A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans

The study of long-lived C. elegans mutants suggests that mitochondrial oxidants can actually help reduce aging by acting as stress signals, rather than acting solely as toxic molecules

Mclk1+/- mice are not resistant to the development of atherosclerosis

<p>Abstract</p> <p>Background</p> <p>Mice with a single copy of <it>Mclk1 </it>(a.k.a. <it>Coq7</it>), a gene that encodes a mitochondrial enzyme required for the biosynthesis of ubiquinone and other functions, live longer than wild-type mice. The prolonged survival implies a decreased mortality from age-dependent lethal pathologies. Atherosclerosis is one of the main age-dependent pathologies in humans and can be modeled in mice that lack Apolipoprotein E (<it>ApoE</it>^-/-) or mice that lack the Low Density Lipoprotein Receptor (<it>LDLr</it>^-/-) in addition to being fed an atherosclerosis-inducing diet. We sought to determine if <it>Mclk1 </it>heterozygosity protects against atherosclerosis and dyslipidemia in these models.</p> <p>Results</p> <p>We found that <it>Mclk1 </it>heterozygosity did not protect against dyslipidemia, oxidative stress, or atherosclerosis in young (6 or 10 months) or older (18 months) mice. Furthermore, the absence of <it>ApoE </it>suppressed the lifespan-promoting effects of <it>Mclk1 </it>heterozygosity.</p> <p>Conclusion</p> <p>These findings indicate that although <it>Mclk1 </it>heterozygosity can extend lifespan of mice, it does not necessarily protect against atherosclerosis. Moreover, in the presence of hyperlipidemia and chronic inflammation, <it>Mclk1 </it>heterozygosity is incapable of extending lifespan.</p

A Mild Impairment of Mitochondrial Electron Transport Has Sex-Specific Effects on Lifespan and Aging in Mice

Impairments of various aspects of mitochondrial function have been associated with increased lifespan in various model organisms ranging from Caenorhabditis elegans to mice. For example, disruption of the function of the ‘Rieske’ iron-sulfur protein (RISP) of complex III of the mitochondrial electron transport chain can result in increased lifespan in the nematode worm C. elegans. However, the mechanisms by which impaired mitochondrial function affects aging remain under investigation, including whether or not they require decreased electron transport. We have generated knock-in mice with a loss-of-function Risp mutation that is homozygous lethal. However, heterozygotes (Risp+/P224S) were viable and had decreased levels of RISP protein and complex III enzymatic activity. This decrease was sufficient to impair mitochondrial respiration and to decrease overall metabolic rate in males, but not females. These defects did not appear to exert an overtly deleterious effect on the health of the mutants, since young Risp+/P224S mice are outwardly normal, with unaffected performance and fertility. Furthermore, biomarkers of oxidative stress were unaffected in both young and aged animals. Despite this, the average lifespan of male Risp+/P224S mice was shortened and aged Risp+/P224S males showed signs of more rapidly deteriorating health. In spite of these differences, analysis of Gompertz mortality parameters showed that Risp heterozygosity decreased the rate of increase of mortality with age and increased the intrinsic vulnerability to death in both sexes. However, the intrinsic vulnerability was increased more dramatically in males, which resulted in their shortened lifespan. For females, the slower acceleration of age-dependent mortality results in significantly increased survival of Risp+/P224S mice in the second half of lifespan. These results demonstrate that even relatively small perturbations of the mitochondrial electron transport chain can have significant physiological effects in mammals, and that the severity of those effects can be sex-dependent

Efectos de la velocidad de la fase excéntrica y de la carga en el trabajo mecánico en el ejercicio de sentadilla con salto

La fuerza ocupa un lugar esencial para cualquier ser humano, ya sea como capacidad física fundamental, limitante del rendimiento, o bien para garantizar la realización de cualquier acción motora (Siff y Verkhoshansky, 2000). El entrenamiento de fuerza está recomendado por organizaciones nacionales de salud como la American College of Sports Medicine (ACSM) para la mayoría de las poblaciones, incluidos adolescentes, adultos sanos, ancianos y poblaciones clínicas (Garber et al., 2011). Presentar unos niveles adecuados de masa muscular es un aspecto importante desde el punto de vista de la salud, ya que tener un bajo porcentaje de masa muscular está asociado con un mayor riesgo de patologías, como las enfermedades cardiovasculares (Srikanthan et al., 2016), el riesgo cardiometabólico en adolescentes (Burrowset al., 2017), así como diabetes tipo II en adultos de mediana edad y mayores (Son et al., 2017). El entrenamiento de la fuerza es una modalidad de ejercicio que ha crecido en popularidad durante las últimas dos décadas, no solo por su papel en la salud, sino también particularmente por su rol en la mejora del rendimiento atlético al aumentar la fuerza muscular, la potencia y la velocidad, la hipertrofia, la resistencia muscular local, el rendimiento motor, el equilibrio y la coordinación (Kraemer y Ratamess, 2004) Todos estos potenciales beneficios hacen que los programas de fuerza representen una modalidad de entrenamiento importante para los atletas

Valoración de la producción de potencia en ejercicios de fuerza con biofeedback alterado

