Membrane lipids and maximum lifespan in clownfish.

The longevity-homeoviscous adaptation (LHA) theory of ageing states that lipid composition of cell membranes is linked to metabolic rate and lifespan, which has been widely shown in mammals and birds but not sufficiently in fish. In this study, two species of the genus Amphiprion (Amphiprion percula and Amphiprion clarkii, with estimated maximum lifespan potentials [MLSP] of 30 and 9-16 years, respectively) and the damselfish Chromis viridis (estimated MLSP of 1-2 years) were chosen to test the LHA theory of ageing in a potential model of exceptional longevity. Brain, livers and samples of skeletal muscle were collected for lipid analyses and integral part in the computation of membrane peroxidation indexes (PIn) from phospholipid (PL) fractions and PL fatty acid composition. When only the two Amphiprion species were compared, results pointed to the existence of a negative correlation between membrane PIn value and maximum lifespan, well in line with the predictions from the LHA theory of ageing. Nevertheless, contradictory data were obtained when the two Amphiprion species were compared to the shorter-lived C. viridis. These results along with those obtained in previous studies on fish denote that the magnitude (and sometimes the direction) of the differences observed in membrane lipid composition and peroxidation index with MLSP cannot explain alone the diversity in longevity found among fishes.

Age-related changes in mitochondrial membrane composition of Nothobranchius furzeri.: comparison with a longer-living Nothobranchius species.

Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates. Mitochondrial PLs showed several changes with age. Proportions of total PLs and PC were reduced while an increase in PS, CL and PE was observed, mainly between the 2.5 and 5 months of fish age, the time during which animals doubled their weight. FA compositions of individual PLs in mitochondria were also significantly affected with age suggesting the existence of increasing damage to mitochondrial lipids during the life-cycle of N. furzeri that could be one of the main contributors to degraded mitochondrial function associated with aging. The peroxidation index values from N. furzeri mitochondrial PLs were significantly lower than those reported in N. rachovii, a species with a twofold longer life span than N. furzeri, which seems to contradict the membrane pacemaker theory of animal metabolism.

Circadian activity rhythms during the last days of Nothobranchius rachovii's life: a descriptive model of circadian system breakdown.

Several studies have been performed to identify age-related changes in the circadian system (CS) but the impairment of the CS and its chronodisruption at the end of an organism life have not been studied in depth. Aging commonly affects the input pathways into the biological clock or restraints their processing, therefore simplifying the system output, the overt rhythms. The purpose of this work was to do a complete characterization of changes that occurs in the CS in the last stage of a vertebrate organism life and to develop tools able to detect in which moment of the last days of life is the animal, using an overt rhythm, the rest-activity rhythm (RAR). For that, a fish species proposed as model for aging studies, Nothobranchius rachovii, has been used. A progressive and sequential CS breakdown has been described for the last 22 d of life of N. rachovii (∼7% of total life), suffering a general RAR impairment mainly reflected by changes in phase regularity, complexity, amplitude and the ability to stay synchronized to the LD cycle. Also, an equation of days remaining of life, based on the RAR description, has been calculated and proposed as a tool to identify close-to-death individuals which could be subjected to an adequate restoring treatment to enhance the CS function and improve their well-being.

Nothobranchius as a model for aging studies. A review.

In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging.

Age-related changes in mitochondrial membrane composition of Nothobranchius rachovii.

Mitochondrial membrane composition may be a critical factor in the mechanisms of the aging process by influencing the propagation of reactions involved in mitochondrial function during periods of high stress. Changes affecting either lipid class or fatty acid compositions could affect phospholipid properties and alter mitochondrial function and cell viability. In the present study, mitochondrial membrane phospholipid compositions were analyzed throughout the life cycle of Nothobranchius rachovii. Mitochondrial phospholipids showed several changes with age. Proportions of cardiolipin decreased and those of sphingomyelin increased between 11- and 14-month-old fish. Fatty acid compositions of individual phospholipids in mitochondria were also significantly affected with age. These data suggest increasing damage to mitochondrial lipids during the life cycle of N. rachovii that could be one of the main factors related with and contributing to degraded mitochondrial function associated with the aging process.

