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 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.

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review.

Thyroid cancer's incidence has increased in the last decades, and its diagnosis can be a challenge. Further and complementary testing based in biochemical alterations may be important to correctly identify thyroid cancer and prevent unnecessary surgery. Fourier-transform infrared (FTIR) spectroscopy is a metabolomic technique that has already shown promising results in cancer metabolome analysis of neoplastic thyroid tissue, in the identification and classification of prostate tumor tissues and of breast carcinoma, among others. This work aims to gather and discuss published information on the ability of FTIR spectroscopy to be used in metabolomic studies of the thyroid, including discriminating between benign and malignant thyroid samples and grading and classifying different types of thyroid tumors.

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.