatment with nutritional support and rehabilitation programs can prevent complications. The aim of the study was to assess the prevalence of probable sarcopenia in hospitalized patients using Ishii's score and possible associated risk factors. METHODS: We developed an observational prospective study in a medicine inpatient ward of a Central Hospital. We applied Ishii's formula to the patients admitted to the medical ward in December 2021 and January 2022. Patients should be aged 60 or above and able to collaborate with the tests. One year later, we analyzed re-hospitalization and mortality rates. Patients with edema of the lower limbs, who were not able to follow instructions, and who were admitted exclusively for symptomatic treatment were excluded. RESULTS: Our final sample was 49 patients (55% males, mean age 78 ± 8.88 years). Only one patient had a previous diagnosis of sarcopenia. Estimated sarcopenia´s prevalence was 73.5% N=36), higher in men and people with three or more comorbidities. In the sarcopenic group, 77% had some degree of functional dependency and positive markers for malnutrition. After one year of follow-up, we found a higher mortality rate in the sarcopenic group (44.4% against 7.6%) and a higher number of re-hospitalizations (1.03 hospitalizations per patient, against 0.31). CONCLUSIONS: Our data showed that the prevalence of probable sarcopenia is high, but this pathology is still underdiagnosed. Traditional diagnosis is complex in some hospital settings and a simple tool such as Ishii's score can help to improve diagnostic rates. We suggest screening all patients at admission to provide early rehabilitation and nutritional support.

A Canadian case control study investigating demographic and environmental factors associated with MOGAD.

BACKGROUND: Little is known about demographic and environmental factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). OBJECTIVE: To investigate factors associated with MOGAD using a case-control design and validated questionnaire from the Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS). METHODS: We enrolled patients with positive MOG antibody serology and diagnosis of MOGAD at six Canadian centres. MOGAD participants completed the EnvIMS questionnaire, and were compared to unaffected controls from the Canadian arm of EnvIMS. We calculated crude and adjusted odds ratios (OR) using logistic regression models and Firth's procedure for rare events. RESULTS: We enrolled 39 MOGAD participants with mean (SD) age 45.0 (14.4) years, 28 (71.8 %) women, 25 (64.1 %) White, 26 (66.7 %) residents of Ontario, and mean BMI 28.6 (7.1). They were compared to 956 controls. Using multivariable logistic regression, larger body size at age 10 years (OR: 3.57, 95 % CI:1.23 - 10.33) and non-White ethnicity (OR:3.81, 95 % CI:1.93-7.54) were associated with higher odds of MOGAD. Among Ontario residents, current BMI ≥30 was associated with higher odds of MOGAD (OR:2.79, 95 % CI:1.03-7.53). CONCLUSION: Our findings are hypothesis-generating due to the sample size, but suggest that obesity and ethnicity should be explored as potential risk factors for MOGAD in other settings.

Projected health and economic outcomes of extending public funding of pharmacy services to include administration of Pneu23 and Td/Tdap immunizations by pharmacy practitioners in New Brunswick.

Background: Although legislation permits New Brunswick pharmacy professionals to administer a wide range of immunizations, public funding for these services is currently limited to immunizations against influenza and COVID-19 and was recently extended to include pneumococcal immunization (Pneu23) in individuals aged 65 years or older. We used administrative data to project health and economic outcomes associated with the current Pneu23 program and with extension of public funding to include: 1) younger adults aged 19 years or older in the Pneu23 program, and 2) tetanus boosters (Td/Tdap). Methods: Two model scenarios were compared: a Physician-Only model in which physicians remain the only practitioners to administer publicly funded Pneu23 and Td/Tdap, and a Blended model in which this service is also provided by pharmacy professionals. Immunization rates by practitioner type were projected based on physician billing data accessed via the New Brunswick Institute for Research, Data and Training in conjunction with trends observed with influenza immunization by pharmacists. These projections were used along with published data to estimate health and economic outcomes under each model. Results: Public funding of Pneu23 (65+), Pneu23 (19+) and Td/Tdap (19+) administration by pharmacy professionals is projected to yield increased immunization rates and physician time savings compared with the Physician-Only model. Public funding of Pneu23 and Td/Tdap administration by pharmacy professionals in those aged ≥19 years would result in cost savings, owing primarily to productivity losses avoided in the working age population. Discussion: Increased immunization rates, physician time savings and cost savings may be realized if public funding were extended to include administration of Pneu23 in younger adults and Td/Tdap, by pharmacy practitioners.

