Dear reader(s),

I realize the update schedule of this blog has been on a downward trajectory in recent months, which is perhaps due to a slowdown in the rate of scientific advances in the field of anti-aging, or maybe my threshold for what I feel is important or interesting has increased.

Regardless, on reflection it’s become clear that there are in fact some interesting and cool ways that one could meaningfully contribute to the transhumanist agenda, but this blog in its current form doesn’t really do that apart from acting as a kind of news filter for those who don’t have time to trawl through the hundreds of abstracts and press releases published daily that relate tangentially to this field.

With that in mind, I am currently in the process of creating a new and improved FlyingHigh.org, offering some really useful and interesting functionality that will hopefully prove useful to everyone out there who, like me, wishes to burn brightly in perpetuity.

It might take a while, so by all means go ahead and sign up for the RSS feed or email alerts, and I’ll invite you all back when it’s ready to go!

This article, which appeared the other day in the Journal of Nutrition shows that high-dose CoQ10 impaired cognitive function in mice and had no effect on increasing life-span. One wonders if idebenone suffers the same drawbacks.

Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice.

J Nutr. 2009 Aug 26.

Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJ.

Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107.

Coenzyme Q(10) (CoQ(10)) is widely consumed as a dietary supplement to enhance bioenergetic capacity and to ameliorate the debilitative effects of the aging process or certain pathological conditions. Our main purpose in this study was to determine whether CoQ(10) intake does indeed attenuate the age-associated losses in motor, sensory, and cognitive functions or decrease the rate of mortality in mice. Mice were fed a control nonpurified diet or that diet containing 0.68 mg/g (low dosage) or 2.6 mg/g (high dosage) CoQ(10), starting at 4 mo of age, and were tested for sensory, motor, and cognitive function at 7, 15, and 25 mo of age. Amounts of the ubiquinols CoQ(9)H(2) and CoQ(10)H (2) measured in a parallel study were augmented in the cerebral cortex but not in any other region of the brain. Intake of the low-CoQ(10) diet did not affect age-associated decrements in muscle strength, balance, coordinated running, or learning/memory, whereas intake at the higher amount increased spontaneous activity, worsened the age- related losses in acuity to auditory and shock stimuli, and impaired the spatial learning/memory of old mice. The CoQ(10) diets did not affect survivorship of mice through 25 mo of age. Our results suggest that prolonged intake of CoQ(10) in low amounts has no discernable impact on cognitive and motor functions whereas intake at higher amounts exacerbates cognitive and sensory impairments encountered in old mice. These findings do not support the notion that CoQ(10) is a fitness-enhancing or an “antiaging” substance under normal physiological conditions.

Early research findings may lead to new treatments for the disease

UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer’s disease.

The early research findings, which appear in the July issue of the Journal of Alzheimer’s Disease, may lead to new approaches in preventing and treating Alzheimer’s by utilizing the property of vitamin D3 — a form of vitamin D — both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta.

Vitamin D3 is an essential nutrient for bone and immune system health; its main source is sunshine, and it is synthesized through the skin. Deficiencies may occur during winter months or in those who spend a lot of time indoors, such as Alzheimer’s patients.

“We hope that vitamin D3 and curcumin, both naturally occurring nutrients, may offer new preventive and treatment possibilities for Alzheimer’s disease,” said Dr. Milan Fiala, study author and a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

Using blood samples from nine Alzheimer’s patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages that act as the immune system’s clean-up crew, traveling through the brain and body and gobbling up waste products, including amyloid beta. Researchers incubated the macrophages with amyloid beta, vitamin D3 and natural or synthetic curcumin.

The synthetic curcuminoid compounds were developed in the laboratory of John Cashman at the Human BioMolecular Research Institute, (http://www.hbri.org/), a nonprofit institute dedicated to research on diseases of the human brain.Researchers found that naturally occurring curcumin was not readily absorbed, that it tended to break down quickly before it could be utilized and that its potency level was low, making it less effective than the new synthetic curcuminoids.

“We think some of the novel synthetic compounds will get around the shortcomings of curcumin and improve the therapeutic efficacy,” Cashman said.

The team discovered that curcuminoids enhanced the surface binding of amyloid beta to macrophages and that vitamin D strongly stimulated the uptake and absorption of amyloid beta in macrophages in a majority of patients.

