Fine wrinkles, deeper creases, saggy areas around the mouth and neck – the sights in the mirror that make baby boomers wince – are not inevitable. They result from a structural breakdown inside the skin that some existing treatments effectively counteract by stimulating the growth of new, youthful collagen, University of Michigan scientists say.

The researchers report an emerging picture of collagen collapse and possible renewal, based on more than a decade of studies, in the May issue of Archives of Dermatology.

The article draws on dozens of studies since the early 1990s, conducted primarily by U-M dermatologists, to explain why three types of available skin treatments are effective: topical retinoic acid, carbon dioxide laser resurfacing and injections of cross-linked hyaluronic acid.

These treatments all improve the skin’s appearance – and its ability to resist bruises and tears – by stimulating new collagen. Collagen is a key supporting substance, plentiful in young skin, that’s produced in the sub-surface layer of skin known as the dermis. The U-M findings show that the breakdown of the dermis’ firm, youthful structure is a very important factor in skin aging – a much more straightforward thing to fix than genetic factors that others theorize may be involved.

“Fibroblasts are not genetically shot,” says John J. Voorhees, M.D., F.R.C.P., chair of the Department of Dermatology at the U-M Medical School and the article’s senior author. Fibroblast cells in the skin are the key producers of collagen.

“We have shown that if you make more collagen go in, it provides an environment in which fibroblasts recover and make more collagen.”

Voorhees and co-authors Gary J. Fisher, Ph.D., U-M professor of dermatology, and James Varani, Ph.D., U-M professor of microbiology and immunology and pathology, hope the findings will help people make intelligent decisions amid the hype of the multi-billion-dollar anti-aging products industry. Fisher directs the U-M Photoaging and Aging Research Program.

“We want to educate clinicians about what’s been found, and what it means in terms of how we may improve the appearance of people,” says Voorhees, the Duncan and Ella Poth Distinguished Professor of Dermatology at U-M.

Young vs. old skin

Collagen formation and breakdown takes place in the dermis or inner skin, the thicker, firm layer of skin that lies beneath the paper-thin outer skin or epidermis, much as a mattress lies beneath a sheet. Collagen consists of proteins that make up a supporting structure surrounding the skin cells. In youthful skin, collagen is firm, taut and abundant, like a new mattress. In older skin, the collagen structure begins to fall away, says Voorhees.

Just as a foam mattress over time becomes flatter in places and creased as its structure breaks down, aging skin begins to sag and wrinkle when its collagen is diminished and fragmented. The cycle of events involved in collagen loss is complicated.

As skin ages, reactive oxygen species, associated with many aspects of aging, lead to increased production of the enzyme collagenase, which breaks down collagen. Then fibroblasts, the critical players in firm, healthy skin, lose their normal stretched state. They collapse, and then more breakdown enzymes are produced. People in their 80s have four times more broken collagen than people in their 20s.

“What it’s doing is dissolving your skin,” Voorhees says. “What you’ve got is a vicious cycle. You have to interrupt it, or aging skin is just going downhill.”

In the elderly, in whom the dermis has lost two-thirds or more of its youthful thickness through collagen loss, skin tears and bruises easily. Collagen-building interventions thus have potential for reducing basic health problems such as bed sores, in addition to improving appearance.

A growing body of evidence

The U-M researchers base their conclusions on past studies in which they have explored why certain anti-aging treatments are effective. A 2007 study looked at Restylane, marketed as a dermal filler, and found that injections of the product caused fibroblasts to stretch, promoting new collagen, and also limited the breakdown of collagen.

In another 2007 study, the U-M team tested lotions containing retinol, a form of Vitamin A found in many skin-care products, and found it significantly reduced wrinkles and skin roughness in elderly skin by promoting new collagen. Other U-M studies have shown why some laser treatments work and some less powerful ones do not. Carbon dioxide laser resurfacing is effective because it removes the aging dermis; in the three-week regrowth process, new, young collagen is produced.

Voorhees and his colleagues say they provide needed, independent research on the effectiveness of available and future treatments to counteract skin aging. They have no ties to the manufacturers of products they study.

Seafloor bacteria on ocean-bottom rocks are more abundant and diverse than previously thought, appearing to "feed" on the planet's oceanic crust, according to results of a study reported in this week's issue of the journal Nature.

The findings pose intriguing questions about ocean chemistry and the co-evolution of Earth and life.

Once considered a barren plain dotted with hydrothermal vents, the seafloor's rocky regions appear to be teeming with microbial life, say scientists from the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Mass., University of Southern California (USC) in Los Angeles, and other institutions.

While seafloor microbes have been detected before, this is the first time they have been quantified. Using genetic analyses, Cara Santelli of WHOI, Katrina Edwards of USC, and colleagues found three to four times more bacteria living on exposed rock than in the waters above.

