US scientists say they have successfully reversed the effects of Alzheimer’s with experimental drugs.

The drugs target and boost the function of a newly pinpointed gene involved in the brain’s memory formation.

Read more here…

More evidence regarding the benefits of green tea consumption:

Chronic green tea consumption prevents age-related changes in rat hippocampal formation.

Neurobiol Aging. 2009 May 1.

Assunção M, Santos-Marques MJ, Carvalho F, Lukoyanov NV, Andrade JP.
Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.

The hippocampal formation undergoes considerable structural and functional modifications during aging and oxidative stress emerges as a key player in the process. In the present study, we investigated whether prolonged consumption of green tea (GT), which contains large amounts of polyphenols, could interfere with age-related changes in this brain region using biochemical, morphological and behavioral approaches. Ten male Wistar rats aged 19 months were fed with GT since 12 months of age and results compared to those obtained from controls aged 19 months (C-19M). At 12 months of age, another group of rats was evaluated to provide baseline data. Oxidative stress markers (protein carbonyls and malondialdehyde) were quantified in hippocampal homogenates and stereological methods were applied to estimate the deposition of lipofuscin in hippocampal CA3 pyramidal neurons. Morris water maze was used to assess spatial learning and memory. Aging increased oxidative markers and lipofuscin accumulation and was associated with impaired memory acquisition. However, GT treatment protected proteins and lipids against oxidation and prevented the increase of lipofuscin deposition compared to age-matched controls. Furthermore, the spatial learning abilities of GT-treated rats were significantly improved when compared to those from C-19M group. Taken together, these findings confirm the neuroprotective ability of GT in the hippocampal formation probably due to the reduction of oxidative stress-related damage observed during aging.

PMID: 19411127

This article from Neurobiological Aging reports that users of anti-inflammatory drugs not only have a reduced incidence of Alzheimer’s disease, but also show significantly less age-related brain atrophy, suggesting inflammation may be one of the causes of the cognitive decline commonly seen in the elderly.

Examples of anti-inflammatory substances include the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as aspirin, ibuprofen, and naproxen, and other substances like EPA and DHA from fish oil.

Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.

Neurobiol Aging. 2009 Apr 20. PMID: 19386384

Walther K, Bendlin BB, Glisky EL, Trouard TP, Lisse JR, Posever JO, Ryan L.
Cognition and Neuroimaging Laboratories, Department of Psychology, University of Arizona, Tucson, AZ, 85721, USA.

Previous studies have indicated a decreased risk for developing Alzheimer’s disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.

It’s always great when new uses are discovered for drugs that are already on the market, and such is the case with the osteoporosis drug Forteo (teriparatide), which is a recombinant form of parathyroid hormone.

It’s been discovered by researchers at the University of Rochester Medical Center (and reported here) that teriparatide boosts bone stem cell production to the point that adults’ bones heal at a much faster rate, similar to that of young children.

While this is likely to be of benefit to anyone with a fracture, it’s particularly useful for those with fractures that remain chronically unhealed. Teriparatide kick starts the process, and in a study of 145 patients with these kinds of recalcitrant breaks, 93% experienced marked healing and relief from pain in 8 to 12 weeks.

The clinical implication is significant, as orthopaedists can soon have a new tool at their disposable to deal with many common, painful bone ailments including the tens of thousands of painful fractures for which there is no treatment (pelvic fractures, vertebral compression fractures, clavicle fractures), fractures that won’t heal, fractures in patients that are either too sick to have surgery or chose not to have surgery, and even reduce the size of a incision in some surgeries.

While those of us averse to needles will be disappointed to learn that teriparatide is administered daily by (although reportedly painless) injection, the fact that this is a real drug, in production, approved, and available now is a refreshing change from most discoveries, which have to sit under the Christmas tree for the next 10 years.

When a fracture occurs, a bone becomes unstable and can move back and forth creating a painful phenomenon known as micromotion. As the bone begins healing it must progress through specific, well-defined stages. First, osteoclasts – cells that can break down bone – clean up any fragments or debris produced during the break. Next, a layer of cartilage – called a callus – forms around the fracture that ultimately calcifies, preventing the bony ends from moving, providing relief from the significant pain brought on by micromotion.
Only after the callus is calcified do the bone forming cells – osteoblasts – begin their work. They replace the cartilage with true bone, and eventually reform the fracture to match the shape and structure of the bone into what it was before the break.

