Personally, I’m just looking forward to the day all service personnel are replaced by ultra friendly, knowledgeable, and attractive robots.

TED talks: Ray Kurzweil on the coming singularity

Here’s the press release:

Vitamin supplements may protect against noise-induced hearing loss

GAINESVILLE, Fla. — Vitamin supplements can prevent hearing loss in laboratory animals, according to two new studies, bringing investigators one step closer to the development of a pill that could stave off noise-induced and perhaps even age-related hearing loss in humans.

The findings will be reported Wednesday at the Association for Research in Otolaryngology’s annual conference in Baltimore by senior author Colleen Le Prell, a researcher at the University of Florida.

The supplements used in the research studies are composed of antioxidants — beta carotene and vitamins C and E — and the mineral magnesium. When administered prior to exposure to loud noise, the supplements prevented both temporary and permanent hearing loss in test animals.

“What is appealing about this vitamin ‘cocktail’ is that previous studies in humans, including those demonstrating successful use of these supplements in protecting eye health, have shown that supplements of these particular vitamins are safe for long-term use,” said Le Prell, an associate professor in the UF College of Public Health and Health Professions’ department of communicative disorders.

About 26 million Americans have noise-induced hearing loss, according to the National Institute on Deafness and Other Communication Disorders, the agency that funded the studies.

In the first study, UF, University of Michigan and OtoMedicine scientists gave guinea pigs the vitamin supplements prior to a four-hour exposure to noise at 110 decibels, similar to levels reached at a loud concert. Researchers assessed the animals’ hearing by measuring sound-evoked neural activity and found that the treatment successfully prevented temporary hearing loss in the animals.

In humans, temporary noise-induced hearing loss, often accompanied by ringing in the ears, typically goes away after a few hours or days as the cells in the inner ear heal. Because repeated temporary hearing loss can lead to permanent hearing loss, the scientists speculate that prevention of temporary changes may ultimately prevent permanent changes.

In the second, related study in mice, UF, Washington University in St. Louis and OtoMedicine researchers showed that the supplements prevented permanent noise-induced hearing loss that occurs after a single loud sound exposure. The researchers found that the supplements prevented cell loss in an inner ear structure called the lateral wall, which is linked to age-related hearing loss, leading the scientists to believe these micronutrients may protect the ear against age-related changes in hearing.

“I am very encouraged by these results that we may be able to find a way to diminish permanent threshold shift with noise exposure,” said Dr. Debara Tucci, an associate professor of surgery in the otolaryngology division at Duke University Medical Center. “I look forward to hearing Dr. Le Prell’s work and reviewing her data.”

The research builds on previous studies that demonstrated hearing loss is not just caused by intense vibrations produced by loud noises that tear the delicate structures of the inner ear, as once thought, said Josef Miller, who has studied the mechanisms of hearing impairment for more than 20 years and is a frequent collaborator of Le Prell’s. Researchers now know noise-induced hearing loss is largely caused by the production of free radicals, which destroy healthy inner ear cells.

“The free radicals literally punch holes in the membrane of the cells,” said Miller, the Townsend professor of communicative disorders at the University of Michigan.

Miller is the co-founder of OtoMedicine, a University of Michigan spinoff company that has patented AuraQuell, the vitamin supplement formula used in the studies.

The antioxidant vitamins prevent hearing damage by “scavenging” the free radicals. Magnesium, which is not a traditional antioxidant, is added to the supplement mix to preserve blood flow to the inner ear and aid in healing.

Antioxidant supplements can also provide “post-noise rescue,” Le Prell said. A previous study by Le Prell and Miller showed that antioxidants can protect hearing days after exposure to loud noise.

“We found that the antioxidant combination of vitamin E and salicylate — the active agent in aspirin –effectively prevented cell death and permanent noise-induced hearing loss even when treatments were delayed up to three days after noise insult,” she said.

The researchers are collaborating on National Institutes of Health-funded clinical trials of the vitamin supplements in college students at UF who wear MP3 music players, and noise-exposed military troops and factory workers in Sweden and Spain.