Metabolomics to Study Human Aging: A Review.

In the last years, with the increase in the average life expectancy, the world's population is progressively aging, which entails social, health and economic problems. In this sense, the need to better understand the physiology of the aging process becomes an urgent need. Since the study of aging in humans is challenging, cellular and animal models are widely used as alternatives. Omics, namely metabolomics, have emerged in the study of aging, with the aim of biomarker discovering, which may help to uncomplicate this complex process. This paper aims to summarize different models used for aging studies with their advantages and limitations. Also, this review gathers the published articles referring to biomarkers of aging already discovered using metabolomics approaches, comparing the results obtained in the different studies. Finally, the most frequently used senescence biomarkers are described, along with their importance in understanding aging.

The Canadian Longitudinal Study on Aging: A Vehicle for Research on Aging in Older Veterans.

INTRODUCTION: Research on the health of older Veterans in Canada is an emerging area. Few population-based studies in Canada have included older Veterans as a specific group of interest. This paper describes a cohort of self-identified Veterans within the Canadian Longitudinal Study on Aging (CLSA). MATERIALS AND METHODS: Using data from the CLSA baseline assessment (2011-2015), we describe sociodemographic and health characteristics along with military-related variables in a cohort of Veterans in Canada. We also estimate the number of Canadian and non-Canadian Veterans living in Canada at the time of the CLSA baseline data collection. RESULTS: We estimate that at the CLSA baseline, there were 718,893 (95% confidence interval [CI], 680,033-757,110) Canadian Veterans and 185,548 (95% CI, 165,713-205,100) non-Canadian Veterans aged 45-85 years living in Canada. Veterans were older and predominantly male compared to non-Veterans in the CLSA. Following age and sex adjustment, the distribution of sociodemographic and health characteristics was similar across all groups. The majority (> 85%) of participants in each comparison group reported self-rated general and mental health as excellent, very good, or good. Following age and sex adjustment, most characteristics across groups remained similar. One exception was mental health, where a greater proportion of Veterans screened positive for depression and anxiety relative to non-Veterans. CONCLUSIONS: Using CLSA baseline data, we estimate the number of older Veterans in Canada and present descriptive data that highlight interesting differences and similarities between Veterans and non-Veterans living in Canada. Canadian and non-Canadian Veterans in the CLSA are presented separately, with the latter group having not been previously studied in Canada. This paper presents a snapshot of a cohort of self-identified Veterans within the CLSA at study baseline and highlights the potential of the CLSA as a vehicle for studying the aging Veteran population in Canada for years to come.

Impaired Extracellular Proteostasis in Patients with Heart Failure.

BACKGROUND: Proteostasis impairment and the consequent increase of amyloid burden in the myocardium have been associated with heart failure (HF) development and poor prognosis. A better knowledge of the protein aggregation process in biofluids could assist the development and monitoring of tailored interventions. AIM: To compare the proteostasis status and protein's secondary structures in plasma samples of patients with HF with preserved ejection fraction (HFpEF), patients with HF with reduced ejection fraction (HFrEF), and age-matched individuals. METHODS: A total of 42 participants were enrolled in 3 groups: 14 patients with HFpEF, 14 patients with HFrEF, and 14 age-matched individuals. Proteostasis-related markers were analyzed by immunoblotting techniques. Fourier Transform Infrared (FTIR) Spectroscopy in Attenuated Total Reflectance (ATR) was applied to assess changes in the protein's conformational profile. RESULTS: Patients with HFrEF showed an elevated concentration of oligomeric proteic species and reduced clusterin levels. ATR-FTIR spectroscopy coupled with multivariate analysis allowed the discrimination of HF patients from age-matched individuals in the protein amide I absorption region (1700-1600 cm-1), reflecting changes in protein conformation, with a sensitivity of 73 and a specificity of 81%. Further analysis of FTIR spectra showed significantly reduced random coils levels in both HF phenotypes. Also, compared to the age-matched group, the levels of structures related to fibril formation were significantly increased in patients with HFrEF, whereas the ß-turns were significantly increased in patients with HFpEF. CONCLUSION: Both HF phenotypes showed a compromised extracellular proteostasis and different protein conformational changes, suggesting a less efficient protein quality control system.