Teriparatide speeds this process by speeding up the formation of the callus and stimulating the osteoblasts, the cells that produce bone, to produce more bone and faster. The completion of the formation of the callus is the milestone at which point the pain of the injury is markedly diminished as it stops the micromovement of the fracture that generates the pain.

All in all, teriparatide more than halved the normal healing time for the patients.

Photo credit: KooshKing on Flickr

Some of you may be aware that the the antibiotic doxycycline hyclate has been found to possess anti-matrix metalloproteinase (MMP) activities. MMPs are the enzymes that break down connective tissue such as collagen, and their relative increase is thought to contribute to the development of wrinkles in aged skin.

This is because, while the ability to degrade the matrix is extremely important in growth and wound healing, if the processes of synthesis and degradation fall out of balance in favour of degradation, the overall amount of collagen will decrease.

In youth, these processes are in balance, but as we age, the degradative enzyme activity begins to overpower that of synthesis, leading to a loss of skin quality. Other factors that increase MMPs are photodamage and smoking.

In the past, I’ve boosted my skin’s balance in favour of collagen synthesis with isotretinoin, which worked beautifully but has drawbacks that in my opinion make it unacceptable for chronic use (cracking lips, sun sensitivity, etc.). I’ve also heard that the skin’s response to collagen-synthesis stimulating retinoids decreases with age.

So, in theory, one could boost its overall levels by instead interfering with the breakdown of collagen by inhibiting MMPs.

At present, the only MMP inhibitor that’s available readily and cheaply is doxycycline hyclate, an antibiotic often used to combat acne. Apparently, by taking a subantimicrobial dose (i.e., too little to kill bacteria) one can benefit from its anti-MMP activity while minimizing its side effects. Doxycycline is also used in this way in dentistry, where it is used to facilitate healing of the connective tissue in the gums.

There was also a study where doxycycline’s effect on wound healing was investigated because it was suspected it may *interfere* with normal wound healing as a side-effect, but it was instead found that the wounds actually healed either at the same rate or faster.

So, lately I’ve been noticing the accumulation with age and decades of intense sunlight a slight loss of skin elasticity (yes, wrinkles), so I decided to start taking 25mg/day doxycycline for a couple of months and see if this has any effect on the quality of my skin. I’ve taken some ‘before’ photos that highlight the problem, and I intend to compare these with pictures taken in 1 and 2 months to see if I can identify any change.

The literature is at first glance almost entirely free of this kind of experiment, with most papers focussing on doxycycline’s antibacterial and anti-inflammatory effects for the treatment of acne and rosacea. I’m sure there’s a good reason for this that I in my limited capacity don’t have time to dig up, so I’m pressing ahead regardless.

I’ll post the results, including before/after shots and analysis in about a month

Here’s some reading in the meantime:

• Inhibition of matrix metalloproteinases: a new skin care frontier
• Matrix metalloproteinases
• Doxycycline

Just thought I’d share this article: Computer Program Self-Discovers Laws of Physics, which just appeared on Wired Science. It’s about an AI that can derive laws of physics by analyzing data sets.

Scaled up, the possibilities of something like this would be amazing… this really offers us a glimpse of the nature of the technological singularity, where AI computers are the new scientists, iteratively, exponentially improving themselves (and us, hopefully) beyond prediction and comprehension.

I can’t wait!

Two commonly administered substances were today attributed with some new anti-cancer properties: tetrahydrocannabinol (THC), the main active constituent of cannabis, and docosahexaenoic acid (DHA), an omega-3 fatty acid found in fish oil.

Reported in the Journal of Clinical Investigation, THC was shown to induce human glioma (brain cancer) cell death through a process known as autophagy, and did so by activating a particular stress response in the cells.

DHA, in an article soon to be published in Cell Division, was shown to reduce the size of tumours and enhance the positive effects of the chemotherapy drug Cisplatin. In particular, DHA strongly mitigated the toxic effect of Cisplatin on the kidneys while simultaneously increasing its effectiveness against cancer cells.

Of course, both substances – especially cannabinoids – have been attributed with anti-cancer properties for quite a while, but it’s always good to obtain further insight into the mechanisms by which these effects are exerted, particularly with cannabis, which is often difficult to research on account of its illegality in many parts of the world.

