Common antioxidant could slow symptoms of aging in human skin

These cross-section images show three-dimensional human skin models made of living skin cells. Untreated model skin (left panel) shows a thinner dermis layer (black arrow) compared with model skin treated with the antioxidant methylene blue (right panel). A new study suggests that methylene blue could slow or reverse dermal thinning (a sign of aging) and a number of other symptoms of aging in human skin. (credit: Zheng-Mei Xiong/University of Maryland)

University of Maryland (UMD) researchers have found evidence that a common, inexpensive, and safe antioxidant chemical called methylene blue could slow the aging of human skin, based on tests in cultured human skin cells and simulated skin tissue.

“The effects we are seeing are not temporary. Methylene blue appears to make fundamental, long-term changes to skin cells,” said Kan Cao, senior author on the study and an associate professor of cell biology and molecular genetics at UMD.

The researchers tested methylene blue for four weeks in skin cells from healthy middle-aged donors, as well as those diagnosed with progeria — a rare genetic disease that mimics the normal aging process at an accelerated rate. The researchers also tested three other known antioxidants: N-Acetyl-L-Cysteine (NAC), MitoQ and MitoTEMPO (mTEM).

In these experiments, methylene blue outperformed the other three antioxidants, improving several age-related symptoms in cells from both healthy donors and progeria patients. The skin cells (fibroblasts, the cells that produce the structural protein collagen) experienced a decrease in damaging molecules known as reactive oxygen species (ROS), a reduced rate of cell death, and an increase in the rate of cell division throughout the four-week treatment.

Improvements in skin cells from older donors (>80 years old)

Next, Cao and her colleagues tested methylene blue in fibroblasts from older donors (>80 years old), again for a period of four weeks. At the end of the treatment, the cells from older donors had experienced a range of improvements, including decreased expression of two genes commonly used as indicators of cellular aging: senescence-associated beta-galactosidase and p16.

Schematic illustrations of top (left panel) and side (right panel) views of the engineered 3D skin tissue cultured on a microporous membrane insert, used for experiments and skin-irritation tests (credit: Zheng-Mei Xiong et al./Scientific Reports)

The researchers then used simulated human skin to perform several more experiments. This simulated skin — a three-dimensional model made of living skin cells — includes all the major layers and structures of skin tissue, with the exception of hair follicles and sweat glands. The model skin could also be used in skin irritation tests required by the Food and Drug Administration for the approval of new cosmetic products, Cao said.

“This system allowed us to test a range of aging symptoms that we can’t replicate in cultured cells alone,” Cao said. “Most surprisingly, we saw that model skin treated with methylene blue retained more water and increased in thickness—both of which are features typical of younger skin.”

Formulating cosmetics

The researchers also used the model skin to test the safety of cosmetic creams with methylene blue added. The results suggest that methylene blue causes little to no irritation, even at high concentrations. Encouraged by these results, Cao and colleagues hope to develop safe and effective ways for consumers to benefit from the properties of methylene blue.

“We have already begun formulating cosmetics that contain methylene blue. Now we are looking to translate this into marketable products,” Cao said. “Perhaps down the road we can customize the system with bioprinting, such that we might be able to use a patient’s own cells to provide a tailor-made testing platform specific to their needs.”

The study was published online in the Nature journal Scientific Reports on May 30, 2017.

This research was supported by the Maryland Innovation Initiative.

Abstract of Anti-Aging Potentials of Methylene Blue for Human Skin Longevity

Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.

3D-printed ‘bionic skin’ could give robots and prosthetics the sense of touch

Schematic of a new kind of 3D printer that can print touch sensors directly on a model hand. (credit: Shuang-Zhuang Guo and Michael McAlpine/Advanced Materials )

Engineering researchers at the University of Minnesota have developed a process for 3D-printing stretchable, flexible, and sensitive electronic sensory devices that could give robots or prosthetic hands — or even real skin — the ability to mechanically sense their environment.

One major use would be to give surgeons the ability to feel during minimally invasive surgeries instead of using cameras, or to increase the sensitivity of surgical robots. The process could also make it easier for robots to walk and interact with their environment.