If the trials show that the vitamins are as effective in preventing noise-induced hearing loss in humans as they have been in animals, Le Prell and Miller envision an easy-to-use supplement that could come in the form of a pill for people headed to a rock concert, a daily supplement for factory workers or a nutritional bar included in soldiers’ rations.

“Ear protection, such as ear plugs, is always the best practice for the prevention of noise-induced hearing loss, but in those populations who don’t or can’t wear hearing protection, for people in which mechanical devices just aren’t enough, and for people who may experience unexpected noise insult, these supplements could provide an opportunity for additional protection,” Le Prell said.

Here’s the link to the article in question: Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1

And the associated press release:

Anti-Aging Pathway Enhances Cell Stress Response

Richard Morimoto EVANSTON, Ill. — People everywhere are feeling the stress of a worldwide recession. Our cells, too, are under continual assault from stress.

Hidden from sight, our cells battle challenges such as their environment, bacteria, viruses, too much or too little oxygen, and physiological stressors. Molecular systems protect cells under assault, but those systems can break down, especially with age.

To better understand how cells are protected from stress and damage, a team led by Northwestern University researchers studied the effect of resveratrol, a beneficial chemical found in red wine, on human cells in tissue culture.

The findings may help explain what happens in neurodegenerative diseases, which are age-related, when cell protection fails, proteins misfold, lots of damage accumulates and the system falls apart.

The researchers discovered a new molecular relationship critical to keeping cells healthy across a long span of time: a protein called SIRT1, important for caloric restriction and lifespan and activated by resveratrol, regulates heat shock factor 1 (HSF1), keeping it active. HSF1 in turn senses the presence of damaged proteins in the cell and elevates the expression of molecular chaperones to keep a cell’s proteins in a folded, functional state. Regulation of this pathway has a direct beneficial effect to cells, the research shows.

This role of SIRT1 — a protein already of great interest to pharmaceutical companies — was not previously known. The results will be published in the Feb. 20 issue of the journal Science.

“When SIRT1 levels are high, you are in a high-protection mode,” said Richard I. Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwestern’s Weinberg College of Arts and Sciences. He led the research team.

“Ironically, triggering the stress response and perhaps maintaining the cell in a protective state over a long period of time can keep cells healthy,” said Morimoto. “The cell is protected against an accumulation of damage when HSF1 is more active.”

SIRT1 levels decrease as humans age, Morimoto explains. Cells can’t respond to stress as well. This decrease in SIRT1 may help explain why protein misfolding diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and adult-onset diabetes, are diseases of aging.

“We now have a powerful way to think about addressing neurodegenerative diseases,” said Morimoto. “We have identified a pathway that can be manipulated to alter lifespan. Discovering this new basis for therapeutics is very exciting.”

The work was supported by the National Institute of General Medical Sciences, the National Institute on Aging and the Rice Institute for Biomedical Research.

In addition to Morimoto, other authors of the Science paper, titled “Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1,” are Sandy D. Westerheide, from Northwestern; Julius Anckar and Lea Sistonen, from Åbo Akademi University in Turku, Finland; and Stanley M. Stevens Jr., from the University of Florida.

The discovery centres around a genetic mutation called Indy (I’m Not Dead Yet) that they first discovered in 2000, which markedly extended (almost doubled) the average lifespans of the flies, with maximum lifespan also seeing a significant, but slightly lower, increase. Here’s their survival graph – impressive!

They’ve now revealed that the mutation causes a reduction in the generation of free radicals as a byproduct of cellular metabolism. Interestingly, this decrease occurred without affecting the energy-production levels in the cell.

By studying the differences in gene expression between the normal and Indy flies over the course of their lifetimes, the researchers found that genes in the oxidative phosphorylation pathway were significantly lower in the Indy flies, with differences becoming increasingly marked as the flies aged.