Anyhow, I’m cheered: at the rate I’m going, I don’t think I’ll ever get brain cancer

Research emanating from the Linus Pauling Institute at Oregon State University and published in the Archives of Biochemistry and Biophysics has shown that dietary supplementation with lipoic acid lowered plasma triglyceride levels up to 60 percent in rats. While the extent of the effect is yet to be determined in humans; if similar, lipoic acid could be considered to be as effective in this regard as certain prescription medications.

Triglycerides are what the body converts dietary fat into in the intestines so that it can be transported in the bloodstream (packaged with cholesterol and proteins to form chylomicrons, which emulsify in the blood to be transported to the tissues for energy production and storage). It is believed that the fatty buildup in the arteries known as atherosclerosis can be attributed in part to the levels of triglycerides in the bloodstream.

In this experiment, it was found that lipoic acid supplementation dramatically reduced the amount of circulating triglycerides via two pathways – it increased the rate at which they were removed from the blood, and it reduced the production of triglycerides in the liver by reducing the number of enzymes that synthesize them.

Lipoic acid has also been shown in cell culture experiments to increase the cellular uptake of glucose by recruiting the glucose transporter GLUT4 to the cell membrane; and of course, rat aging studies have suggested that the use of L-carnitine and lipoic acid in combination results in improved memory performance and delayed structural mitochondrial decay.

According to the press release, the amount of lipoic acid supplementation used in these experiments would equate to about two grams per day for a 150-pound (68 kg) person (the article claims 200mg/kg for the rats, so they’re dividing by a factor of 8 to account for metabolic differences between rats and humans). Also of note is their use of R-alpha-lipoic acid (not the S enantiomer or the racemate).

Personally, I take the sodium salt of r-alpha-lipoic acid (Na-RALA), but nowhere near the 2g/day recommended here… more like 600mg/day. At the current price of about USD 1/gram for the bulk powder, such a regimen seems a bit expensive.

You might have, at some stage, encountered the idea that the lifespan of an animal is related to its rate of energy consumption; i.e., that the faster its metabolism, the shorter an animal lives. I’ve also heard it said that all animals get a certain number of heartbeats in life and the sooner they use them up, the sooner they die. This might explain why an elephant lives longer than a mouse, but new evidence has hammered a fairly convincing nail in the coffin of this theory.

In this press release, Live Fast, Die Young, Maybe Not…, it talks about an experiment whereby two groups of mice were made to live under different conditions of temperature – 22 degrees and 10 degrees Celsius, respectively, the rationale being that the cold mice would have to expend more energy throughout their lives simply to stay warm. The mice were then evaluated as to their longevity.

There was found to be no significant difference in longevity between the two groups.

Despite a 48 percent increase in overall daily energy expenditure and a 64 percent increase in mass-specific energy expenditure throughout adult life, mice in the cold lived just as long on average as mice in warm temperatures. These results strengthen existing doubts about the rate-or-living theory.

So, while I always strongly doubted this theory (how could a parrot live so much longer than a dog?), it still played in the back of my mind that expending a great deal of energy on exercise and whatnot would burn my body out and lead to a shorter lifespan. Hopefully, I can now lay those fears to rest once and for all!

An article appearing recently in the World Journal of Gastroenterology penned by the team led by Professor Sayed-Ahmed from the College of Pharmacy, King Saud University, has reported on the role of carnitine in the liver during the development of liver cancer (hepatocarcinogenesis). Apparently, carnitine deficiency is a risk factor and critical to the mechanism of hepatocarcinogenesis, and long-term L-carnitine supplementation could prevent, slow, or reverse its occurrence.

L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources: endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production.

To test their hypothesis, the researchers studied a rat model of hepatocarcinogenesis under conditions of carnitine deficiency and supplementation.

L-carnitine supplementation resulted in a complete reversal of the cancer-related changes in the rats’ livers.

Given these promising results, they intend to conduct further investigations into the mechanisms behind carnitine’s anti liver cancer effect.

Carnitine supplementation, particularly in the form of acetyl-L-carnitine (ALCAR), which is cheaply available from a number of suppliers, has a reasonably long history of conferring health and longevity benefits. In my opinion, it’s one of the cornerstones of an effective supplementation regime, particularly in combination with alpha lipoic acid (ALA).