Aging is one SIRTainty in life: for uni- and multicelular lifeforms!

In Friday's issue of Cell magazine, an evolutionarily conserved protein, SIRT, takes the spotlight in the hit research drama, "Why we Weather with Age". Researchers from Harvard Medical school demonstrate that the part SIRT plays in DNA damage control during aging may be to blame for some of the ugly symptoms of growing old.

Mammalian protein SIRT, or SIR2 in unicellular yeast, normally sits on DNA to prevent unnecessary genes from being expressed in the wrong cells. Every gene is present in every cell in the body, but we wouldn't want our liver enzymes expressed in our brain cells. Thus, gene regulation is needed to determine the appropriate time and place for a gene to be expressed so that dangerous cellular consequences are avoided. SIR2 is a protein in yeast that has been known for years to silence inappropriate gene expression, but this key protein has another critical role to play during aging. SIRT is among the first responders to sites of DNA damage.

Needless to say, the older you get, the more DNA damage is present your cells: hence the wrinkles. So you might be grateful this Thanksgiving weekend that SIRT may be on task to fix those little DNA dings in your genetic machinery. Unfortunately, SIRT relocation to sites of DNA damage means the abandonment of its protective post on silenced genes. The unsilencing of unnecessary genes can have deleterious consequences for cells.

A consequence for aging yeast is sterility, which occurs when SIR2 goes AWOL to fix DNA damage, leaving a gene for sterility exposed and awaiting expression. This process has been studied well, but was thought to only be relevant to aging in yeast. Today's published findings by David Sinclair of Harvard Medical School and his colleagues demonstrate for the first time that the protective protein SIRT, works overtime in aging mice, picking up and moving to sites of DNA damage, while deserting the formerly repressed genes, which when expressed, are linked to various symptoms of aging.

Interestingly, when Sinclair feeds his mice a surplus of SIRT, they live significantly longer. “Our hypothesis was that with more [SIRT], DNA repair would be more efficient, and the mouse would maintain a youthful pattern [of] gene expression into old age.” Philipp Oberdoerffer, a researcher on Sinclair's team explains. Dr. Sinclair is working as a consultant for Genocea, Shaklee and Sirtris, a GSK company seeking to develop SIRT drugs for human use.

While we await a magical "forever young" drug, this publication serves as the first to suggest a shared mechanism for aging between two highly diverse organisms. The authors suggest the SIRT protein is a part of a universal mechanism for aging, which could be conserved across a variety of mammalian species, including humans. So as we begin to celebrate the close of yet another year, we can be hopeful that such mechanisms continue to be explored so that we might avoid the less desirable consequences of growing old.

image credit: http://www.cyber-heritage.co.uk/women/

Buried Martian Ice Discovered: Clues into the 'Life on Mars' Mystery?

Earthling's obsession with the possibility of life on Mars dates back to the 19th century, when Italian astronomer, Giovanni Schiaparelli believed that he observed long, narrow channels on the red planet. These crevasses were interpreted and popularized by author/astronomer Percival Lowell to be irrigation canals built by ancient civilizations of martians who were struggling to survive on a cooling, drying planet.

Of course modern science has since ruled out the possibility of intelligent civilizations existing on our planetary neighbor, yet the search for life on Mars is ongoing. Most astronomers agree that conditions for life on Mars were more suitable hundreds of millions of years ago. Thus NASA's primary goal for satellite and rover missions is to identify if liquid water existed on an ancient Mars.

With the release of Friday's issue of Science, there is now evidence of frozen water-ice buried beneath approximately ten meters of rocky Martian debris discovered, for the first time, outside of Mars' polar regions. Hundreds of these large glacier-like ice sheets, discovered by John Holt of University of Texas Austin and his colleagues using images collected from the Mars Reconnaissance Orbiter, lie covered by dirt and rock in the middle latitudes of Mars. Climate studies of past ice ages support the notion that these ice caps formed when Mars may have tipped on its axis to expose these middle latitudes to much colder conditions, which would have allowed for such massive glaciers to form. But what can these buried water-ice formations tell us about life on Mars?

These glaciers likely hold atmospheric records of ancient Martian climate, which could reveal whether conditions were ever suitable for life on Mars. Perhaps more intriguing is the idea that if life existed as these ice sheets formed, there could be microbial fossils preserved in the ice. Some might even contend that life could thrive in these formations under current conditions. While all of these ideas are still speculative and require further investigation, the identification of these ice caps is great news for future human explorers, who could potentially use the frozen water as a hydrogen energy source or for drinking water. And there's a lot of it to go around. "Just one of the features we examined is three times larger than the city of Los Angeles, and up to one-half mile thick, and there are many more," John Holt explained in a press release, attesting to the immensity of these ice formations.

A bit closer to home, NASA's Astrobiology Institute is leading an expedition this month into the "global warming hot-spots" of Bolivia and Chile, which serve as model systems for what conditions may have been like 3.5 billion years ago on Mars. Pictured on the right above, "the Atacama desert is the driest place on Earth," Kevin Rose, a University of Miami student/explorer explains,"By examining the most extreme environments on Earth, such as extremely high UV, low oxygen, low temperatures, and low pH, we can infer what life, if it existed, may have had to deal with on Mars."