Rest-activity circadian rhythms in aged Nothobranchius korthausae. The effects of melatonin.

Adult (48-week-old) and senescent (72-week-old) individually-kept Nothobranchius korthausae were used as experimental subjects to characterise circadian system (CS) function and age-related changes in senescent fish. This species was specifically chosen because it has already shown potential for use as a model system in gerontological studies. The rest-activity rhythm (RAR) in fish can be easily monitored and used to characterise the state of the CS, and it has also been proposed as a reliable model to study sleep-like periods in fish. As they aged, N. korthausae experienced a significant decrease in total daily activity and a progressive impairment of the RAR, accompanied by changes in the regularity, fragmentation and amplitude of the rhythm. The ability of the CS to oscillate autonomously when the two main synchronizers, photoperiod and feeding time, were absent (continuous darkness and random feeding), was also impaired with age, as the capacity to re-synchronise to the light-dark (LD) cycle declined. Melatonin treatment improved the regularity, fragmentation and amplitude of the RAR in senescent fish, and it also improved sleep efficiency. In conclusion, N. korthausae represents a viable model for studying the aging of the circadian system and the restorative effect of chronobiotic substances, such as melatonin.

La cronodisrupción como causa de envejecimiento / Chronodisruption and ageing

La sociedad actual favorece un modo de vida con mayor actividad nocturna, disminución de las horas de sueño y, en ocasiones, desplazamientos horarios (tales como jet lag o trabajo a turnos) que generan cronodisrupción (CD), la cual puede conducir a un envejecimiento prematuro. La CD se define como una alteración relevante del orden temporal interno de los ritmos circadianos bioquímicos, fisiológicos y de comportamiento. Estudios epidemiológicos muestran una relación entre la CD y el aumento en la incidencia de síndrome metabólico, enfermedades cardiovasculares, deterioro cognitivo, trastornos afectivos, alteraciones del sueño, algunos tipos de cáncer y envejecimiento acelerado. La CD puede ser el resultado de alteraciones en los distintos componentes del sistema circadiano (marcapasos central y osciladores periféricos, entradas al reloj, principalmente debidas a defectos de la visión, y salidas del marcapasos y osciladores). La exposición a diferentes sincronizadores (luz, actividad física y social, alimentación) de manera regular robustece el funcionamiento del sistema circadiano mediante la cronopotenciación, que puede atenuar la CD asociada al envejecimiento(AU)

Modern life leads to a more active nocturnal lifestyle, reduced sleep hours and sometimes abrupt shifts across time zones (such as jet lag and shift work) that generate chronodisruption (CD) which can result in premature ageing. CD is defined as a significant disturbance of the internal temporal order of biochemical, physiological and behavioural circadian rhythms. Epidemiological studies show that CD induced by shift work, chronic jet lag, social jet lag and excessive exposure of bright light at night is associated with an increased incidence of metabolic syndrome, cardiovascular disease, cognitive and affective impairment, sleep disorders, some cancers and premature ageing. CD may be the result of disturbances in different components of the circadian system (central pacemaker and peripheral oscillators, inputs to central clock, mainly due to visual deficiencies, and output signals from the pacemaker and oscillators). Exposure to different synchronizers (light, meal times, physical and social activities) with a regular pattern results in a chronoenhacement that can prevent age-related CD(AU)

Age-related changes in mitochondrial membrane composition of rainbow trout (Oncorhynchus mykiss) heart and brain.