Printing electronics directly on human skin could be used for pulse monitoring, energy harvesting (of movements), detection of finger motions (on a keyboard or other devices), or chemical sensing (for example, by soldiers in the field to detect dangerous chemicals or explosives). Or imagine a future computer mouse built into your fingertip, with haptic touch on any surface.

“While we haven’t printed on human skin yet, we were able to print on the curved surface of a model hand using our technique,” said Michael McAlpine, a University of Minnesota mechanical engineering associate professor and lead researcher on the study.* “We also interfaced a printed device with the skin and were surprised that the device was so sensitive that it could detect your pulse in real time.”

The researchers also visualize use in “bionic organs.”

A unique skin-compatible 3D-printing process

(left) Schematic of the tactile sensor. (center) Top view. (right) Optical image showing the conformally printed 3D tactile sensor on a fingertip. Scale bar = 4 mm. (credit: Shuang-Zhuang Guo et al./Advanced Materials)

McAlpine and his team made the sensing fabric with a one-of-a kind 3D printer they built in the lab. The multifunctional printer has four nozzles to print the various specialized “inks” that make up the layers of the device — a base layer of silicone**, top and bottom electrodes made of a silver-based piezoresistive conducting ink, a coil-shaped pressure sensor, and a supporting layer that holds the top layer in place while it sets (later washed away in the final manufacturing process).

Surprisingly, all of the layers of “inks” used in the flexible sensors can set at room temperature. Conventional 3D printing using liquid plastic is too hot and too rigid to use on the skin. The sensors can stretch up to three times their original size.

The researchers say the next step is to move toward semiconductor inks and printing on a real surface. “The manufacturing is built right into the process, so it is ready to go now,” McAlpine said.

The research was published online in the journal Advanced Materials. It was funded by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.

* McAlpine integrated electronics and novel 3D-printed nanomaterials to create a “bionic ear” in 2013.

** The silicone rubber has a low modulus of elasticity of 150 kPa, similar to that of skin, and lower hardness (Shore A 10) than that of human skin, according to the Advanced Materials paper.

College of Science and Engineering, UMN | 3D Printed Stretchable Tactile Sensors

Abstract of 3D Printed Stretchable Tactile Sensors

The development of methods for the 3D printing of multifunctional devices could impact areas ranging from wearable electronics and energy harvesting devices to smart prosthetics and human–machine interfaces. Recently, the development of stretchable electronic devices has accelerated, concomitant with advances in functional materials and fabrication processes. In particular, novel strategies have been developed to enable the intimate biointegration of wearable electronic devices with human skin in ways that bypass the mechanical and thermal restrictions of traditional microfabrication technologies. Here, a multimaterial, multiscale, and multifunctional 3D printing approach is employed to fabricate 3D tactile sensors under ambient conditions conformally onto freeform surfaces. The customized sensor is demonstrated with the capabilities of detecting and differentiating human movements, including pulse monitoring and finger motions. The custom 3D printing of functional materials and devices opens new routes for the biointegration of various sensors in wearable electronics systems, and toward advanced bionic skin applications.

New 3D printing method may allow for fast, low-cost, more-flexible medical implants for millions

UF Soft Matter | Silicone is 3D-printed into the micro-organogel support material. The printing nozzle follows a predefined trajectory, depositing liquid silicone in its wake. The liquid silicone is supported by the micro-organogel material during this printing process.

University of Florida (UF) researchers have developed a method for 3D printing soft-silicone medical implants that are stronger, quicker, less expensive, more flexible, and more comfortable than the implants currently available. That should be good news for the millions of people every year who need medical devices implanted.

Model 3D-printed silicone trachea implant (credit: University of Florida)

Currently, such devices — such as ports for draining bodily fluids (cerebral spinal fluid in hydrocephalus, for example), implantable bands, balloons, soft catheters, slings and meshes — are mass produced and made through molding processes. To create customized parts for individual patients with molding would be very expensive and could take days or weeks for each job.