El presente trabajo final de grado pretende estudiar si afecta el hecho de proporcionar feedback verbal aumentado (positivo o negativo) en la eficiencia y redimiendo del deportista, concretamente en la producción de potencia aguda en el ejercicio de press de banca lanzado con maquina smith. En anteriores estudios se ha podido observar que el feedback aumentado positivo y negativo producen mayor rendimiento que un feedback real o con no proporcionar feedback. A causa de que hay poca evidencia científica al respecto en el entrenamiento de resistencia con cargas, surge nuestra propuesta de intervención. En ésta hubo 14 participantes (hombres) que realizaron dos sesiones de intervención, una primera en la que se estimaba su 1rm, para posteriormente poder llevar a cabo una segunda sesión donde realizaban seis series de seis repeticiones al 50%rm de su 1rm estimado. En la segunda sesión se les proporcionaba tres tipos de feedback (feedback real, aumentado positivo y aumentado negativo) de manera aleatoria en las diferentes series. Nuestra hipótesis era que en aquellas series en las que se daba un feedback aumentado negativo habría un aumento en la producción de potencia aguda respecto al valor aumentado positivo y el real generado por el participant

Run-on of germline apoptosis promotes gonad senescence in C. elegans

Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on the older theory of antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on of processes that in early life promote fitness. Here we apply this idea to investigate the etiology of senescent pathologies in the reproductive system of Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration. Hermaphrodite germ cells frequently undergo “physiological” (non-damage-induced) apoptosis (PA) to provision growing oocytes. Run-on of such PA is a potential cause of age-related gonad degeneration. We document the continuation of germline apoptosis in later life, and report that genetically blocking or increasing PA retards or accelerates degeneration, respectively. In wild-type males, which lack germ line apoptosis, gonad disintegration does not occur. However, mutational induction of PA in males does not lead to gonad disintegration. These results suggest that as germ-cell proliferation rate declines markedly in aging hermaphrodites (but not males), run-on of PA becomes a pathogenic mechanism that promotes gonad degeneration. This illustrates how hyperfunction, or non-adaptive run-on in later life of a process that promotes fitness in early life, can promote atrophic senescent pathology in C. elegans

A quantitative study of adipokinetic hormone of the firebug, Pyrrhocoris apterus

The development of an enzyme-linked immunoassay (ELISA) for the adipokinetic neuropeptide hormone, Pya-AKH, from the firebug Pyrrhocoris apterus L. is described. The ELISA measures as little as 20 fmol of Pya-AKH. Tested against a range of synthetic peptides, the assay has a high sensitivity for peptides containing the C-terminal motif FTPNWamide. The amounts of Pya-AKH in the brain, corpora cardiaca, suboesophageal ganglia, and fused thoracic and abdominal ganglionic mass are very small, with only the corpora cardiaca containing appreciable levels of the hormone (ca. 4 pmol per bug). Preliminary estimates of the persistence of the hormone in the haemolymph are consistent with values determined for AKHs in other insects, and suggest that Pya-AKH has a rapid turnover with a half-life of ca. 18 min. Measurements of circulating titres of AKH in Pyrrhocoris are only possible in the ELISA described here by using pooled samples of haemolymph, and after preliminary clean-up of the haemolymph samples. The titre of Pya-AKH in resting reproductive female Pyrrhocoris is ca. 1 fmol/μl

Functional Requirements for Heparan Sulfate Biosynthesis in Morphogenesis and Nervous System Development in C. elegans

The regulation of cell migration is essential to animal development and physiology. Heparan sulfate proteoglycans shape the interactions of morphogens and guidance cues with their respective receptors to elicit appropriate cellular responses. Heparan sulfate proteoglycans consist of a protein core with attached heparan sulfate glycosaminoglycan chains, which are synthesized by glycosyltransferases of the exostosin (EXT) family. Abnormal HS chain synthesis results in pleiotropic consequences, including abnormal development and tumor formation. In humans, mutations in either of the exostosin genes EXT1 and EXT2 lead to osteosarcomas or multiple exostoses. Complete loss of any of the exostosin glycosyltransferases in mouse, fish, flies and worms leads to drastic morphogenetic defects and embryonic lethality. Here we identify and study previously unavailable viable hypomorphic mutations in the two C. elegans exostosin glycosyltransferases genes, rib-1 and rib-2. These partial loss-of-function mutations lead to a severe reduction of HS levels and result in profound but specific developmental defects, including abnormal cell and axonal migrations. We find that the expression pattern of the HS copolymerase is dynamic during embryonic and larval morphogenesis, and is sustained throughout life in specific cell types, consistent with HSPGs playing both developmental and post-developmental roles. Cell-type specific expression of the HS copolymerase shows that HS elongation is required in both the migrating neuron and neighboring cells to coordinate migration guidance. Our findings provide insights into general principles underlying HSPG function in development

Aging and Death in an Organism That Reproduces by Morphologically Symmetric Division

In macroscopic organisms, aging is often obvious; in single-celled organisms, where there is the greatest potential to identify the molecular mechanisms involved, identifying and quantifying aging is harder. The primary results in this area have come from organisms that share the traits of a visibly asymmetric division and an identifiable juvenile phase. As reproductive aging must require a differential distribution of aged and young components between parent and offspring, it has been postulated that organisms without these traits do not age, thus exhibiting functional immortality. Through automated time-lapse microscopy, we followed repeated cycles of reproduction by individual cells of the model organism Escherichia coli, which reproduces without a juvenile phase and with an apparently symmetric division. We show that the cell that inherits the old pole exhibits a diminished growth rate, decreased offspring production, and an increased incidence of death. We conclude that the two supposedly identical cells produced during cell division are functionally asymmetric; the old pole cell should be considered an aging parent repeatedly producing rejuvenated offspring. These results suggest that no life strategy is immune to the effects of aging, and therefore immortality may be either too costly or mechanistically impossible in natural organisms

Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72833/1/j.1365-313X.2006.03013.x.pd