longevity tagged posts

Genetic influence on Aging into the 90s but not beyond

The role of FoxO3 in longevity may involve upregulation of target genes involved in stress resistance, metabolism, cell cycle arrest, and apoptosis. Effective control of FoxO3 in response to environmental stimuli is likely critical to prevent ageing and age-related diseases including cardiovascular disease, type 2 diabetes, cancer and neurodegenerative diseases. The diagram shows how the well-known longevity-associated intervention of caloric restriction helps to maintain the redox state of the cell by cycling calories through the mitochondria so as to restore NAD+. Caloric restriction results in activation of sirtuins, leading to activation of FoxOs, improved autophagy, amino acid recycling via inhibition of mTOR activity, and other mechanisms leading to a healthy ageing phenotype. On the other hand, excess calories, particularly from carbohydrates, increase the NADH/NAD+ ratio and leads to lipogenesis, overproduction of ROS by mitochondria, poor autophagy and activation of mTOR as a result of an excess of protein intake. AKT1 is a term derived from the ‘Ak' mouse strain that develops spontaneous thymic lymphomas (AKT1 is also known as protein kinase B). CAD = Coronary artery disease; HNF4a = hepatocyte nuclear factor 4α; GCN1l1 = general control of amino acid synthesis 1-like 1; O-GlcNAc = O-linked N-acetylglucosamine; OXPHOS = oxidative phosphorylation; PPARγC1α = peroxisome proliferator-activated receptor-γ coactivator 1α; TCA = tricarboxylic acid.

The role of FoxO3 in longevity may involve upregulation of target genes involved in stress resistance, metabolism, cell cycle arrest, and apoptosis. Effective control of FoxO3 in response to environmental stimuli is likely critical to prevent ageing and age-related diseases including cardiovascular disease, type 2 diabetes, cancer and neurodegenerative diseases. The diagram shows how the well-known longevity-associated intervention of caloric restriction helps to maintain the redox state of the cell by cycling calories through the mitochondria so as to restore NAD+. Caloric restriction results in activation of sirtuins, leading to activation of FoxOs, improved autophagy, amino acid recycling via inhibition of mTOR activity, and other mechanisms leading to a healthy ageing phenotype...

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Longevity-promoting Superstar gets revealed in Caenorhabditis Reproducibility Project

(a–c) Dose response effects on the median lifespan of select C. briggsae strains after treatment with chemicals that exhibited strong positive effects on the C. elegans strains. Dosing was performed only on strains that failed to respond positively in the initial tests (single dose experiments), as we did not attempt to identify peak responses, instead we only sought to identify whether positive effects could be obtained by altering doses. Chemical doses were chosen to center around the effective dose identified for C. elegans strains and were sometimes expanded after preliminary rounds of testing. ThT exhibited a positive effect on strain JU1348 at 25 μM, but was profoundly toxic to all strains at and above 100 μM

(a–c) Dose response effects on the median lifespan of select C. briggsae strains after treatment with chemicals that exhibited strong positive effects on the C. elegans strains. Dosing was performed only on strains that failed to respond positively in the initial tests (single dose experiments), as we did not attempt to identify peak responses, instead we only sought to identify whether positive effects could be obtained by altering doses. Chemical doses were chosen to center around the effective dose identified for C. elegans strains and were sometimes expanded after preliminary rounds of testing. ThT exhibited a positive effect on strain JU1348 at 25 μM, but was profoundly toxic to all strains at and above 100 μM

The amyloid dye Thioflavin T emerged as the superstar when age rese...

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Longevity, human Health may be linked to Muscle Cell Enzyme

Schematic overview of the endogenous regulators and molecular targets of SIRT3.

Schematic overview of the endogenous regulators and molecular targets of SIRT3.

Exercise and fasting do not change the location of a key enzyme involved in energy production, a study in Experimental Physiology found. SIRT3 is an important enzyme involved in fat metabolism and energy production. Located within the mitochondria of skeletal muscle, it targets certain proteins and altering their activity.

To determine if SIRT3’s location within muscle cells changes, healthy young men were split into two groups with one being subjected to endurance exercise for an hour and the other fasting for 48 hours. The researchers then took skeletal muscle biopsies at various time points post exercise and fasting and isolated the mitochondria...

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Genetic Switch turned on during Fasting helps stop Inflammation

Salk researchers uncover a fasting molecule, Crtc, which enhances immunity. The gastrointestinal tract of flies lacking Crtc, which is turned on during fasting (right panel), expresses more immune-related molecules compared with those of normal flies (left panel). These signs of inflammation mean that the gut barrier is compromised and more permeable to bacteria. Credit: Salk Institute

Salk researchers uncover a fasting molecule, Crtc, which enhances immunity. The gastrointestinal tract of flies lacking Crtc, which is turned on during fasting (right panel), expresses more immune-related molecules compared with those of normal flies (left panel). These signs of inflammation mean that the gut barrier is compromised and more permeable to bacteria. Credit: Salk Institute

A molecular pathway activated in the brain during fasting helps halt the spread of GI bacteria into the bloodstream, according to a new study researchers at the Salk Institute. A molecular pathway by which the brain communicates with the GIT prevents unnecessary activation of the immune system during fasting by strengthening the barrier against gut microbes...

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