A national case-control study investigating demographic and environmental factors associated with NMOSD.

BACKGROUND: Risk factors for aquaporin-4 (AQP4+) antibody neuromyelitis optica spectrum disorder (NMOSD) are not well-established. OBJECTIVE: To investigate demographic and environmental factors associated with NMOSD using a validated questionnaire and case-control design. METHODS: We enrolled patients with AQP4 + NMOSD through six Canadian Multiple Sclerosis Clinics. Participants completed the validated Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS) questionnaire. Their responses were compared to those of 956 unaffected controls from the Canadian arm of EnvIMS. We calculated odds ratios (ORs) for the association between each variable and NMOSD using logistic regression and Firth's procedure for rare events. RESULTS: In 122 participants (87.7% female) with NMOSD, odds of NMOSD in East Asian and Black participants were ⩾8 times that observed in White participants. Birthplace outside Canada was associated with an increased risk of NMOSD (OR = 5.5, 95% confidence interval (CI) = 3.6-8.3) as were concomitant autoimmune diseases (OR = 2.7, 95% CI = 1.4-5.0). No association was observed with reproductive history or age at menarche. CONCLUSION: In this case-control study, risk of NMOSD in East Asian and Black versus White individuals was greater than that observed in many previous studies. Despite the preponderance of affected women, we did not observe any association with hormonal factors such as reproductive history or age at menarche.

Prevalence of Frailty Among Hospitalized Older Adults in New Brunswick, Canada: an Administrative Data Population-Based Study.

Background: Characterizing the prevalence and distribution of frailty within a population can help guide decision-making and policy development by identifying health service resource needs. Here we describe the prevalence of frailty among hospitalized older adults in New Brunswick (NB), Canada. Methods: NB administrative hospital claims data were used to identify hospitalized older adults aged 65 or older between April 1, 2017 and March 31, 2019. Frailty was quantified using the Hospital Frailty Risk Score (HFRS), a validated frailty tool derived from claims data. Individuals with a HFRS ranked as intermediate or high were categorized as frail. The distribution of frailty across sex and age are described. Crude prevalence estimates and corresponding 95% confidence intervals are presented. Results: A total of 55,675 older adults (52% females) were hospitalized. The overall prevalence of frailty was 21.2% (95%CI: 20.9-21.6). Prevalence increased with age: 12.7% (95%CI: 12.3-13.1) in the 65-74 age group, 24.7% (95%CI: 24.1-25.3) in the 75-84 age group and 41.6% (95%CI: 40.6-42.7) for those aged 85 and over (p<.001). Discussion/Conclusion: The distribution of frailty is in line with that reported in other jurisdictions. We demonstrate the feasibility of the HFRS to identify and characterize frailty in a large sample of older adults who were hospitalized, using administrative data.

Clinical Determinants and Barriers to Cardiac Rehabilitation Enrollment of Patients with Heart Failure with Reduced Ejection Fraction: A Single-Center Study in Portugal.

Despite cardiac rehabilitation (CR) being a recommended treatment for patients with heart failure with reduced ejection fraction (HFrEF), it is still underused. This study investigated the clinical determinants and barriers to enrollment in a CR program for HFrEF patients. We conducted a cohort study using the Cardiac Rehabilitation Barriers Scale (CRBS) to assess the reason for non-enrollment. Of 214 HFrEF patients, 65% had not been enrolled in CR. Patients not enrolled in CR programs were older (63 vs. 58 years; p < 0.01) and were more likely to have chronic obstructive pulmonary disease (COPD) (20% vs. 5%; p < 0.01). Patients enrolled in CR were more likely to be treated with sacubitril/valsartan (34% vs. 19%; p = 0.01), mineralocorticoid receptor antagonists (84% vs. 72%; p = 0.04), an implantable cardioverter defibrillator (ICD) (41% vs. 20%; p < 0.01), and cardiac resynchronization therapy (21% vs. 10%; p = 0.03). Multivariate analysis revealed that age (adjusted OR 1.04; 95% CI 1.01−1.07), higher education level (adjusted OR 3.31; 95% CI 1.63−6.70), stroke (adjusted OR 3.29; 95% CI 1.06−10.27), COPD (adjusted OR 4.82; 95% CI 1.53−15.16), and no ICD status (adjusted OR 2.68; 95% CI 1.36−5.26) were independently associated with CR non-enrollment. The main reasons for not being enrolled in CR were no medical referral (31%), concomitant medical problems (28%), patient refusal (11%), and geographical distance to the hospital (9%). Despite the relatively high proportion (35%) of HFrEF patients who underwent CR, the enrollment rate can be further improved. Innovative multi-level strategies addressing physicians' awareness, patients' comorbidities, and geographical issues should be pursued.