Membrane composition, particularly of mitochondria, could be a critical factor by determining the propagation of reactions involved in mitochondrial function during periods of high oxidative stress such as rapid growth and aging. Considering that phospholipids not only contribute to the structural and physical properties of biological membranes, but also participate actively in cell signaling and apoptosis, changes affecting either class or fatty acid compositions could affect phospholipid properties and, thus, alter mitochondrial function and cell viability. In the present study, heart and brain mitochondrial membrane phospholipid compositions were analyzed in rainbow trout during the four first years of life, a period characterized by rapid growth and a sustained high metabolic rate. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and phospholipid class compositions of heart and brain mitochondria, and fatty acid compositions of individual phospholipid classes were determined. Rainbow trout heart and brain mitochondria showed different phospholipid compositions (class and fatty acid), likely related to tissue-specific functions. Furthermore, changes in phospholipid class and fatty acid compositions with age were also tissue-dependent. Heart mitochondria had lower proportions of cardiolipin (CL), phosphatidylserine (PS) and phosphatidylinositol, and higher levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) with age. Heart mitochondrial membranes became more unsaturated with age, with a significative increase of peroxidation index in CL, PS and sphingomyelin (SM). Therefore, heart mitochondria became more susceptible to oxidative damage with age. In contrast, brain mitochondrial PC and PS content decreased in 4-year-old animals while there was an increase in the proportion of SM. The three main phospholipid classes in brain (PC, PE and PS) showed decreased n-3 polyunsaturated fatty acids, docosahexaenoic acid and peroxidation index, which indicate a different response of brain mitochondrial lipids to rapid growth and maturation.

Changes in tissue and mitochondrial membrane composition during rapid growth, maturation and aging in rainbow trout, Oncorhynchus mykiss.

Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging processes, especially during phases of high oxidative stress that result in molecular damage. In the present study, liver and mitochondrial membrane phospholipid (PL) compositions were analyzed in rainbow trout during its four first years of life, a period characterized by rapid growth and high oxidative stress. Specifically, farmed fish of three ages (1-, 2- and 4-years) were studied, and PL compositions of whole liver and liver mitochondria, and fatty acid compositions of individual PL classes were determined. Liver mitochondrial membranes showed a PL composition different to that of the whole tissue suggesting adaptation of cell and subcellular membranes to specific functions. Individual PL had characteristic fatty acid compositions that were similar in whole liver and mitochondrial membranes. Whole liver and mitochondria showed increased lipid peroxidation with age along with changes in membrane PL fatty acid compositions. Most PL classes showed similar changes in fatty acid composition among the age groups, with reduced proportions of docosahexaenoic acid (DHA) and, generally, concomitantly increased levels of monounsaturated fatty acids, which together resulted in reduced peroxidation index (PIn). However, total polyunsaturated fatty acid (PUFA) content did not change significantly with age due to increased eicosapentaenoic acid, docosapentaenoic acid and, in most PL, increased n-6 PUFA. These results suggest there may be oxidation of PL DHA with compensatory mechanisms to maintain membrane fluidity and function. However, modification of fatty acid composition of specific PLs, such as cardiolipin, could affect the electron transport chain efficiency and propagate the oxidative reaction throughout the cell. In addition, both the content and fatty acid composition of sphingomyelin, which has been suggested as a possible mediator of cell dysfunction and apoptosis, changed with age differently to the other PL classes. Moreover, these changes showed different trends between mitochondria and whole liver. These data suggest there is marked oxidative stress associated with rapid growth and maturation in rainbow trout. Changes observed in membrane lipids point to their possible participation in the processes involved in this species response to oxidative stress and damage accumulation rate.

[Chronodisruption and ageing]. / La cronodisrupción como causa de envejecimiento.

Modern life leads to a more active nocturnal lifestyle, reduced sleep hours and sometimes abrupt shifts across time zones (such as jet lag and shift work) that generate chronodisruption (CD) which can result in premature ageing. CD is defined as a significant disturbance of the internal temporal order of biochemical, physiological and behavioural circadian rhythms. Epidemiological studies show that CD induced by shift work, chronic jet lag, social jet lag and excessive exposure of bright light at night is associated with an increased incidence of metabolic syndrome, cardiovascular disease, cognitive and affective impairment, sleep disorders, some cancers and premature ageing. CD may be the result of disturbances in different components of the circadian system (central pacemaker and peripheral oscillators, inputs to central clock, mainly due to visual deficiencies, and output signals from the pacemaker and oscillators). Exposure to different synchronizers (light, meal times, physical and social activities) with a regular pattern results in a chronoenhacement that can prevent age-related CD.