The researchers believe that the Indy mutants make up for what ought to be a reduced energy-production capacity by increasing their mitochondrial density. This alteration in the mitochondrial physiology may be increasing the cells efficiency, producing more energy relative to ROS (reactive oxygen species) generation.

It’s hoped that these discoveries will one day lead to non-genetic therapeutic interventions that accomplish similar to what’s going on in the Indy mutant fruit flies.

The full text of the article is available here (PDF, open access).

The Life Extension Foundation has put together an excellent rebuttal that provides a concise rundown on the problems with these studies, and it’s worth a read:

Preliminary Rebuttal to Recent Attacks Against Dietary Supplements

By William Faloon

The media recently ran headline news stories claiming that vitamins C, D and E do not prevent heart attack, stroke or breast cancer. This report represents Life Extension’s preliminary response to these media attacks that are based on egregiously flawed studies. We will submit this report for formal peer review and referencing and expect to post our official report within a few weeks.

Needless to say, when these biased attacks are launched, we are not given prior notice so that our side of the story makes it into the mass media.

In the early 1990s, several large population studies showed significant reductions in cardiovascular disease in those who consumed vitamin C or vitamin E.

The most widely reported study emanated from UCLA, where it was announced that men who took 800 mg a day of vitamin C lived six years longer than those who consumed the recommended daily allowance of 60 mg a day. The study, which evaluated 11,348 participants over a 10-year period of time, showed that higher vitamin C intake reduced cardiovascular disease mortality by 42%.

These kinds of findings did not go unnoticed by the federal government, who subsequently invested hundreds of millions of dollars in an attempt to ascertain if relatively modest vitamin doses could prevent common age-related diseases.

In a study that received extensive media coverage, four groups of male doctors were given various combinations of vitamin C and/or vitamin E or placebo. After eight years, there was no reported difference in heart attack or stroke incidence among the groups. This led the media to state that consumers should not buy these supplements.

As you will read, there were so many egregious flaws in this study that the findings are rendered meaningless. Regrettably, consumers who trust their lives to the mainstream media may fall victim to this latest charade to discredit validated methods to reduce cardiovascular disease risk….<snip>

…Read more at LEF’s news page

Apologies for the lack of activity here for the past few weeks – holiday celebrations and associated chores have prevented me from making any updates. Don’t worry – I haven’t missed anything and I’ll be including all the interesting stuff that’s happened over this period, as soon as I get my act together.

Stay tuned!

The other study that came to mind (I can’t find the article, sorry!) was one that found that coffee combined with exercise somehow mitigated the damage caused by sunburn by enhancing apoptosis of damaged cells.

This latest study looks at caffeic acid, a component of coffee, and its ability to inhibit COX-2 release following UV-B exposure:

Caffeic Acid, a Phenolic Phytochemical in Coffee, directly inhibits Fyn Kinase Activity and UVB-induced COX-2 Expression.

Carcinogenesis. 2008 Dec 10; PMID: 19073879

Kang NJ, Lee KW, Shin BJ, Jung SK, Hwang MK, Bode AM, Heo YS, Lee HJ, Dong Z.

Hormel Institute, University of Minnesota, 801 16 Avenue NE, Austin MN, USA.

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in many foods, including coffee. Recent studies suggested that caffeic acid exerts anticarcinogenic effects, but little is known about the underlying molecular mechanisms and specific target proteins. In this study, we found that Fyn, one of the members of the nonreceptor protein tyrosine kinase family, was required for UVB-induced COX-2 expression, and caffeic acid suppressed UVB-induced skin carcinogenesis by directly inhibiting Fyn kinase activity. Caffeic acid more effectively suppressed UVB-induced COX-2 expression and subsequent prostaglandin E(2) (PGE(2)) production in JB6 P+ mouse skin epidermal (JB6 P+) cells compared to chlorogenic acid (5-O-cafeoylquinic acid), an ester of caffeic acid with quinic acid. Data also revealed that caffeic acid more effectively induced the down-regulation of COX-2 expression at the transcriptional level mediated through the inhibition of activator protein (AP)-1 and nuclear factor (NF)-kappaB transcription activity compared to chlorogenic acid. Fyn kinase activity was suppressed more effectively by caffeic acid than by chlorogenic acid, and downstream mitogen-activated protein (MAP) kinases were subsequently blocked. Pharmacological Fyn kinase inhibitor (PP2 and leflunomide) data also revealed that Fyn is involved in UVB-induced COX-2 expression mediated through the phosphorylation of MAP kinases in JB6 P+ cells. Pull-down assays revealed that caffeic acid directly bound with Fyn and noncompetitively with ATP. In vivo data from mouse skin also supported the idea that caffeic acid suppressed UVB-induced COX-2 expression by blocking Fyn kinase activity. These results suggested that this compound could act as a potent chemopreventive against skin cancer.