Previous research by the team demonstrated that the immune genes MGAT III and TLR-3 are associated with the immune system’s ability to better ingest amyloid beta. In this earlier work, Fiala noted, it was shown that there are two types of Alzheimer’s patients: Type 1 patients, who respond positively to curcuminoids, and Type II patients, who do not.

“Since vitamin D and curcumin work differently with the immune system, we may find that a combination of the two or each used alone may be more effective — depending on the individual patient,” he said.

Fiala noted that this is early laboratory research and that no dosage of vitamin D or curcumin can be recommended at this point. Larger vitamin D and curcumin studies with more patients are planned.

Read more here…

In this study, senescent-prone rats were subjected to melatonin between 1 and 10 months of age and their brains investigated for signs of mitochondrial aging. The very promising result for those currently supplementing or planning to supplement with melatonin was that Melatonin administration between 1 and 10 months of age completely prevented the mitochondrial impairment, maintaining or even increasing ATP production.

Viz:

Long-term melatonin administration protects brain mitochondria from aging

J Pineal Res. 2009 Jul 1.

We tested whether chronic melatonin administration in the drinking water would reduce the brain mitochondrial impairment that accompanies aging. Brain mitochondria from male and female senescent prone (SAMP8) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation and nitrite, glutathione/glutathione disulfide ratio, and glutathione peroxidase and glutathione reductase activities. Electron transport chain activity and oxidative phosphorylation capability of mitochondria were also determined by measuring the activity of the respiratory chain complexes and the ATP content. The results support a significant age-dependent mitochondrial dysfunction with a diminished efficiency of the electron transport chain and reduced ATP production, accompanied by an increased oxidative/nitrosative stress. Melatonin administration between 1 and 10 months of age completely prevented the mitochondrial impairment, maintaining or even increasing ATP production. There were no major age-dependent differences between males in females, although female mice seemed to be somewhat more sensitive to melatonin treatment than males. Thus, melatonin administration as a single therapy maintained fully functioning brain mitochondria during aging, a finding with important consequences in the pathophysiology of brain aging.

Authors: Carretero M, Escames G, López LC, Venegas C, Dayoub JC, García L, Acuña-Castroviejo D. Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada and RETICEF, Granada, Spain.

A new article in the FASEB Journal shows that resistance to protein folding damage is a clue to longevity in mammals.

Scientists from Texas are batty over a new discovery which could lead to the single most important medical breakthrough in human history—significantly longer lifespans. The discovery, featured on the cover of the July 2009 print issue of The FASEB Journal, shows that proper protein folding over time in long-lived bats explains why they live significantly longer than other mammals of comparable size, such as mice.

“Ultimately we are trying to discover what underlying mechanisms allow for some animal species to live a very long time with the hope that we might be able to develop therapies that allow people to age more slowly,” said Asish Chaudhuri, Professor of Biochemistry, VA Medical Center, San Antonio, Texas and the senior researcher involved in the work.

Asish and colleagues made their discovery by extracting proteins from the livers of two long-lived bat species (Tadarida brasiliensis and Myotis velifer) and young adult mice and exposed them to chemicals known to cause protein misfolding. After examining the proteins, the scientists found that the bat proteins exhibited less damage than those of the mice, indicating that bats have a mechanism for maintaining proper structure under extreme stress.

“Maybe Juan Ponce De León wasn’t too far off the mark when he searched Florida for the Fountain of Youth,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “As it turns out, one of these bat species lives out its long life in Florida. Since bats are rodents with wings, this chemical clue as to why bats beat out mice in the aging game should point scientists to the source of this elusive fountain.”

(Journal reference: Salmon et al. The long lifespan of two bat species is correlated with resistance to protein oxidation and enhanced protein homeostasis. The FASEB Journal, 2009; 23 (7): 2317 DOI: 10.1096/fj.08-122523)

Salk Institute researchers have identified an enzyme crucial to the life-extension effects brought about by dietary restriction. This brings us closer to identifying the initiating signal for the cascade of effects organisms experience when subject to CR conditions. Once this ‘holy grail’ is discovered, we’ll be well on the path to creating a drug that activates the cascade.

