Longevity in mice: is stress resistance a common factor?

A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, α-MUPA knockout, p66shc knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan

The Value of Daily Money Management: An Analysis of Outcomes and Costs

10.1080/15433714.2011.581530Journal of Evidence-Based Social Work95498-51

The Anisotropic Yield Surface of Cellular Materials

Mechanical metamaterials are often limited in engineering applications because of uncertainty in their deformation behavior. This uncertainty necessitates large factors of safety and behavior assumptions to be included in mechanical metamaterial designs, detracting from the largest benefit of metamaterials: their ultralight weight. In this study, a yield envelope was created for both a bending dominated and a stretching dominated cellular material topology to improve the understanding of the response of cellular materials under various load types and orientations. Experimental studies revealed that the shear strength of a cellular material is significantly less than that predicted by the Mohr’s criterion, necessitating a modification of the Mohr’s yield criterion for cellular materials. Both topologies experienced tension-compression anisotropy and anisotropy dependent on the topology orientation during loading with the stretching dominated topology experiencing the largest anisotropies.Mechanical Engineerin

Statement by the Growth Hormone Research Society on the GH/IGF-I Axis in extending health span

Despite the fact that growth hormone (GH) has not been approved for antiaging purposes, its use for this indication is widespread and increasing. The Growth Hormone Research Society (GRS) convened an international workshop to critically review and debate the available evidence related to the use of GH in the older adults and the relationship between the GH/insulin-like growth factor I (IGF-I) axis and the aging process. This statement presents the conclusions reached and gives recommendations for future studies in this research field regarding the use of GH and growth hormone secretagogues (GHS) for promoting health span. The participants concluded that, until future clinical research in this area is conducted, in particular carefully designed, long-term studies, using validated outcome parameters, the clinical use of GH or GHS in older adults, alone or in combination with testosterone, cannot be recommended. In addition, future basic studies in model systems, to continue to unravel GH/IGF-I effects related to human life span and health span, were advocated.Michael O. Thorner ... Ian Chapman ... [et al.

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes

Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage

Insulin receptor substrate-1 null (Irs1 −/−) mice are long lived and importantly they also demonstrate increased resistance to several age-related pathologies compared to wild type (WT) controls. Currently, the molecular mechanisms that underlie lifespan extension in long-lived mice are unclear although protection against oxidative damage may be important. Here, we determined both the activities of several intracellular antioxidants and levels of oxidative damage in brain, skeletal muscle, and liver of Irs1 −/− and WT mice at 80, 450, and 700 days of age, predicting that long-lived Irs1 −/− mice would be protected against oxidative damage. We measured activities of both intracellular superoxide dismutases (SOD); cytosolic (CuZnSOD) and mitochondrial (MnSOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase (CAT), and reduced glutathione (GHS). Of these, only hepatic CAT was significantly altered (increased) in Irs1 −/− mice. In addition, the levels of protein oxidation (protein carbonyl content) and lipid peroxidation (4-hydroxynonenal) were unaltered in Irs1 −/− mice, although the hepatic GSH/GSSG ratio, indicating an oxidized environment, was significantly lower in long-lived Irs1 −/− mice. Overall, our results do not support the premise that lifespan extension in Irs1 −/− mice is associated with greater tissue antioxidant protection or reduced oxidative damage