The 3D printing method cuts that time to hours, potentially saving lives.

The ability to easily replace silicone implants at low cost is especially important for children, where “implants may need to be replaced frequently as they grow up,” Thomas E. Angelini, an associate professor of mechanical engineering  of the UF Department of Mechanical and Aerospace Engineering, explained to KurzweilAI. Angelini is senior author of a paper published May 10, 2017 in the open-access journal Science Advances.

The research could also pave the way for new therapeutic devices that encapsulate and control the release of drugs or small molecules for guiding tissue regeneration or assisting diseased organs, such as the pancreas or prostate, according to lead author Christopher O’Bryan, a UF mechanical and aerospace engineering doctoral student.

UF Soft Matter | Water is pumped from one reservoir to another using a 3D-printed silicone valve. The silicone valve contains two encapsulated ball valves that allow water to be pumped through the valve by squeezing the lower chamber. The silicone valve demonstrates the ability of the UF 3D-printing method to create multiple encapsulated components in a single part — something that cannot be done with a traditional 3D-printing approach.

Abstract of Self-assembled micro-organogels for 3D printing silicone structures

The widespread prevalence of commercial products made from microgels illustrates the immense practical value of harnessing the jamming transition; there are countless ways to use soft, solid materials that fluidize and become solid again with small variations in applied stress. The traditional routes of microgel synthesis produce materials that predominantly swell in aqueous solvents or, less often, in aggressive organic solvents, constraining ways that these exceptionally useful materials can be used. For example, aqueous microgels have been used as the foundation of three-dimensional (3D) bioprinting applications, yet the incompatibility of available microgels with nonpolar liquids, such as oils, limits their use in 3D printing with oil-based materials, such as silicone. We present a method to make micro-organogels swollen in mineral oil, using block copolymer self-assembly. The rheological properties of this micro-organogel material can be tuned, leveraging the jamming transition to facilitate its use in 3D printing of silicone structures. We find that the minimum printed feature size can be controlled by the yield stress of the micro-organogel medium, enabling the fabrication of numerous complex silicone structures, including branched perfusable networks and functional fluid pumps.

A ‘smart contact lens’ for diabetes and glaucoma diagnosis

Smart contact lens on mannequin eye (credit: UNIST)

Korean researchers have designed a “smart contact lens” that may one day allow patients with diabetes and glaucoma to self-monitor blood glucose levels and internal eye pressure.*

The study was conducted by researchers at Ulsan National Institute of Science and Technology (UNIST) and Kyungpook National University School of Medicine, both of South Korea.

Most previously reported contact lens sensors can only monitor a single analyte (such as glucose) at a time, and generally obstruct the field of vision of the subject.

The design is based on transparent, stretchable sensors that are deposited on commercially available soft-contact lenses.

Electrodes based on a hybrid graphene-silver nanowire material can measure glucose in tears. Internal eye pressure changes are measured by a sandwich structure whose electronic characteristics are modified by pressure.

Inductive coupling — batteries not required

Both of these readings are transmitted wirelessly using “inductive coupling” (similar to remote charging of batteries), so no connected power source, such as a battery, is required. This design also allows for 24-hour real-time monitoring by patients.

The researchers conducted in-vivo and in-vitro performance tests using a live rabbit and bovine eyeball.

The team expects that the research could also lead to developing biosensors capable of detecting and treating various other human diseases, or used as a component in other biomedical devices.

The study results were published in the March issue of the journal Nature Communications. The study was supported by the 2017 CooperVision Science and Technology (S&T) Awards Program.

* Diabetes is the most common cause of high blood sugar levels. Intraocular pressure is the largest risk factor for glaucoma, a leading cause of human blindness.