The article: Climbing the ladder to longevity: critical enzyme pair identified

According to this press release, applying a fluorouracil-containing cream to the skin results in the reduction of the signs of aging. It works essentially by causing superficial damage, which the body then reacts to, healing wrinkles and age spots in the process. The mechanism seems to be similar to that of laser resurfacing.

Topical application of chemotherapy drug may improve appearance of aging skin

Topical application of the chemotherapy medication fluorouracil appears to reduce potentially precancerous skin patches and improve the appearance of sun-damaged skin, according to a report in the June issue of Archives of Dermatology, one of the JAMA/Archives journals.

Fluorouracil stops the body from synthesizing thymine, a building block of DNA, according to background information in the article. This drug is used to treat cancers of the colon, head and neck, pancreas and other organs. In early studies of patients with cancer undergoing treatment with systemic fluorouracil, clinicians noticed changes in skin appearance, which led to the development of a topical therapy for the treatment of actinic keratoses (skin lesions that may develop into skin cancer).

Dana L. Sachs, M.D., of the University of Michigan Medical School, Ann Arbor, and colleagues evaluated molecular and clinical changes in the skin of 21 healthy volunteers with actinic keratoses and sun-damaged skin. Participants applied 5 percent fluorouracil cream to the face twice daily for two weeks; skin biopsies and clinical evaluations were performed at the beginning of the study and periodically throughout treatment. Photographs were also taken at the beginning of the study and after one, two, four, six, 10 and 24 weeks, and were evaluated by three dermatologists who were not involved in examining the patients during the study. Nineteen patients completed all aspects of the study, and 20 responded to a questionnaire at week 10.

The number of actinic keratoses was significantly reduced following treatment, from an average of 11.6 lesions to an average of 1.5. Clinical evaluations also identified overall improvements in aging-related damage, including decreases in fine (small) and course (large) wrinkling, lentigines (dark skin spots), hyperpigmentation (skin that has become darker) and sallowness (a yellow skin tone).

One day after the final fluorouracil treatment, testing of the skin biopsies revealed an increase in the levels of compounds related to skin injury, inflammation and degradation of the extracellular matrix (the non-living tissue that supports skin), in addition to the precursor of collagen, which rebuilds damaged skin. “Topical fluorouracil causes epidermal [outer skin layer] injury, which stimulates wound healing and dermal remodeling resulting in improved appearance,” the authors write. “The mechanism of topical fluorouracil in photo-aged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photo-aging.”

The treatment was generally well tolerated. On the 10-week questionnaire, most patients rated their skin as improved (19, or 95 percent) and were willing to undergo the therapy again (17, or 89 percent).

“For patients in whom a course of topical fluorouracil is indicated for the treatment of actinic keratoses, there will likely be the additional benefit of a restorative effect from sun damage; this may provide further motivation for these patients to undergo the rigorous treatment,” the authors conclude. “It is possible that for some patients topical fluorouracil may have an important role against photo-aging. For others, however, it may not be cosmetically acceptable given that a standard course of therapy may last two to three weeks and the ensuing reaction can persist for several more weeks. Undoubtedly, there will be patients who desire a therapy such as topical fluorouracil for cosmetic purposes given the relatively low cost of this therapy compared with ablative laser resurfacing.”

(Arch Dermatol. 2009;145[6]:659-666. Available pre-embargo to the media at www.jamamedia.org.)

Blocking a muscle growth-limiting hormone protects against obesity and atherosclerosis

Knockout of myostatin, a growth factor that limits muscle growth, can decrease body fat and promote resistance against developing atherosclerosis, or “hardening” of the arteries, according to a new study conducted in mice. The results will be presented Thursday at The Endocrine Society’s 91st Annual Meeting in Washington, D.C.

“Obesity increases the risk of atherosclerosis, which accounts for 75% of all cardiovascular events, such as heart attacks and strokes,” said study co-author Shalender Bhasin, MD, professor of medicine at Boston University School of Medicine and chief of the Section of Endocrinology, Diabetes, and Nutrition at Boston Medical Center. “Current strategies aimed at preventing heart disease consist primarily of lowering cholesterol levels, but patients reaching the desired cholesterol levels are still at risk for atherosclerosis if they have other risk factors, such as obesity.”

