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INTRODUCTION: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear. METHODS: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC‐FID. The MCI subjects were followed up for 58 ± 12.5 months. RESULTS: In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI‐to‐AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI‐to‐AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI‐to‐AD progression, respectively. DISCUSSION: The circulating LFA is involved in the pathogenesis and progression of AD. Highlights: The lipidome fatty acid profile in CSF and plasma was markedly different.Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease.In plasma, higher levels of oleic acid were associated with a reduced risk of MCI‐to‐AD progression.Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI‐to‐AD progression.Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI‐to‐AD progression. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated hepatic steatosis (MAFLD) indicates the metabolic risk associated with hepatic steatosis, overweight and obesity, and clinical evidence of metabolic dysregulation. Since MAFLD is one of the diseases that show a high frequency of alterations in the lipid content of cell membranes, the aim of this study was to evaluate the indices of oxidative damage of erythrocyte membranes in overweight and obese MAFLD subjects. The study was conducted on serum samples and red blood cell membranes of overweight and obese MAFLD subjects. For each patient, biochemical measurements and lipidomic analyses of erythrocytes membranes were performed. Significant differences in fatty acid profiles of RBC membranes were found between overweight and obese patients. In particular, the Peroxidation Index (PI) was higher in the erythrocyte membranes of obese subjects than in overweight subjects. The same behavior was observed for Unsaturation Index (UI) and Free Radical Stress Index (Free RSI), supporting the fact that the systemic increase in oxidative stress was associated with obesity. The study shows that there is a different susceptibility to erythrocyte membrane peroxidation for overweight and obese subjects, and the increased values of oxidative stress indices observed in the erythrocyte membranes of obese patients with MAFLD may be a possible indicator of pro-oxidative events occurring in obesity-related diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Determining the physiological and biochemical causes of aging in animals is important both because of the potential health utility for humans and because aging is related to growth, reproduction processes, and the response of organisms to environmental conditions and stress. It is assumed that the peculiarities of the fatty acid composition of mitochondrial membranes ("membrane-pacemaker" theory of aging) can influence the rate of oxidative damage in cells, as well as the rate of the aging process. This property, in turn, may be fundamental for all living organisms. In this study, the fatty acid composition of gill tissues' mitochondrial membranes, in marine bivalves, was determined and analyzed. The observed features in the lipid composition of mollusk mitochondria correlate well with the longevity of these animals. Marine bivalves belonging to the Mytilidae and Pectinidae Families were used in this research. The specific objectives of this study were: to determine the Fatty Acids (FAs) of mitochondrial gill membranes in bivalves with different lifespans, belonging to the same family, and to calculate their peroxidation index; to compare the levels of ROS generation, malondialdehyde (MDA), and protein carbonyls in the mitochondria of gills, in vitro, during the initiation of free-radical oxation; to investigate whether the FAs of mitochondria gill membranes affect the degree of their oxidative damage and the maximum lifespan of species (MLS). The qualitative membrane lipid composition was uniform in the studied marine bivalves, regardless of their MLS. In terms of the quantitative content of individual FAs, the mitochondrial lipids differed significantly. It is shown that lipid matrix membranes of the mitochondria of long-lived species are less sensitive to in vitro-initiated peroxidation compared with the medium and short-lived species. The differences in MLS are related to the peculiarities of FAs of mitochondrial membrane lipids. [ABSTRACT FROM AUTHOR]

The mitochondrial oxidative stress theory of aging posits that membrane susceptibility to peroxidation and the organization of the electron transport system (ETS) linked with reactive oxygen species (ROS) generation are two main drivers of lifespan. While a clear correlation has been established from species comparative studies, the significance of these characteristics as potential modulators of lifespan divergences among populations of individual species is still to be tested. The bivalve Arctica islandica, the longest-lived non-colonial animal with a record lifespan of 507 years, possesses a lower mitochondrial peroxidation index (PI) and reduced H2O2 efflux linked to complexes I and III activities than related species. Taking advantage of the wide variation in maximum reported longevities (MRL) among 6 European populations (36–507 years), we examined whether these two mitochondrial properties could explain differences in longevity. We report no relationship between membrane PI and MRL in populations of A. islandica, as well as a lack of intraspecific relationship between ETS complex activities and MRL. Individuals from brackish sites characterized by wide temperature and salinity windows had, however, markedly lower ETS enzyme activities relative to citrate synthase activity. Our results highlight environment-dependent remodeling of mitochondrial phenotypes.