How the smart contact lens works

Schematic of the top portion of the wearable contact-lens sensor. Left: antenna. Insert: Glucose sensor, based on a field-effect transistor (FET), which consists of a graphene channel and graphene/silver nanowire for source/drain. Not shown: chromium/gold interconnect, epoxy layer, and lens (below). (credit: UNIST)

Real-time glucose sensing with graphene/silver hybrid nanostructures. For selective and sensitive detection of glucose, glucose oxidase (GOD) catalyzes oxidation of glucose to gluconic acid and reduction of water to hydrogen peroxide, which produces oxygen, protons and electrons. The concentration of charge carriers in the FET channel, and thus the drain current, increases at higher concentration of glucose. (credit: UNIST)

The FET sensor (right) is modeled as an electrical RLC resonant circuit, comprised of the resistance (R) of the graphene channel, the inductance (L) of the antenna coil made of the graphene-AgNW hybrid, and the capacitance (C) of graphene-AgNW hybrid S/D electrodes. Wireless operation is achieved by mutually coupling the sensor antenna (center) with an external reader antenna (left) at a resonant frequency of 4.1 GHz. (credit: UNIST)

Schematic of intraocular pressure monitoring. A layer of silicone elastomer  was placed between the two inductive spirals made of graphene-AgNW hybrid electrodes in a sandwich structure. The contact lens sensor responds to raised intraocular pressure (ocular hypertension), which increases the corneal radius of curvature, which in turn increases both the capacitance by thinning the dielectric and the inductance by bi-axial lateral expansion of the spiral coils. As a result, ocular hypertension shifts the reflection spectra of the spiral antenna to a lower frequency. (credit: UNIST)

Abstract of Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.

New nuclear magnetic resonance technique offers ‘molecular window’ for live disease diagnosis

New nuclear magnetic resonance (NMR) system for molecular diagnosis (credit: University of Toronto Scarborough)

University of Toronto Scarborough researchers have developed a new “molecular window” technology based on nuclear magnetic resonance (NMR) that can look inside a living system to get a high-resolution profile of which specific molecules are present, and extract a full metabolic profile.

“Getting a sense of which molecules are in a tissue sample is important if you want to know if it’s cancerous, or if you want to know if certain environmental contaminants are harming cells inside the body,” says Professor Andre Simpson, who led research in developing the new technique.*

An NMR spectrometer generates a powerful magnetic field that causes atomic nuclei to absorb and re-emit energy in distinct patterns, revealing a unique molecular signature — in this example: the chemical ethanol. (credit: adapted from the Bruker BioSpin “How NMR Works” video at

Simpson says there’s great medical potential for this new technique, since it can be adapted to work on existing magnetic resonance imaging (MRI) systems found in hospitals. “It could have implications for disease diagnosis and a deeper understanding of how important biological processes work,” by targeting specific biomarker molecules that are unique to specific diseased tissue.

The new approach could detect these signatures without resorting to surgery and could determine, for example, whether a growth is cancerous or benign directly from the MRI alone.

The technique could also provide highly detailed information on how the brain works, revealing the actual chemicals involved in a particular response. “It could mark an important step in unraveling the biochemistry of the brain,” says Simpson.

Overcoming magnetic distortion

Until now, traditional NMR techniques haven’t been able to provide high-resolution profiles of living organisms because of magnetic distortions from the tissue itself.  Simpson and his team were able to overcome this problem by creating tiny communication channels based on “long-range dipole interactions” between molecules.

The next step for the research is to test it on human tissue samples, says Simpson. Since the technique detects all cellular metabolites (substances such as glucose) equally, there’s also potential for non-targeted discovery.

“Since you can see metabolites in a sample that you weren’t able to see before, you can now identify molecules that may indicate there’s a problem,” he explains. “You can then determine whether you need further testing or surgery. So the potential for this technique is truly exciting.”

The research results are published in the journal Angewandte Chemie.

* Simpson has been working on perfecting the technique for more than three years with colleagues at Bruker BioSpin, a scientific instruments company that specializes in developing NMR technology. The technique, called “in-phase intermolecular single quantum coherence” (IP-iSQC), is based on some unexpected scientific concepts that were discovered in 1995, which at the time were described as impossible and “crazed” by many researchers. The technique developed by Simpson and his team builds upon these early discoveries. The work was supported by Mark Krembil of the Krembil Foundation and the Natural Sciences Engineering Research Council of Canada (NSERC).

