| A drug that extends lifespan but shortens healthspan?One of the central precepts of biogerontology is that meaningful lifespan extension will be concomitant with extension of the “healthspan”, i.e., the vigorous part of life — life that is, for lack of a better phrase, worth living. Because of the importance of this assumption, we need to be on the lookout for counterexamples, such as the one provided by a recent study. |
| A transcriptional "switch" that controls the longevity vs. reproduction decisionThe insulin-like growth factor (IGF) pathway is one of the longest-known and well-studied regulators of longevity. Activation of these upstream kinases results in inactivation of the longevity assurance gene DAF-16, which encodes a transcription factor that activates stress resistance genes. A new study demonstrates that DAF-16 also downregulates transcription of the upstream kinases, reinforcing the decision to devote resources to maintenance and repair instead of reproduction. |
| Delaying aging by inhibiting mitochondrial respirationThe CLK-1 ("clock") pathway is a major conserved regulator of longevity: in organisms as diverse as mice and worms, mutations in the CLK-1 gene delay development and extend the lifespan. A new study from the Kenyon lab demonstrates that CLK-1 mutations act by inhibiting mitochondrial respiration, probably by blocking the producing of the essential mitochondrial cofactor ubiquinone (coenzyme Q). |
| Data mining to reveal patterns in age-dependent gene expressionMining collections of dozens or even hundreds of gene expression datasets to identify global trends is becoming increasingly popular, especially in cancer research. But for aging – an area where the data are noisier, and there is perhaps an even stronger need for integrative computational approaches – few studies have compared more than a handful of expression datasets at once, and none in mammals. This is the first rigorous, large-scale integration of mammalian aging microarray data. |
| Why increased donor age decreases transplant efficiencyTissue from older donors is less efficacious in transplants: the older grafts tend not to take as efficiently, and are more likely to be rejected. A new study demonstrates that an increase in cellular senescence may be the culprit. |
| Optimism, pessimism, and telomere length.Is that glass half-empty, or half-full? Be careful - your answer may result in telomere shortening. Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6 in post-menopausal women. |
| Calorie restriction delays immune system aging.Calorie restriction (CR) diets have been shown to increase the health and lifespan of many model animals. Specifically, in short lived rodent models, these beneficial effects have improved immune system function by enhancing immune competence, inhibiting age-related dysregulation of cytokine secretion, and by preventing the accumulation of senescent T cells through increasing apoptosis. |
| Telomerase RNA alone can extend cellular lifespan - but is there a tradeoff?Mounting evidence now indicates that impaired telomerase activity impacts the stem/progenitor compartment, resulting in premature exhaustion of the haemopoietic progenitors, and reduced number of peripheral blood progenitor cells. Mutations in the various subunits of the telomerase complex have been reported, with the RNA subunit, TERC, shown to be the limiting factor for telomerase activity and telomere length in dyskeratosis congenia patient fibroblast strains. |
| Calorie restriction speeds cellular "recycling" of mitochondriaMitochondria are central to many theories of aging because they produce damaging reactive oxygen species (ROS) as a by-product of normal function. Over time, ROS can degrade mitochondrial DNA (mtDNA), interfering with cellular energy production. The cell’s strategy for dealing with this damage is to recycle its mitochondria on a regular basis. A new study shows that calorie restriction increases the rate at which this recycling takes place. |
| Telomeres, the "aging clock", start shortening immediately after birthWhile stem cells exhibit the capacity to differentiate and self- renew, their ability to do so is now known to decline with age. At the level of individual cells, replicative capacity is to reason that telomere dynamics should be intimately involved with this age-related decline in stem cell function. To this end, a recent study has investigated telomere dynamics in a longitudinal study of fetal and early post-natal subjects. |
| Calorie restriction prevents age-related damage to mitochondriaA new study has measured the number of abasic sites (AP, referring to apurinic and apyrimidinic) in the mitochondrial genome of young and aged rat brain. AP sites are positions along the DNA backbone where no adenine, guanine, cytosine, or thymine is attached; they are among the most frequent damages to DNA. The authors showed that in normally feeding animals, the number of AP sites increases with age — but calorie restricted (CR) mice did not show such an increase. |
| Telomerase overexpression slows agingExpressing telomerase in a wide variety of somatic cells would seem a tempting strategy for lifespan extension. Specifically, telomerase expression could prevent any age-related decline in tissue function can be attributed to decreased regenerative potential. We know why this is a non-starter, of course: What do you call a cell with an unlimited division potential that’s not a stem cell or germ cell? Usually “cancer.” But what if cancer couldn’t form for other reasons? |
| Comparing calorie restriction for weight loss vs. CR for longevityAs we know, a calorie restriction (CR) diet improves the health and lifespan in animal models. In the ongoing search for human biomarkers to assess the effects of CR in humans, Crujeiras et al. analyzed sirtuin gene expression changes and blood antioxidant markers in obese patients who followed a 30% calorie restricted diet for 8 weeks. Overall, patients had a significant reduction in body weight, BMI, fat mass and cholesterol but showed no significant changes in glucose, triglycerides, insulin or insulin resistance (It’s possible that if these patients had maintained a CR diet for a longer period of time, significant changes would have been noted.) Total antioxidant capacity (AOP) and nitric oxide levels were significantly increased, and glutathione peroxidase was significantly decreased, indicating an improvement in the oxidative stress response. |
| Sex and the aging brain: gender differences in neurodegeneration and brain agingA recent study of aging in four areas of the human brain is the first to look at gender differences in brain aging. The study revealed substantial sexual dimorphism in gene expression changes over the course of the aging process -- perhaps explaining why men and women undergo age-related change and neurodegeneration at different times and in different ways. |
| An anti-neurodegeneration drug might act by delaying the aging process itselfScientists have characterized the wide-spectrum anti-neurodegeneration drug cliquinol, and discovered that it downregulates the activity of the CLK-1 enzyme, a protein involved in regulation of lifespan. The authors argue that direct enzymatic inhibition of the pathway might be preventing neurodegeneration primarily by slowing down the aging process. |
| Mitochondrial uncouplers mimic the effects of calorie restrictionUncouplers are compounds that break the circuit between mitochondrial respiration and production of ATP. When mice were treated with these compounds, they had higher rates of respiration with lower production of ROS. These mice also had lower oxidative damage to their DNA and proteins, another hallmark of calorie restriction. They showed lowered blood glucose, lower triglycerides, and lower insulin. Most importantly, DNP treated mice showed an extended lifespan. |
| The role of miRNAs in aging skeletal muscleMicroRNAs (miRNAs) are short RNA molecules that function as negative regulators of protein translation and participate in a variety of cellular processes such as development and disease. Data from experiments analyzing the role of miRNA gene regulation in aging pathways have been variable, so the precise role of miRNAs in aging systems remains to be determined. A recent study shows the effect of exercise and aging on miRNA expression, and asks questions about the functional relevance of these small regulatory RNAs. |
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