Most of us experience weight gain over winter, and I had always assumed that it was due to the changes in lifestyle that the winter months necessitate. Physical activity is curtailed because of bad weather; gymming is often eschewed in favor of curling up at home; and heavy, energy-dense food somehow becomes incredibly appetizing. In the northern hemisphere, winter also brings holiday celebrations and wanton feasting.

Certainly, these factors contribute to the winter bulge, but the new idea presented by Dr. Y.J. Foss is that winter weight-gain is an actual physiological, adaptive response by the body to the hardships of winter, and that it’s controlled by the body’s vitamin D status.

Although most people tend to think that the cause of obesity has solely to do with the consumption of excess food and a lack of exercise, there are still factors that defy explanation.

For example, if we assume that the cause of obesity is a mismatch between genes and environment – i.e., some people have a ‘thrifty’ genotype, one that prefers to conserve energy, and they live in the modern western world, where there is an overabundance of food and little need for physical activity, it remains unknown why there is such a difference between different individuals in the same environment. However, if we invoke genetic differences between people as the explanation for individual differences, there is no explanation for why the initiation of weight gain occurs at different points in the course of a person’s life, nor is there an explanation for large-scale trends towards weight gain depending on geographical location, industrialization, and other societal differences.

Also, it remains that most interventions that focus on altering the lifestyle of the overweight individual fail in the long term, which suggests the existence of an as-yet-unexplained causative factor for weight gain.

Therefore, the hypothesis that vitamin D deficiency might be the missing link has been presented.

The body has a seasonal cycle that tends to favor energy storage during the cold, winter months. This ‘winter response’ is thought to be controlled by the levels of circulating vitamin D, which is synthesized by the skin in response to UV light.

So think about it:

• Even fat people usually don’t tend to constantly increase in weight – even though they experienced weight gain, there is some kind of brain-controlled mechanism that keeps their weight stable, even if excessive
• Animals also have a tendency to be larger in cooler climates, indicating weight-gain is a controlled, adaptive response to the environment
• What we consider to be ‘metabolic syndrome’ is actually very similar, if not identical, to the “winter metabolism”

So, it now remains to be tested whether obese individuals have lower plasma calcidiol levels (the form of vitamin D that fluctuates most according to exposure to sunlight). It’s a very exciting theory, because vitamin D deficiency has the potential to explain both large scale trends and individual variation with regard to obesity. It can be inferred that on a population-wide scale, vitamin D status has fallen in line with the increase in obesity – both obesity and low vitamin D status are both artifacts of the urban-industrial lifestyle. Whether the two are linked will be investigated in future study.

One wonders if our friend in the picture above would do well to make a habit of what he’s currently doing.

Reference: Foss YJ, Vitamin D de?ciency is the cause of common obesity, Med Hypotheses (2008), doi:10.1016/j.mehy.2008.10.005
Photo credit: Kyle May on Flickr

Researchers at the Harvard Medical School will be publishing details in the November 28 edition of Cell of a potential mechanism of aging that is conserved throughout the animal kingdom, from yeast to humans.

Professor David Sinclair and his team have discovered that aging may in fact be a case of gene regulation gone haywire, as our cells progressively lose their ability to maintain accurate gene expression patterns.