Humans and animals with a mutation in the myostatin gene are extremely muscular and have little fat, past research shows. Also, when the gene encoding myostatin is knocked out in mice, their muscle mass increases.

Bhasin and his co-workers wanted to find out if inhibiting myostatin in mice could resist the development of diet-induced obesity and of atherosclerosis, the buildup of lipid deposits called plaque that can narrow and clog coronary arteries.

The researchers took mice that were genetically altered to develop atherosclerosis and then cross-bred them with myostatin knockout mice. Ten generations later, they had mice who were genetically predisposed to both atherosclerosis and inactivation of myostatin. For controls, they studied mice with a genetic predisposition for atherosclerosis but with intact myostatin gene. All mice received a high-fat diet for 12 weeks, to spur the development of atherosclerosis.

Compared with controls, the mice with deleted myostatin gene had much less body fat and 30 percent lower fasting blood sugar and 80% lower fasting insulin levels, showing a reduction in obesity and a strong resistance to developing diabetes, the authors reported. They also had 50 percent lower low-density-lipoprotein (“bad”) cholesterol and 30 to 60 percent lower levels of total cholesterol and triglycerides (fats in the blood), respectively. These results indicate protection against the development of atherosclerosis, according to Bhasin.

More research is needed to demonstrate the safety and effectiveness of myostatin inhibitors in humans, Bhasin said. However, he said that that this therapeutic strategy already is possible. Experimental drugs called myostatin blockers or inhibitors are being studied as potential treatments of muscle wasting disorders and limb injuries.

Some currently available nutritional supplements are touted as myostatin inhibitors, but Bhasin said he doubts they are effective.

Wistar Institute team finds key target of aging regulator

Researchers at The Wistar Institute have defined a key target of an evolutionarily conserved protein that regulates the process of aging. The study, published June 11 in Nature, provides fundamental knowledge about key mechanisms of aging that could point toward new anti-aging strategies and cancer therapies.

Scientists have long known that a class of proteins called sirtuins promotes fitness and longevity in most organisms ranging from single-celled yeast to mammals. At the cellular level, sirtuins protect genome integrity, enhance resistance to adverse stresses, and antagonize senescence. However, the underlying molecular mechanisms have remained poorly understood. The team, led by senior author Shelley Berger, Ph.D., Hilary Koprowski Professor at The Wistar Institute, demonstrated for the first time a molecular target for a member of this class, Sir2, in regulation of aging in yeast cells. Sir2 removes an acetyl group attached to a specific site (lysine at position 16 or K16) on histone H4—histones are proteins that package and organize the long strands of DNA within the nucleus and also are central regulators in turning genes on and off. The study reveals that removal of this acetyl group by Sir2 near the chromosome ends—the telomeres—is important for yeast cells to maintain the ability to replicate. Researchers found that Sir2 levels decline as cells age, and there is a concomitant accumulation of the acetylation mark along with disrupted histone organization at telomeres.

Deacetylation of H4K16 by Sir2 and consequent telomere stability play a major role in maintaining long lifespan in yeast. Since sirtuins deacetylate many different proteins, these results clarify a key role of Sir2 protein in control of lifespan.

“Some modifications on histones, like this acetylation on histone H4 lysine 16, are persistent and are maintained through generations of cell divisions. This DNA-independent inheritance is called epigenetics,” Berger says. “Characteristic epigenetic features have been discovered for various developmental processes in recent years. Understanding epigenetic changes associated with aging is a hugely exciting direction in aging research. It will provide insights and ideas not only for new therapies to regulate cells that have lost control of proliferation, such as ‘immortal’ cells found in cancers, but also for new strategies to maintain health and fitness.”

“We plan to continue to search for new targets of Sir2 and other aging regulators,” says lead author Weiwei Dang, Ph.D., a postdoctoral scientist working with Berger. “We are designing unbiased screens for other aging targets and mechanisms in chromatin. Using yeast as our aging model enables us to do many discovery screens that are impossible with other, more complex organisms. Yet it is remarkable that many of these chromatin mechanisms associated with yeast could turn out to be relevant even for aging human cells.”

Like him or loathe him, he does get one excited about the future…

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