A protocol for a randomized controlled trial comparing Sleepwell, EMPOWER, and treatment-as-usual for benzodiazepine receptor agonist discontinuation in older adults: the your answers when needing sleep in New Brunswick (YAWNS NB) study.

Background: Chronic benzodiazepine receptor agonist (BZRA) use among older adults is a public health concern given cognitive and physical risks. One in four older adults in New Brunswick, Canada, is a long-term user of BZRAs. Previous studies using a direct-to-patient approach as the primary intervention target have shown promise in reducing BZRA use. The Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study aims to reduce the long-term use of BZRAs in older adults and increase the use of cognitive behavioural therapy for insomnia (CBTi), which is the recommended first line treatment. Methods: The trial (ClinicalTrials.gov registration NCT04406103) is a three arm, open-label, parallel randomized controlled trial in NB, Canada. Eligible participants 65 years and older using BZRAs long-term will be randomly allocated to: the Eliminating Medications through Patient Ownership of End Results (EMPOWER) information package group; the Sleepwell information package group; or treatment-as-usual (TAU). Information packages will be mailed via Canada Post. The primary outcome of BZRA discontinuation at 6 months will be compared across groups. Secondary outcomes include participants with ≥25% BZRA dose reduction, and switching to newly prescribed alternate sedative-hypnotics. Several exploratory outcomes will also be examined. Discussion: Targeting participants with information packages informing them of appropriate use, dangers, and approaches to reducing BZRA use and increasing CBTi use may be beneficial in a region of Canada with the highest rate of chronic BZRA use in older adults. Comparing information packages and TAU will provide insights into the effectiveness of direct-to-patient interventions for BZRA reduction.

eHealthResp, a Digital Intervention to Improve Antibiotic Prescribing in Respiratory Infections: A Pilot Study.

The emergence of antibiotic resistance (ABR) is one of the most serious public health threats worldwide. The inappropriate use of antibiotics is considered the main determinant for the increase and development of ABR, contributing to a greater risk of therapeutic ineffectiveness, particularly within primary care context. Therefore, this pilot study aims to raise awareness and promote an adequate antibiotic use among physicians, through the evaluation of the eHealthResp platform, a digital intervention composed by an online course and a mobile application, to aid in the management of respiratory tract infections. The global validation of the eHealthResp platform was carried out by 12 physicians who explored and performed a quantitative and qualitative evaluation of the contents of the online course and mobile app. The global evaluation of the analyzed parameters was very positive, with the highest median scores being attributed to adequacy, correction, format, and trust of the eHealthResp platform. The qualitative feedback enhanced the contents' relevance, clarity, and consolidation, as well as the effectiveness of the educational intervention against ABR. Overall, this study revealed that the eHealthResp may be regarded as an important e-health tool for the management of respiratory tract infections and improvement of antibiotic prescription practices among physicians.

Improving Pharmacists' Awareness of Inadequate Antibiotic Use for URTIs through an Educational Intervention: A Pilot Study.

