Project description:Curcumin, a yellow pigment extracted from the rhizome of the plant Curcuma longa (turmeric) has been widely used as a spice and herbal medicine in Asia. It has been suggested to have many biological activities such as anti-oxidative, anti-inflammatory, anti-cancer, chemopreventive, and anti-neurodegenerative properties. We evaluated the impact of curcumin on lifespan, fecundity, feeding rate, oxidative stress, locomotion and gene expression in two different wild type Drosophila melanogaster strains, Canton-S and Ives, under two different experimental conditions. We report that curcumin extended the lifespan of two different strains of Drosophila and was accompanied by protection against oxidative stress, improvement in locomotion and chemopreventive effects. Curcumin also modulated the expression of several aging related genes (genes with age-dependent changes in gene expression) such as mth, thor, InR, and JNK. In order to evaluate the impact of curcumin and aging on gene expression, we first determined which genes were affected by aging alone in Canton S flies. Age-related changes in gene expression were defined as changes in expression levels that occurred between 3 and 40 days of age (median lifespan). Among the 18,880 probe sets in the Affymetrix GeneChip® Drosophila Genome 2.0 Array, 1,383 genes (Data on file, 7.3%, P < 0.05) had statistically significant changes in expression levels during this time frame. We next determined the effect of curcumin on gene expression levels in young and aged Canton S flies. Gene expression were defined as changes in expression levels that occurred between 3 and 40 days of aged flies with or without curcumin-feeding.
Project description:Dietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.
Project description:Curcumin, a yellow pigment extracted from the rhizome of the plant Curcuma longa (turmeric) has been widely used as a spice and herbal medicine in Asia. It has been suggested to have many biological activities such as anti-oxidative, anti-inflammatory, anti-cancer, chemopreventive, and anti-neurodegenerative properties. We evaluated the impact of curcumin on lifespan, fecundity, feeding rate, oxidative stress, locomotion and gene expression in two different wild type Drosophila melanogaster strains, Canton-S and Ives, under two different experimental conditions. We report that curcumin extended the lifespan of two different strains of Drosophila and was accompanied by protection against oxidative stress, improvement in locomotion and chemopreventive effects. Curcumin also modulated the expression of several aging related genes (genes with age-dependent changes in gene expression) such as mth, thor, InR, and JNK.
Project description:Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood-brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
Project description:A key challenge in aging research is to extend lifespan in tandem with slowing down functional decline so that the life with good health (healthspan) can be extended. Here, we show that clearance of a small number of cells, which highly express p21Cip1 (p21high), starting from 20 months improves cardiac and metabolic function, and extends both median and maximum lifespan in mice. Importantly, by assessing health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting morbidity compression and healthspan extension. Mechanistically, p21high cells encompass several cell types, with a conserved pro-inflammatory signature. Clearance of p21high cells reduces inflammation, and rejuvenates transcriptomic signatures of various tissues to younger states. These findings demonstrate the feasibility of morbidity compression in mice, and indicate p21high cells as a therapeutic target for healthy aging.
Project description:Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans. Key words: Sirtuins, lifespan, healthspan, osteoporosis, muscle wasting, inflammation
2014-09-22 | GSE49000 | GEO
Project description:dietary genistein modulates homeostasis of the aging gut and extends healthspan and lifespan in aging mammals
Project description:Aging is a major international concern and brings with it formidable socioeconomical and healthcare challenges. An attainable approach to improve general health in humans is using small molecules. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits aging-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in the aging animal model C. elegans, which shares many major longevity pathways with those of mammals. Tomatidine improves behaviors related to healthspan, including increased pharyngeal pumping and swimming movement, and also reduces deterioration of muscle cells in worms. Microarray, imaging, and behavioral analysis reveal that tomatidine maintains mitochondrial homeostasis through mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the cellular antioxidant response SKN-1/Nrf2 pathway, followed by increased mitophagy in worms, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions towards diseases of aging.
Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level.
Project description:Epigenetic remodeling is central to understanding the molecular mechanisms that occur and drive human aging. In fact, DNA methylation clocks are capable of estimating biological age, which determines human lifespan and healthspan. Here, using Illumina's MethylationEPIC array technology, we have profiled the DNA methylation landscape of peripheral whole blood samples from adult individuals ranging in age from 19 to 96 years.