Abstract of In-Phase Ultra High-Resolution In Vivo NMR

Although current NMR techniques allow organisms to be studied in vivo, magnetic susceptibility distortions, which arise from inhomogeneous distributions of chemical moieties, prevent the acquisition of high-resolution NMR spectra. Intermolecular single quantum coherence (iSQC) is a technique that breaks the sample’s spatial isotropy to form long range dipolar couplings, which can be exploited to extract chemical shift information free of perturbations. While this approach holds vast potential, present practical limitations include radiation damping, relaxation losses, and non-phase sensitive data. Herein, these drawbacks are addressed, and a new technique termed in-phase iSQC (IP-iSQC) is introduced. When applied to a living system, high-resolution NMR spectra, nearly identical to a buffer extract, are obtained. The ability to look inside an organism and extract a high-resolution metabolic profile is profound and should find applications in fields in which metabolism or in vivo processes are of interest.

Travelers to Mars risk leukemia cancer, weakened immune function from radiation, NASA-funded study finds

The spleen from a mouse exposed to a mission-relevant dose (20 cGy, 1 GeV/n) of iron ions (bottom) was ~ 30 times the normal volume compared with the spleen from a control mouse (top). (credit: C Rodman et al./Leukemia)

Radiation encountered in deep space travel may increase the risk of leukemia cancer in humans traveling to Mars, NASA-funded researchers at the Wake Forest Institute for Regenerative Medicine and colleagues have found, using mice transplanted with human stem cells.

“Our results are troubling because they show radiation exposure could potentially increase the risk of leukemia,” said Christopher Porada, Ph.D., associate professor of regenerative medicine and senior researcher on the project.

Radiation exposure is believed to be one of the most dangerous aspects of traveling to Mars, according to NASA. The average distance to Mars is 140 million miles, and a round trip could take three years.

The goal of the study, published in the journal Leukemia, was to assess the direct effects of simulated solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation on human hematopoietic stem cells (HSCs). These stem cells comprise less than 0.1% of the bone marrow of adults, but produce the many types of blood cells that circulate through the body and work to transport oxygen, fight infection, and eliminate any malignant cells that arise.

For the study, human HSCs from healthy donors of typical astronaut age (30–55 years) were exposed to Mars mission-relevant doses of protons and iron ions — the same types of radiation that astronauts would be exposed to in deep space, followed by laboratory and animal studies to define the impact of the exposure.

“Radiation exposure at these levels was highly deleterious to HSC function, reducing their ability to produce almost all types of blood cells, often by 60–80 percent,” said Porada. “This could translate into a severely weakened immune system and anemia during prolonged missions in deep space.”

The radiation also caused mutations in genes involved in the hematopoietic process and dramatically reduced the ability of HSCs to give rise to mature blood cells.

Previous studies had already demonstrated that exposure to high doses of radiation, such as from X-rays, can have harmful (even life-threatening) effects on the body’s ability to make blood cells, and can significantly increase the likelihood of cancers, especially leukemias. However, the current study was the first to show a damaging effect of lower, mission-relevant doses of space radiation.

Mice develop T-cell acute lymphoblastic leukemia, weakened immune function

The next step was to assess how the cells would function in the human body. For that purpose, mice were transplanted with GCR-irradiated human HSCs, essentially “humanizing” the animals. The mice developed what appeared to be T-cell acute lymphoblastic leukemia — the first demonstration that exposure to space radiation may increase the risk of leukemia in humans.

“Our results show radiation exposure could potentially increase the risk of leukemia in two ways,” said Porada. “We found that genetic damage to HSCs directly led to leukemia. Secondly, radiation also altered the ability of HSCs to generate T and B cells, types of white blood cells involved in fighting foreign ‘invaders’ like infections or tumor cells. This may reduce the ability of the astronaut’s immune system to eliminate malignant cells that arise as a result of radiation-induced mutations.”

Porada said the findings are particularly troubling given previous work showing that conditions of weightlessness/microgravity present during spaceflight can also cause marked alterations in astronaut’s immune function, even after short duration missions in low-earth orbit, where they are largely protected from cosmic radiation.