The inadequate use of antibiotics led to the development of multi-resistant bacteria that are now causing millions of deaths worldwide. Since most antibiotics are prescribed/dispensed to treat respiratory tract infections, it is important to raise awareness among health professionals to optimize antibiotic use, especially within the primary care context. Thus, this pilot study aimed to evaluate pharmacists' feedback about the eHealthResp platform, composed by an online course and a mobile application (app) to help in the management of upper respiratory tract infections (URTIs). Ten community pharmacists were invited to participate in this study, exploring the contents of the eHealthResp platforms and answering a content validation questionnaire composed by eight qualitative and thirty-five quantitative questions about the online course and mobile app. The eHealthResp platform is a comprehensive, consistent, and high-quality e-learning tool. Median scores of 5.00 were attributed to the course contents' and clinical cases' adequacy and correction. Most qualitative feedback was about completeness and objectivity of the course, and its usefulness for clinical practice. This study showed that eHealthResp has great potential as an e-health tool for the management of URTIs' symptoms, which may ultimately aid in reducing inappropriate antibiotic use.

The Long-Term Culture of Human Fibroblasts Reveals a Spectroscopic Signature of Senescence.

Aging is a complex process which leads to progressive loss of fitness/capability/ability, increasing susceptibility to disease and, ultimately, death. Regardless of the organism, there are some features common to aging, namely, the loss of proteostasis and cell senescence. Mammalian cell lines have been used as models to study the aging process, in particular, cell senescence. Thus, the aim of this study was to characterize the senescence-associated metabolic profile of a long-term culture of human fibroblasts using Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. We sub-cultivated fibroblasts from a newborn donor from passage 4 to passage 17 and the results showed deep changes in the spectroscopic profile of cells over time. Late passage cells were characterized by a decrease in the length of fatty acid chains, triglycerides and cholesterol and an increase in lipid unsaturation. We also found an increase in the content of intermolecular ß-sheets, possibly indicating an increase in protein aggregation levels in cells of later passages. Metabolic profiling by NMR showed increased levels of extracellular lactate, phosphocholine and glycine in cells at later passages. This study suggests that spectroscopy approaches can be successfully used to study changes concomitant with cell senescence and validate the use of human fibroblasts as a model to monitor the aging process.

Proteostasis Response to Protein Misfolding in Controlled Hypertension.

Hypertension is the most determinant risk factor for cardiovascular diseases. Early intervention and future therapies targeting hypertension mechanisms may improve the quality of life and clinical outcomes. Hypertension has a complex multifactorial aetiology and was recently associated with protein homeostasis (proteostasis). This work aimed to characterize proteostasis in easy-to-access plasma samples from 40 individuals, 20 with controlled hypertension and 20 age- and gender-matched normotensive individuals. Proteostasis was evaluated by quantifying the levels of protein aggregates through different techniques, including fluorescent probes, slot blot immunoassays and Fourier-transform infrared spectroscopy (FTIR). No significant between-group differences were observed in the absolute levels of various protein aggregates (Proteostat or Thioflavin T-stained aggregates; prefibrillar oligomers and fibrils) or total levels of proteostasis-related proteins (Ubiquitin and Clusterin). However, significant positive associations between Endothelin 1 and protein aggregation or proteostasis biomarkers (such as fibrils and ubiquitin) were only observed in the hypertension group. The same is true for the association between the proteins involved in quality control and protein aggregates. These results suggest that proteostasis mechanisms are actively engaged in hypertension as a coping mechanism to counteract its pathological effects in proteome stability, even when individuals are chronically medicated and presenting controlled blood pressure levels.

Identifying children with medical complexity in administrative datasets in a Canadian context: study protocol.

INTRODUCTION: Children with medical complexity and their families are an important population of interest within the Canadian healthcare system. Despite representing less than 1% of the paediatric population, children with medical complexity require extensive care and account for one third of paediatric healthcare expenditures. Opportunities to conduct research to assess disparities in care and appropriate allocation of health resources relies on the ability to accurately identify this heterogeneous group of children. This study aims to better understand the population of children with medical complexity in the Canadian Maritimes, including Nova Scotia (NS), New Brunswick (NB) and Prince Edward Island (PEI). This will be achieved through three objectives: (1) Evaluate the performance of three algorithms to identify children with medical complexity in the Canadian Maritimes in administrative data; then using the 'best fit' algorithm (2) Estimate the prevalence of children with medical complexity in the Canadian Maritimes from 2003 to 2017 and (3) Describe patterns of healthcare utilisation for this cohort of children across the Canadian Maritimes. METHODS AND ANALYSIS: The research will be conducted in three phases. In Phase 1, an expert panel will codevelop a gold-standard definition of paediatric medical complexity relevant to the Canadian Maritime population. A two-gate validation process will then be conducted using NS data and the gold-standard definition to determine the 'best fit' algorithm. During phase 2 the 'best fit' algorithm will be applied to estimate the prevalence of children with medical complexity in NS, NB and PEI. Finally, in phase 3 will describe patterns of healthcare utilisation across the Canadian Maritimes. ETHICS AND DISSEMINATION: Ethics approval for this protocol was granted by the institutional research ethics board at the IWK Health Centre (REB # 1026245). A waiver of consent was approved. This study will use an integrated knowledge translation approach, where end users are involved in each stage of the project, which could increase uptake of the research into policy and practice. The findings of this research study will be submitted for publication and dissemination through conference presentations and with our end users.