"Initial research predicted that life could in fact exist in such a cold, dark, rocky environment," said Santelli. "But we really didn't expect to find it thriving at the levels we observed."

Surprised by this diversity, the scientists tested more than one site and arrived at consistent results, making it likely, according to Santelli and Edwards, that rich microbial life extends across the ocean floor.

"This may represent the largest surface area on Earth for microbes to colonize," said Edwards.

"These scientists used modern molecular methods to quantify the microbial biomass and estimate the diversity of microbes in deep-sea environments," said David Garrison, director of the National Science Foundation (NSF)'s Biological Oceanography Program. NSF's Ridge 2000 program funded the research. "We now know that this remote region is teeming with microbes, more so than anyone had guessed."

Santelli and Edwards also found that the higher microbial diversity on ocean-bottom rocks compared favorably with other life-rich places in the oceans, such as hydrothermal vents.

These findings raise the question of where these bacteria find their energy, Santelli said.

"We scratched our heads about what was supporting this high level of growth," Edwards said.

With evidence that the oceanic crust supports more bacteria than overlying water, the scientists hypothesized that reactions with the rocks themselves might offer fuel for life.

In the lab, they calculated how much biomass could be supported by chemical reactions with the rocky basalt. They then compared this figure to the actual biomass measured. "It was completely consistent," Edwards said.

This discovery lends support to the idea that bacteria survive on energy from Earth's crust, a process that could add to our knowledge about the deep-sea carbon cycle and the evolution of life.

Many scientists believe that shallow water, not deep water, is better suited for cradling the planet's first life forms. Up until now, dark, carbon-poor ocean depths appeared to offer little energy, and rich environments like hydrothermal vents were thought to be relatively sparse.

But the newfound abundance of seafloor microbes makes it possible that early life thrived--and perhaps began--on the seafloor.

"If we can really nail down what's going on, there are significant implications," Edwards said. "I hope that people turn their heads and notice: there's life down there."

Until recently, the animal - a shrimplike, energy-dense creature called Diporeia - was a major food source for commercially important species like lake whitefish and many prey fish upon which salmon, trout and walleye rely.

Scientists are employing new research methods in a quest to explain their population freefall, which threatens to negatively affect the Lakes' ecosystems and $4 billion sport fishing industry, said Purdue University researcher Marisol Sepúlveda.

"We want to narrow down likely causes for this decline," said Sepúlveda, an assistant professor of forestry and natural resources. "It may help us halt the animal's further disappearance."

Sepúlveda has begun to identify substances involved in Diporeia metabolism, the set of chemical reactions that maintain life and allow organisms to respond to stress. Differences in levels of these metabolites between individuals and populations in various regions of the lakes may point toward the stressor or stressors responsible for their decline, she said.

In the same biological class as krill and shrimp, these rice grain-sized crustaceans dwell on lake bottoms and feed on descending algal plankton. Their bodies contain 30 percent to 40 percent lipids like fats and oils, making them a vital energy and nutrient source for the entire food web.

They are already gone from many large areas of lakes Michigan, Huron, Erie and Ontario, said collaborating researcher Tom Nalepa. In Lake Michigan, there are almost no Diporeia found at depths shallower than 90 meters. Just 15 years ago, their density often exceeded 10,000 animals per square meter at such depths, said Nalepa, a research biologist with the Great Lakes Environmental Research Laboratory.

The spread of invasive zebra and quagga mussels - voracious filter feeders with an overlapping diet - largely coincides with Diporeia's decline and is widely believed to be at least partially responsible. But research cannot yet explain the link, Nalepa said.

"We don't know why Diporeia are responding so negatively to the mussels," he said.

Sepúlveda is looking into another possible contributor to Diporeia's decline: water pollutants like pesticides, polychlorinated biphenyls (PCBs), flame retardants or others.

Detailed in a study to be published in print and online next month in the journal Aquatic Toxicology, Sepúlveda measured Diporeia's response to a common pollutant and also began to identify differences between declining populations in Lake Michigan and those native to Lake Superior, the only Great Lake where populations remain stable. The latter comparison found the groups shared only 5 percent of their total metabolites, suggesting that animals from the two lakes are biologically quite different, Sepúlveda said.

"The answer to Diporeia decline may be found in these variations," she said.

Sepúlveda and University of Michigan researcher Tomas Hook were awarded a four-year, $560,000 grant by the Great Lakes Fishery Trust in January of this year to further investigate possible causes for Diporeia's decline. Both researchers are co-principal investigators of the project.

"We are casting a wide net to basically address a number of hypotheses at the same time," said Hook, a fisheries ecologist hired by Purdue who will begin work there this July.

In Sepúlveda's study, she and her team contrasted levels of metabolites between a group of control animals and that of an atrazine-exposed population of laboratory-reared Diporeia. They found that animals subjected to atrazine, a commonly used pesticide present in minute levels in Lake Michigan, significantly increased or decreased bodily production of five identifiable chemicals. These included an insect pheromone, a fatty acid, an amino acid and a hydrocarbon, she said.