Taken together, the results indicate that the combined exposure to microgravity and SEP/GCR radiation that would occur during extended deep space missions, such as to Mars, could potentially exacerbate the risk of immune-dysfunction and cancer,

NASA’s Human Research Program is also exploring conditions of microgravity, isolation and confinement, hostile and closed environments, and distance from Earth. The ultimate goal of the research is to make space missions as safe as possible.

Researchers at Wake Forest Baptist Medical Center, Brookhaven National Laboratory, and the University of California Davis Comprehensive Cancer Center were also involved in the study.

Abstract of In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Scientists reverse aging in mice by repairing damaged DNA

A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.

In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.

The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.

Disarming a rogue agent: When the NAD molecule (red) binds to the DBC1 protein (beige), it prevents DBC1 from attaching to and incapacitating a protein (PARP1) that is critical for DNA repair. (credit: David Sinclair)

Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”

What it means for astronauts, childhood cancer survivors, and the rest of us

The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).

The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.

The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.

For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.

Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.

Abstract of A conserved NAD+ binding pocket that regulates protein-protein interactions during aging

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.

Mayo Clinic discovers high-intensity aerobic training can reverse aging

Mayo Clinic study finds high-intensity aerobic exercise may reverse aging (credit: Flickr user Global Panorama via Creative Commons license)

A Mayo Clinic study says the best training for adults is high-intensity aerobic exercise, which they believe can reverse some cellular aspects of aging.

Mayo researchers compared 12 weeks of high-intensity interval training (workouts in which you alternate periods of high-intensity exercise with low-intensity recovery periods), resistance training, and combined training. While all three enhanced insulin sensitivity and lean mass, only high-intensity interval training and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. (Decline in mitochondrial content and function are common in older adults.)

High-intensity intervals also improved muscle protein content, which enhanced energetic functions and also caused muscle enlargement, especially in older adults. The researchers said exercise training significantly enhanced the cellular machinery responsible for making new proteins. That contributes to protein synthesis, thus reversing a major adverse effect of aging.

12 weeks exercise training in younger and older people (credit: Mayo Clinic)

“We encourage everyone to exercise regularly, but the take-home message for aging adults is that supervised high-intensity training is probably best, because, both metabolically and at the molecular level, it confers the most benefits,” says K. Sreekumaran Nair, M.D., Ph.D., a Mayo Clinic endocrinologist and senior researcher on the study.

He says the high-intensity training reversed some manifestations of aging in the body’s protein function, but noted that increasing muscle strength requires resistance training a couple of days a week.

Other findings

In the study, researchers tracked metabolic and molecular changes in a group of young and older adults over 12 weeks, gathering data 72 hours after individuals in randomized groups completed each type of exercise. General findings showed:

  • Cardio respiratory health, muscle mass, and insulin sensitivity improved with all training.
  • Mitochondrial cellular function declined with age but improved with training.
  • Increase in muscle strength occurred only modestly with high-intensity interval training, but occurred with resistance training alone or when added to the aerobic training.
  • Exercise improves skeletal muscle gene expression independent of age.
  • Exercise substantially enhanced the ribosomal proteins responsible for synthesizing new proteins, which is mainly responsible for enhanced mitochondrial function.
  • Training has no significant effect on skeletal muscle DNA epigenetic changes but promotes skeletal muscle protein expression with maximum effect in older adults.

The research findings appear in Cell Metabolism. The research was supported by the National Institutes of Health, Mayo Clinic, the Robert and Arlene Kogod Center on Aging, and the Murdock-Dole Professorship.

Abstract of Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans

The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.

Whole-body vibration may be as effective as regular exercise

Hate treadmills? No prob. The Tranquility Pod uses “pleasant sound, gentle vibration, and soothing light to transport the body, mind, and spirit to a tranquil state of relaxation” — and maybe lose weight (and $30,000). (credit: Hammacher Schlemmer)

If you’re overweight and find it challenging to exercise regularly, now there’s good news: A less strenuous form of exercise known as whole-body vibration (WBV) can mimic the muscle and bone health benefits of regular exercise — at least in mice — according to a new study published in the Endocrine Society’s journal Endocrinology.