FTIR Spectroscopy as a Tool to Study Age-Related Changes in Cardiac and Skeletal Muscle of Female C57BL/6J Mice.

Studying aging is important to further understand the molecular mechanisms underlying this physiological process and, ideally, to identify a panel of aging biomarkers. Animals, in particular mice, are often used in aging studies, since they mimic important features of human aging, age quickly, and are easy to manipulate. The present work describes the use of Fourier Transform Infrared (FTIR) spectroscopy to identify an age-related spectroscopic profile of the cardiac and skeletal muscle tissues of C57BL/6J female mice. We acquired ATR-FTIR spectra of cardiac and skeletal muscle at four different ages: 6; 12; 17 and 24 months (10 samples at each age) and analyzed the data using multivariate statistical tools (PCA and PLS) and peak intensity analyses. The results suggest deep changes in protein secondary structure in 24-month-old mice compared to both tissues in 6-month-old mice. Oligomeric structures decreased with age in both tissues, while intermolecular ß-sheet structures increased with aging in cardiac muscle but not in skeletal muscle. Despite FTIR spectroscopy being unable to identify the proteins responsible for these conformational changes, this study gives insights into the potential of FTIR to monitor the aging process and identify an age-specific spectroscopic signature.

Fourier-Transform Infrared Spectroscopy as a Discriminatory Tool for Myotonic Dystrophy Type 1 Metabolism: A Pilot Study.

Myotonic dystrophy type 1 (DM1) is a hereditary disease characterized by progressive distal muscle weakness and myotonia. Patients with DM1 have abnormal lipid metabolism and a high propensity to develop a metabolic syndrome in comparison to the general population. It follows that metabolome evaluation in these patients is crucial and may contribute to a better characterization and discrimination between DM1 disease phenotypes and severities. Several experimental approaches are possible to carry out such an analysis; among them is Fourier-transform infrared spectroscopy (FTIR) which evaluates metabolic profiles by categorizing samples through their biochemical composition. In this study, FTIR spectra were acquired and analyzed using multivariate analysis (Principal Component Analysis) using skin DM1 patient-derived fibroblasts and controls. The results obtained showed a clear discrimination between both DM1-derived fibroblasts with different CTG repeat length and with the age of disease onset; this was evident given the distinct metabolic profiles obtained for the two groups. Discrimination could be attributed mainly to the altered lipid metabolism and proteins in the 1800-1500 cm-1 region. These results suggest that FTIR spectroscopy is a valuable tool to discriminate both DM1-derived fibroblasts with different CTG length and age of onset and to study the metabolomic profile of patients with DM1.

Study Aging by Fibroblasts Metabolome.

Aging is a complex multifactorial process that, although universal, is not fully understood. It is known that the impact of aging on health is influenced by multiple factors, such as sex, race, income, and education, and that age-related diseases are strongly associated with the way people get old. The knowledge of biological aging and its comparison to the chronological age is a paramount contributor to predict the metabolic decline and the onset of age-related diseases. As aging processes observed in the whole human organism are somehow the reflection of what happens in each cell type, it is possible to study the aging process using cell lines, such as fibroblasts. Metabolomics analysis of cell lines, namely fibroblasts, gives inputs to personalized or integrative medicine; in fact, cell metabolomics is an emerging field that addresses fundamental biological and metabolic questions using modern "omic" techniques as FTIR, NMR or MS. This paper revises the relevance of using fibroblasts as cell models to study the metabolome of aging.