"We are just beginning to interpret these data, but they give us a better idea of how pollutants affect them," Sepúlveda said. "If nothing else, our results suggest that seemingly insignificant levels of pollution could significantly harm animals like Diporeia."

The project should help address suggestions by some researchers that Diporeia and/or invasive zebra and quagga mussels may be capable of bioaccumulating or affecting levels of pollutants in a way that might intensify their harmful effects, Sepúlveda said.

The project also should deepen understanding of exactly how the invasive mussels hurt Diporeia, Hook said. Researchers have looked into, but have yet to determine, the extent to which the mussels outcompete the crustaceans for food, contaminate their surroundings with their effusive waste material, or influence the transmission and spread of diseases.

Regardless of the reason, Diporeia's decline has already had some measurable negative effects on various fish species. Alewives, an important prey fish that provides Chinook salmon well over 80 percent of its food, have declined in growth rates, condition - measured as the ratio of weight to length - and caloric density since Diporeia populations began declining, said Charles Madenjian, research fishery biologist with the United States Geologic Survey.

"Alewives used to regularly reach 10 inches in length," Madenjian said. "Now we're lucky to find one that breaks 8 inches."

Diporeia previously supplied 50 percent of the food source for the commercially important lake whitefish and now supply only about 5 percent. Since the crustacean's decline began in the 1990s, growth rates and the condition of lake whitefish have substantially fallen off, Madenjian said.

If Diporeia's decline proves to have similar negative consequences upon other species and continues to worsen, the most severe effects may be forthcoming, although it is difficult to predict such outcomes with any certainty, Nalepa said.

Hook said he believes the initial step in taking action is to pinpoint causes.

"The first thing we can do is find out more precisely why they are declining," he said. "If we guess, any management decision we make could be counterproductive."

Zebra and quagga mussels were almost certainly spread to the Great Lakes from Europe or East Asia in the fresh water ballasts of oceangoing vessels, beginning in the late 1980s, Nalepa said. People need to be aware of the risks of spreading harmful invasive species and such ballasts should be more tightly regulated or possibly banned, he said. In one simple preventive measure, boats exchange their freshwater ballast for salt water ballast in the open ocean, thereby killing any freshwater species present.

The study by Sepúlveda used a process called gas chromatography to separate metabolites and matched them with known chemicals on a national database. Researchers identified 76 metabolites among lake-dwelling animals and 302 among the control and atrazine laboratory populations. Results from the two comparative analyses suggest that fatty acids and hydrocarbons are important to the animal's survival or may be interfered with by particular stressors.

Diporeia put on much of their weight during the spring bloom of diatoms, algal plankton they feed upon, during which energy capture and storage are particularly paramount. This leaves them vulnerable to disruptions in food or their ability to store it, a process in which fatty acids play a key role, Sepúlveda said.

How to beat jet lag: don't eat, researchers suggest.

In addition to the light-driven circadian clock that regulates the body in response to changes in night and day, the mouse brain contains a second, separate clock that keeps track of mealtime, scientists say.

This clock, which resides in a different brain structure than the light-driven clock, probably takes over when food is scarce, changing the animals' behavior patterns so that they don't sleep through an opportunity to eat.

Scientists have long argued about whether or not the Earth has some special characteristics that led to the evolution of life. PhD researcher Jose Robles and Dr Charley Lineweaver from the Planetary Science Institute at ANU contend that this is a difficult question to answer because we don’t have information about other Earth-like planets.

“Yet the question ‘How special is the Sun?’ is easier to address because we do have observations of thousands of other Sun-like stars,” explains Dr Lineweaver.

Rather than guess what properties a star should have to enable life, the researchers decided to compare the Sun – which already hosts a life bearing planet – to other stars.

“Our research goes further than previous work which only looked at single properties such as mass or iron content,” says Robles, who is the lead author on the research paper. “We looked at 11 properties that could plausibly be connected with life and did an analysis of these properties: The upshot is that there doesn’t seem to be anything special about the Sun. It seems to be a random star that was blindly pulled out of the bag of all stars.”

The researchers found that the Sun’s mass is the most anomalous of its properties; the Sun is more massive than 95 per cent of stars. The Sun’s orbit around the centre of the galaxy is also more circular than the orbits of 93 per cent of its peers. “But when analysing the 11 properties together, the Sun shows up as a star selected at random, rather than one selected for some life-enhancing property,” Robles says.

The research is part of the ongoing scientific understanding of our place in the universe. “Those who are searching for justification for their beliefs that terrestrial life and humanity in particular are special, will probably interpret this result as a humiliating dethronement,” says Dr Lineweaver. “Those who believe we are the scum of the universe, may find our non-special status uplifting.”