With scientists working tirelessly on both sides of the interplanetary divide, the prospect of finding life on Mars is an increasingly exciting story to follow.

Photo source: www.current.com, & http://www.travelblog.org/South-America/Chile/Atacama/blog-277669.html

Fish on Prozac

While a story about mellow, happy fish may sound like a sport-fisherman's dream, Prozac in the water could prove to be a fish's worst nightmare. Fish and invertebrates living downstream of urban water and sewage treatment plants around the world have detectable levels of antidepressants in their systems. While actual concentrations in surface waters are low, the active ingredients from antidepressants such as Prozac are causing biochemical, neurological, and physiological damage to a variety of water dwelling creatures.

Pharmaceutical compounds that the human body doesn't metabolize are excreted, and can enter the environment via the septic super-highway, contaminating surface waters downstream. Unused medications are often flushed or trashed, which can increase the amount of these compounds in nature.

Antidepressants (often called SSRI's) block re-uptake of the neurotransmitter serotonin, an ancient and highly conserved chemical present in the brains of many creatures- from invertebrates to humans. At the Society of Environmental Toxicology and Chemistry meeting held this week in Tampa, FL, multiple groups of independent researchers presented evidence demonstrating the effects of SSRI drugs on the nervous systems of fish and invertebrates.

Aquatic life is trying- a never ending struggle between predator and prey. Thus it is important that fish be hyper-aware of their surroundings so that predators don't swallow them whole. In experiments run by Meghan McGee of St. Cloud University, fish that were treated with SSRI's showed impaired startle responses, suggesting that they could more easily fall victim to a predators attack. SSRI's don't help the predators either. Research by Joseph Bisesi, Jr. from Clemson University demonstrated that at high doses of these drugs, hybrid striped bass were significantly slower to capture their prey.

While antidepressants in the water are attracting a lot of attention, previous research has shown that hormones from birth control pills, also present in surface waters, can cause male fish to become reproductively feminized.

Concurrently, multiple health risk prediction studies estimate safe levels of various pharmaceutical compounds in drinking water, which is often purified from the surface and ground waters where potentially affected fish and invertebrates dwell. Because pharmaceuticals in surface waters pose no immediate threat to humans, ecologists and environmental scientists must struggle to bring this issue to the forefront in order to protect aquatic creatures.

Photo credit: Shelly Sanders http://www.betterphoto.com/gallery/dynoGall2.asp?catID=977

Medicinal Aging?

Compounds similar to THC, the psychoactive ingredient in marijuana, have been shown to reduce memory impairments in the aging brain. While marijuana is widely known to impair memory in the short-term, leading scientists from Ohio State University are contradicting this age-old dogma by investigating how endocannabinoids, the brain’s naturally occurring cannabis, can improve memory function in the long-term.

Emerging evidence, presented this week by OSU's Dr. Gary Wenk and his colleagues at the Society for Neuroscience meeting in Washington D.C., indicates that the development of a legally prescribed drug similar to THC could slow or even prevent the onset of Alzheimer’s disease.

Memory loss is a key feature of Alzhiemer’s disease, which affects brain areas critical for emotional processing and memory formation. Inflammation in these areas is thought to contribute to the memory loss seen in Alzhiemer’s disease and even in normal aging. The THC-like drug used by Dr. Wenk, WIN-55212-2 (WIN), has been shown previously to have anti-inflammatory effects in both young and old rats. More recently, this same drug has aided in neurogenesis, or the growth of new brain cells in a dish- a finding that suggests such a drug could help grow brand new cells in an actual aging brain. If these newly formed cells could then link up with existing neural networks, new memories could potentially be made. At least this is the hope.

Right now this research is done on rats, as WIN is not used in humans due to its psychoactive effects. Aged rats normally perform poorly in a memory task where visual cues are used to remind the rats where a hidden platform lies in a pool of water. Aged rats receiving non-psychoactive doses of WIN perform substantially better in this task. Additionally, the specific receptors that WIN targets have now been identified in the hippocampus, an area critical for new memory formation. WIN’s action on these receptors decreased inflammation in the hippocampus, an effect that could potentially contribute to the amelioration of memory loss in aged rats.

While such drugs are not yet legally available in the U.S., is it advisable for the millions of people with a family history of Alzhiemer’s to eagerly await the legalization of medicinal marijuana nationwide? The short answer is, no. “The end goal is not to recommend the use of THC in humans to reduce Alzheimer’s,” Dr. Yannick Marchalant, a member of Wenk’s team, advises. “We need to find exactly which receptors are most crucial, and ideally lead to the development of drugs that specifically activate those receptors. We hope a compound can be found that can target both inflammation and neurogenesis, which would be the most efficient way to produce the best effects.”

Photo source: The program for the 2nd International Cannabis and Mental Health Conference