Phenotypic molecular features of long-lived animal species.

One of the challenges facing science/biology today is uncovering the molecular bases that support and determine animal and human longevity. Nature, in offering a diversity of animal species that differ in longevity by more than 5 orders of magnitude, is the best 'experimental laboratory' to achieve this aim. Mammals, in particular, can differ by more than 200-fold in longevity. For this reason, most of the available evidence on this topic derives from comparative physiology studies. But why can human beings, for instance, reach 120 years whereas rats only last at best 4 years? How does nature change the longevity of species? Longevity is a species-specific feature resulting from an evolutionary process. Long-lived animal species, including humans, show adaptations at all levels of biological organization, from metabolites to genome, supported by signaling and regulatory networks. The structural and functional features that define a long-lived species may suggest that longevity is a programmed biological property.

Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial ß-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.

Selective brain regional changes in lipid profile with human aging.

Fatty acids are key components in the structural diversity of lipids and play a strategic role in the functional properties of lipids which determine the integrity of neuronal and glial cell membranes, the generation of lipid signaling mediators, and the chemical reactivity of acyl chains. The present study analyzes using gas chromatography the fatty acid profiles of 13 regions of the human central nervous system in healthy individuals ranging from 40 to 80 years old. The outcomes suggest the existence of general traits in fatty acid composition such as an average chain length of 18 carbon atoms, high monounsaturated fatty acid content, and predominance in polyunsaturated fatty acids of those of series n-6 over series n-3 which are shared by all brain regions regardless of age. Our results also show a general sustained and relatively well-preserved lipid profile throughout the adult lifespan in most studied regions (olive, upper vermis, substantia nigra, thalamus, hippocampus, putamen, caudate, occipital cortex, parietal cortex, entorhinal cortex, and frontal cortex) with minor changes that are region-dependent. In contrast, of particular relevance is the involvement of the inferior temporal cortex and cingulate cortex. It is proposed that during normal human brain aging, the lipid profile is resistant to changes with age in most human brain regions to ensure cell survival and function, but some particular regions involved in specific memory domains are greatly affected.

In rats fed high-energy diets, taste, rather than fat content, is the key factor increasing food intake: a comparison of a cafeteria and a lipid-supplemented standard diet.

BACKGROUND: Food selection and ingestion both in humans and rodents, often is a critical factor in determining excess energy intake and its related disorders. METHODS: Two different concepts of high-fat diets were tested for their obesogenic effects in rats; in both cases, lipids constituted about 40% of their energy intake. The main difference with controls fed standard lab chow, was, precisely, the lipid content. Cafeteria diets (K) were self-selected diets devised to be desirable to the rats, mainly because of its diverse mix of tastes, particularly salty and sweet. This diet was compared with another, more classical high-fat (HF) diet, devised not to be as tasty as K, and prepared by supplementing standard chow pellets with fat. We also analysed the influence of sex on the effects of the diets. RESULTS: K rats grew faster because of a high lipid, sugar and protein intake, especially the males, while females showed lower weight but higher proportion of body lipid. In contrast, the weight of HF groups were not different from controls. Individual nutrient's intake were analysed, and we found that K rats ingested large amounts of both disaccharides and salt, with scant differences of other nutrients' proportion between the three groups. The results suggest that the key differential factor of the diet eliciting excess energy intake was the massive presence of sweet and salty tasting food. CONCLUSIONS: The significant presence of sugar and salt appears as a powerful inducer of excess food intake, more effective than a simple (albeit large) increase in the diet's lipid content. These effects appeared already after a relatively short treatment. The differential effects of sex agree with their different hedonic and obesogenic response to diet.