| 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. |
| Discovering lifespan extension drugs by screening for stress resistanceLong-lived organisms tend to be resistant to many types of stress, whereas short-lived organisms tend to be stress sensitive. This allows us to screen for longevity mutants by looking for stress resistance rather than long life. The same logic ought to apply to small-molecule drugs: Any compound that increases stress resistance has an improved change of extending lifespan. That hypothesis has been operationally tested by the Lithgow lab, who performed a small-scale screen of antioxidant compounds and looked for molecules that increased thermotolerance in the worm C. elegans. Several of these drugs also increased lifespan. |
| Anti-aging beer? Engineering yeast to produce resveratrolYeast has taught us a great deal about the mechanisms of aging. But what about using yeast to fight the aging process itself? A group of young scientists is trying to genetically engineer brewer’s yeast to make resveratrol, an antioxidant compound that activates sirtuins and may or may not extend mammalian lifespan. |
| Aging interventions in rodents and humans don't always work the same wayBiogerontologists have learned a lot about the mechanisms of aging by studying "model organisms" -- shorter-lived animals that are experimentally tractable -- and extrapolating those results to humans. This is generally an effective strategy but it doesn't always work. A new study, on the mechanisms of calorie restriction in regulating age-controlling hormones, reminds us that we can't always assume that results obtained in rodent studies will hold true in humans. |
| Klotho: a natural hormone that slows aging and cancerhe soluble protein Klotho was initially widely believed to be an anti-aging factor: knockout mice showed signs of accelerated aging and tumor formation. More recent results have called that into question, suggesting that Klotho mutants mimic progeria without actually undergoing bona fide accelerated aging. The newest study of the protein demonstrates at the molecular level that Klotho inactivates a pro-aging pathway, and also slows the growth of breast cancer. While still controversial, the idea that Klotho is an anti-aging factor is still very much alive. |
| Lifestyle modifications increase telomerase activityA pilot study examined the effect of three months of lifestyle changes on telomerase activity. The authors found that 3 months of “comprehensive lifestyle modifications” resulted in increased telomerase activity in circulating PBMCs of 24 subjects with low-risk prostate cancer. |
| Behavior, gene expression, and biomarkers of physiological ageMost microarray studies of aging animals try to associate gene expression with chronological age: they look for groups of genes that are upregulated or downregulated as we get older. But chronological age is often an imperfect proxy for the quantity we are really interested in – physiological age, or bodily health, which is notoriously difficult to quantify. In the latest issue of Aging Cell, Golden et al. argue that behavior is a useful proxy for physiological age. |
| Assessing the effect of calorie restriction on tumor cellsUsing blood serum derived from human participants in calorie restriction studies, scientists are studying the effects of CR on the growth of cancer cells. Their conclusion: ordinary day-to-day CR has little effect, but alternate-day fasting has a significant beneficial outcome. |
| Cold Spring Harbor aging meeting -- liveblogged by an attendeeAn attendee at the CSHL 2008 meeting on the "Molecular Genetics of Aging" is liveblogging the event. Topics (so far) include senescence, apoptosis, biogerontological experiments in smaller organisms, and telomere studies. The short blog entry linked here has an index of links to all of the sessions. |
| "Exercise pill" target gene may contribute to skin aging and cell deathAMP-activated kinase (AMPK) agonists mimic the effects of exercise, raising the possibility of a “workout pill” that could simulate the effects of vigorous activity. The applications to human health are, to mildly understate the case, significant; it sounds almost too good to be true. That may be the case: AMPK causes cell death in response to ultraviolet light, so activating the gene might exacerbate the photoaging effects of sunlight. |
| Blood cell telomere length can help predict and diagnose vascular diseasePatients with abdominal aortic aneurysms (AAA) had decreased telomere content in their vascular tissues, relative to tissues from subjects free of aortic disease, supporting the link between dysfunctional telomeres and dysfunctional vasculature. A new study demonstrates that the telomeres in their peripheral blood cells reflect this telomere shortening -- which means that the diagnosis can be made with a blood test rather than an aortic biopsy. |
| Slowing aging by boosting autophagyAs they age, cells accumulated damaged molecules that interfere with cellular function; it is therefore important to "take out the trash" via a pathway known as autophagy. Autophagy becomes less efficient with age, causing a vicious cycle in which damage accumulates more and more rapidly. Scientists have now shown that artificially maintaining autophagy at youthful levels can delay age-related decline in cellular function, at least in the liver of mice. |
| A genetic variant linked to human longevityMutations in genes involved in the insulin/IGF-1 signaling pathway (IIS) improve longevity in animal models, but there is minimal evidence that mutations in human homologues of genes in this pathway are associated with a long-lived phenotype. In order to find such evidence, one could take a traditional forward genetics approach and examine populations of centenarians. A new study in elderly Japanese men has done just that -- and has revealed that a common variant in a human homolog of an IIS pathway gene is associated with increased longevity. |
| How premature aging resembles enhanced longevityShort-lived and long-lived mutants exhibit a surprising degree of phenotypic overlap. A series of careful studies of hormone and mRNA levels in these mutants suggest that the common features shared by progeroid and long-lived mutants reflect the body's natural defenses against the aging process. |
| Exercise and calorie restriction: Common mechanisms of longevity promotion?The mitochondrial changes caused by exercise are very similar to the physiological consequences of calorie restriction (CR), an intervention that is known to extend lifespan in model organisms and to delay age-related disease in humans. This fits in nicely with other recent observations connecting exercise and CR. |
| A mitochondrial gene that slows brain agingResearchers have delayed the onset of neurological decline in mice, by introducing a human gene involved in mitochondrial transcription. The paper provides further evidence that oxidative damage is an important causative factor in age-related deterioration of the brain. |
| Inflammation, aging and cancerCentenarians tend to have less robust inflammatory responses. The reduction in inflammatory capacity isn’t large (not even two-fold at the level of primary cytokine output, though quantifying the difference depends ultimately on which endpoint one is measuring), so this gives credence to the idea that tailored anti-inflammatory drugs — perhaps targeted to individual tissues -- could help slow age-related onset of cancers. |
| Telomere dysfunction provides new biomarkers of agingIt would be nice to have access to a biological measurement (or series of measurements) that allowed us to determine an individual’s age. Until we have such a tool, questions like “how rapidly is this individual aging?” are meaningless. A new study identifies a new class of biomarkers: proteins produced by cells with shortened telomeres. |
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