Introduction: Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; the role of the lipidome fatty acid profile (LFA) in AD progression remains unclear., Methods: The LFA of plasma and cerebrospinal fluid (CSF) samples from 289 participants (103 AD patients, 92 MCI patients, and 94 controls) was determined by GC-FID. The MCI subjects were followed up for 58 ± 12.5 months., Results: In controls, CSF has a more neuroprotective LFA than plasma. In CSF, a higher content of docosahexaenoic acid was associated with a reduced risk of MCI-to-AD progression. In plasma, higher oleic acid content was associated with lower risk of AD, MCI, and MCI-to-AD progression, whereas higher levels of vaccenic acid and docosahexaenoic acid were associated with greater risk of AD and MCI, and higher rate of MCI-to-AD progression, respectively., Discussion: The circulating LFA is involved in the pathogenesis and progression of AD., Highlights: The lipidome fatty acid profile in CSF and plasma was markedly different. Higher levels of vaccenic acid and lower levels of oleic acid in plasma were associated with greater risk of Alzheimer's disease. In plasma, higher levels of oleic acid were associated with a reduced risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in CSF were associated with a lower risk of MCI-to-AD progression. Higher levels of docosahexaenoic acid in plasma were associated with a greater rate of MCI-to-AD progression., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The mitochondrial oxidative stress theory of aging posits that membrane susceptibility to peroxidation and the organization of the electron transport system (ETS) linked with reactive oxygen species (ROS) generation are two main drivers of lifespan. While a clear correlation has been established from species comparative studies, the significance of these characteristics as potential modulators of lifespan divergences among populations of individual species is still to be tested. The bivalve Arctica islandica , the longest-lived non-colonial animal with a record lifespan of 507 years, possesses a lower mitochondrial peroxidation index (PI) and reduced H2O2 efflux linked to complexes I and III activities than related species. Taking advantage of the wide variation in maximum reported longevities (MRL) among 6 European populations (36–507 years), we examined whether these two mitochondrial properties could explain differences in longevity. We report no relationship between membrane PI and MRL in populations of A. islandica , as well as a lack of intraspecific relationship between ETS complex activities and MRL. Individuals from brackish sites characterized by wide temperature and salinity windows had, however, markedly lower ETS enzyme activities relative to citrate synthase activity. Our results highlight environment-dependent remodeling of mitochondrial phenotypes. [ABSTRACT FROM AUTHOR]

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life.

Membrane acyl (fatty acid) composition of vertebrates varies dependent upon body size, body temperature, developmental stage, phylogeny (endothermic or ectothermic) and diet. These differences often involve increases or decreases in the amount and level of unsaturation of the polyunsaturated fatty acids (PUFA), changes that can readily alter the propensity of membranes to undergo peroxidation. These changes are examined in vertebrates using the peroxidation index (PI), a value that calculates the relative peroxidisability of membranes based on the bisallylic methylene concentration of PUFA. A brief discussion of the relevance of PI to tissue peroxidation is presented (with consideration of antioxidant mechanisms). It is proposed that contrary to the deleterious effect of high levels of peroxidation, that low levels of peroxidation may have a positive effect on growth and metabolism in vertebrates. Practical applications: Potential implications of this work include understanding how vertebrates modulate their metabolism and growth; with changes in body size, as a result of the evolution and development of endothermy, and how ectothermic vertebrates can sustain relatively increased rates of metabolism and growth in cold environments. Membrane fatty acid composition varies amongst vertebrates. This often includes changes in relative amount and unsaturation of polyunsaturated fatty acids (PUFA). Such changes can alter the peroxidisability of membranes (PI) and when combined with membrane density differences could have significant effects on the biology of vertebrates. This idea is investigated in terms of increased basal rates of peroxidation stimulating growth and metabolism. [ABSTRACT FROM AUTHOR]

Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B 6 and B 12 ), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD. [ABSTRACT FROM AUTHOR]

Both basal metabolic rate (BMR) and maximum lifespan potential (MLSP) vary with body size in mammals and birds and it has been suggested that these are mediated through size-related variation in membrane fatty acid composition. Whereas the physical properties of membrane fatty acids affect the activity of membrane proteins and, indirectly, an animal's BMR, it is the susceptibility of those fatty acids to peroxidation which influence MLSP. Although there is a correlation between body size and MLSP, there is considerable MLSP variation independent of body size. For example, among bird families, Galliformes (fowl) are relatively short-living and Psittaciformes (parrots) are unusually long-living, with some parrot species reaching maximum lifespans of more than 100 years. We determined BMR and tissue phospholipid fatty acid composition in seven tissues from three species of parrots with an average MLSP of 27 years and from two species of quails with an average MLSP of 5.5 years. We also characterised mitochondrial phospholipids in two of these tissues. Neither BMR nor membrane susceptibility to peroxidation corresponded with differences in MLSP among the birds we measured. We did find that (1) all birds had lower n-3 polyunsaturated fatty acid content in mitochondrial membranes compared to those of the corresponding tissue, and that (2) irrespective of reliance on flight for locomotion, both pectoral and leg muscle had an almost identical membrane fatty acid composition in all birds. [ABSTRACT FROM AUTHOR]

The long-term effect of selenium supplementation on blood glutathione peroxidase (GSH-Px) activity and plasma TBARS' production (as an index of peroxidation) was evaluated in 15-mo-old male rats fed a diet supplemented with 0.25 or 0.50 ppm selenium, for 12 mo. A group of nonsupplemented age-matched rats was the control. In addition, triglycerides, phospholipids, total and free cholesterol, HDL-cholesterol, and HDL-phospholipid levels were measured in plasma. Plasma testosterone levels were also determined in order to control the aging process in these animals. The GSH-Px activity and the peroxidation level were unchanged in all the groups. However, concerning the lipid parameters, a decrease in triglycerides concentration was observed in both treated groups ( p<0.05). Therefore, in these experimental conditions, despite no observed changes in parameters related to lipid peroxidation, selenium seems to be involved with triglycerides metabolism, eventually improving the triglycerides status of aged animals. [ABSTRACT FROM AUTHOR]

Lipids were determinants in the appearance and evolution of life. Recent studies disclose the existence of a link between lipids and animal longevity. Findings from both comparative studies and genetics and nutritional interventions in invertebrates, vertebrates, and exceptionally long-lived animal species—humans included—demonstrate that both the cell membrane fatty acid profile and lipidome are a species-specific optimized evolutionary adaptation and traits associated with longevity. All these emerging observations point to lipids as a key target to study the molecular mechanisms underlying differences in longevity and suggest the existence of a lipidome profile of long life. [ABSTRACT FROM AUTHOR]

The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids peroxidation index (PI) is negatively correlated with longevity. Long-living marine molluscs are increasingly studied as longevity models, and the presence of different types of lipids in the membranes of these organisms raises questions on the existence of a PI-longevity relationship. We address this question by comparing the longest living metazoan species, the mud clam Arctica islandica (maximum reported longevity = 507 year) to four other sympatric bivalve molluscs greatly differing in longevity (28, 37, 92, and 106 year). We contrasted the acyl and alkenyl chain composition of phospholipids from the mitochondrial membranes of these species. The analysis was reproduced in parallel for a mix of other cell membranes to investigate whether a different PI-longevity relationship would be found. The mitochondrial membrane PI was found to have an exponential decrease with increasing longevity among species and is significantly lower for A. islandica. The PI of other cell membranes showed a linear decrease with increasing longevity among species and was also significantly lower for A. islandica. These results clearly demonstrate that the PI also decreases with increasing longevity in marine bivalves and that it decreases faster in the mitochondrial membrane than in other membranes in general. Furthermore, the particularly low PI values for A. islandica can partly explain this species' extreme longevity. [ABSTRACT FROM AUTHOR]