Lack of exercise is contributing to the obesity and diabetes epidemics, according to the researchers. These disorders can also increase the risk of bone fractures. Physical activity can help to decrease this risk and reduce the negative metabolic effects of these conditions.

But the alternative, WBV, can be experienced while sitting, standing, or even lying down on a machine with a vibrating platform. When the machine vibrates, it transmits energy to your body, and your muscles contract and relax multiple times during each second.

“Our study is the first to show that whole-body vibration may be just as effective as exercise at combating some of the negative consequences of obesity and diabetes,” said the study’s first author, Meghan E. McGee-Lawrence, Ph.D., of Augusta University in Georgia. “While WBV did not fully address the defects in bone mass of the obese mice in our study, it did increase global bone formation, suggesting longer-term treatments could hold promise for preventing bone loss as well.”

Just as effective as a treadmill

Glucose and insulin tolerance testing revealed that the genetically obese and diabetic mice showed similar metabolic benefits from both WBV and exercising on a treadmill. Obese mice gained less weight after exercise or WBV than obese mice in the sedentary group, although they remained heavier than normal mice. Exercise and WBV also enhanced muscle mass and insulin sensitivity in the genetically obese mice.

The findings suggest that WBV may be a useful supplemental therapy to combat metabolic dysfunction in individuals with morbid obesity. “These results are encouraging,” McGee-Lawrence said. “However, because our study was conducted in mice, this idea needs to be rigorously tested in humans to see if the results would be applicable to people.”

The authors included researchers at the National Institute of Health’s National Institute of Aging (NIA). Funding was provided by the American Diabetes Association, the National Institutes of Health’s National Institute of Diabetes and Digestive Kidney Diseases, and the National Institute on Aging.

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* To conduct the study, researchers examined two groups of 5-week-old male mice. One group consisted of normal mice, while the other group was genetically unresponsive to the hormone leptin, which promotes feelings of fullness after eating. Mice from each group were assigned to sedentary, WBV or treadmill exercise conditions.

After a week-long period to grow used to the exercise equipment, the groups of mice began a 12-week exercise program. The mice in the WBV group underwent 20 minutes of WBV at a frequency of 32 Hz with 0.5g acceleration each day. Mice in the treadmill group walked for 45 minutes daily at a slight incline. For comparison, the third group did not exercise. Mice were weighed weekly during the study.

Abstract of Whole-body vibration mimics the metabolic effects of exercise in male leptin receptor deficient mice

Whole-body vibration has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether whole-body vibration recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wildtype (Wt) and leptin receptor deficient (db/db) mice to daily treadmill exercise or whole-body vibration for three months. Body weights were analyzed and compared with Wt and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following treadmill exercise or whole-body vibration. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. Treadmill exercise and whole-body vibration also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and whole-body vibration increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that whole-body vibration recapitulates the effects of exercise on metabolism in type 2 diabetes.

First nanoengineered retinal implant could help the blind regain functional vision

Activated by incident light, photosensitive silicon nanowires 1 micrometer in diameter stimulate residual undamaged retinal cells to induce visual sensations. (credit (image adapted): Sohmyung Ha et al./ J. Neural Eng)

A team of engineers at the University of California San Diego and La Jolla-based startup Nanovision Biosciences Inc. have developed the first nanoengineered retinal prosthesis — a step closer to restoring the ability of neurons in the retina to respond to light.

The technology could help tens of millions of people worldwide suffering from neurodegenerative diseases that affect eyesight, including macular degeneration, retinitis pigmentosa, and loss of vision due to diabetes.

Despite advances in the development of retinal prostheses over the past two decades, the performance of devices currently on the market to help the blind regain functional vision is still severely limited — well under the acuity threshold of 20/200 that defines legal blindness.

The new prosthesis relies on two new technologies: implanted arrays of photosensitive nanowires and a wireless power/data system.