What this means is, while every cell in our body could potentially express genes from any other cell in our body; e.g., a retina cell could start behaving like a kidney cell, it doesn’t because tissue patterns of gene expression are kept under tight control. And well they should – a lot of damage would result if our brain started releasing digestive enzymes.

However, as we age, cells lose this ability and start behaving in a sloppy and erratic way – a lot like old people themselves! These haplessly activated genes are directly linked with the characteristics of aging.

Under normal conditions, sirtuins (those enzymes activated by resveratrol and caloric restriction) police the situation, making sure that the extraneous DNA that is supposed to remain silent and wrapped up actually does so. However, sirtuins have a dual role – when DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.

During this period of distraction, the epigenetic packaging of the genome starts to come apart and the wrong genes start to be expressed. The more DNA damage and free radical activity that occurs (especially due to age-related mitochondrial decay), the more time the sirtuins are deployed elsewhere, and the more time the cell spends doing the wrong, harmful thing.

So, intuitively the solution would be to increase sirtuin number/activity, and this is what CR dieters and resveratrol supplementers are attempting. Sirtuin-overexpressing mice (either as a result of germ-line genetic alteration or resveratrol supplementation) saw a mean lifespan increase of 24-46 percent.

This also lends weight to anti-free radical therapies and mitochondria-preserving therapies (e.g. ALCAR+r-ALA supplementation) as relevant adjuvants to sirtuin stimulation.

This proof-of-concept sure has me hankering for the 2nd generation sirtuin enhancers like SRT-1720 set to hit the markets in the next couple of years. In the meantime, it’s really some excellent food for thought. Could this actually be the root cause of aging in all organisms?

Adapted from a Eurekalert! press release. Photo credit: Cliff1066/flickr

Levels of LDL in the blood depend on a baffling variety of factors; however, a key mechanism involves the LDLR receptor, which controls the elimination of LDLs. These receptors are degraded by what is called ‘PCSK9 proprotein convertase’. So, it stands to reason that the more PCSK9 you have, the fewer LDLR receptors you have, and the more LDL will be floating around causing havoc.

The discovery of the team of Dr. Nabil G. Seidah was that annexin A2 binds strongly to PCSK9, inhibiting its function. This might pave the way to a drug that can lower ‘bad cholesterol’ levels in the same way.

People with naturally inactive PCSK9 have have been shown to have an 88% diminished chance of developing cardiovascular diseases.

Currently, statins are the go-to drug when it comes to lowering LDL levels; however, they are of limited use because they increase the production of PCSK9, thereby creating a tolerance effect. A new drug based on this research could therefore even work in conjunction with statins to improve their effectiveness.

Background

First of all, let me point out that there is no such thing as ‘bad cholesterol’ – there is only one kind of cholesterol, and whether it is ‘good’ or ‘bad’ depends on how and where it is being transported in the body. Cholesterol is vital to life, being necessary to help emulsify fats so they can be transported in the blood. In fact, the concentration of cholesterol stays relatively constant in your body – if you don’t have enough, you body will synthesize more.

Among the various cholesterol packaging and transport modalities, LDL is considered to be ‘bad’ because it is able to transport fat and cholesterol to the arteries, which can lead to atherosclerosis. ‘Good’ cholesterol refers to High Density Lipoproteins (HDLs), and it is believed that HDLs actually do the exact opposite – remove fat and cholesterol deposits from the arteries.

Fortunately, you can increase you HDL levels through lifestyle changes, in particular:

• Performing aerobic exercise
• Losing weight
• Stopping smoking
• Minimizing the amount of trans-fatty acids in the diet (margarine, shortening)
• Consuming alcohol in moderation (1-2 drinks/day)
• Increasing dietary monounsaturated fat intake (canola oil, avocado oil, olive oil, peanut oil)
• Increasing dietary soluble fibre intake (your typical list of healthy food – cereals, legumes, veges, etc.)
• Supplementing with omega 3 fatty acids (fish oil)
• Supplementing with carnitine