Implanted arrays of silicon nanowires

The new prosthesis uses arrays of nanowires that simultaneously sense light and electrically stimulate the retina. The nanowires provide higher resolution than anything achieved by other devices — closer to the dense spacing of photoreceptors in the human retina, according to the researchers.*

Comparison of retina and electrode geometries between an existing retinal prosthesis and new nanoengineered prosthesis design. (left) Planar platinum electrodes (gray) of the FDA-approved Argus II retinal prosthesis (a 60-element array with 200 micrometer electrode diameter). (center) Retinal photoreceptor cells: rods (yellow) and cones (green). (right) Fabricated silicon nanowires (1 micrometer in diameter) at the same spatial magnification as photoreceptor cells. (credit: Science Photo Library and Sohmyung Ha et al./ J. Neural Eng.)

Existing retinal prostheses require a vision sensor (such as a camera) outside of the eye to capture a visual scene and then transform it into signals to sequentially stimulate retinal neurons (in a matrix). Instead, the silicon nanowires mimic the retina’s light-sensing cones and rods to directly stimulate retinal cells. The nanowires are bundled into a grid of electrodes, directly activated by light.

This direct, local translation of incident light into electrical stimulation makes for a much simpler — and scalable — architecture for a prosthesis, according to the researchers.

Wireless power and telemetry system

For the new device, power is delivered wirelessly, from outside the body to the implant, through an inductive powering telemetry system. Data to the nanowires is sent over the same wireless link at record speed and energy efficiency. The telemetry system is capable of transmitting both power and data over a single pair of inductive coils, one emitting from outside the body, and another on the receiving side in the eye.**

Three of the researchers have co-founded La Jolla-based Nanovision Biosciences, a partner in this study, to further develop and translate the technology into clinical use, with the goal of restoring functional vision in patients with severe retinal degeneration. Animal tests with the device are in progress, with clinical trials following.***

The research was described in a recent issue of the Journal of Neural Engineering. It was funded by Nanovision Biosciences, Qualcomm Inc., and the Institute of Engineering in Medicine and the Clinical and Translational Research Institute at UC San Diego.

* For visual acuity of 20/20,  an electrode pixel size of 5 μm (micrometers) is required; 20/200 visual acuity requires 50 μm. The minimum number of electrodes required for pattern recognition or reading text is estimated to be about 600. The new nanoengineered silicon nanowire electrodes are 1 μm in diameter, and for the experiment, 2500 silicon nanowires were used.

** The device is highly energy efficient because it minimizes energy losses in wireless power and data transmission and in the stimulation process, recycling electrostatic energy circulating within the inductive resonant tank, and between capacitance on the electrodes and the resonant tank. Up to 90 percent of the energy transmitted is actually delivered and used for stimulation, which means less RF wireless power emitting radiation in the transmission, and less heating of the surrounding tissue from dissipated power.

These are primary cortical neurons cultured on the surface of an array of optoelectronic nanowires. Here a neuron is pulling the nanowires, indicating the the cell is doing well on this material. (credit: UC San Diego)

*** For proof-of-concept, the researchers inserted the wirelessly powered nanowire array beneath a transgenic rat retina with rhodopsin P23H knock-in retinal degeneration. The degenerated retina interfaced in vitro with a microelectrode array for recording extracellular neural action potentials (electrical “spikes” from neural activity).

Abstract of Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry

Objective. Despite considerable advances in retinal prostheses over the last two decades, the resolution of restored vision has remained severely limited, well below the 20/200 acuity threshold of blindness. Towards drastic improvements in spatial resolution, we present a scalable architecture for retinal prostheses in which each stimulation electrode is directly activated by incident light and powered by a common voltage pulse transferred over a single wireless inductive link. Approach. The hybrid optical addressability and electronic powering scheme provides separate spatial and temporal control over stimulation, and further provides optoelectronic gain for substantially lower light intensity thresholds than other optically addressed retinal prostheses using passive microphotodiode arrays. The architecture permits the use of high-density electrode arrays with ultra-high photosensitive silicon nanowires, obviating the need for excessive wiring and high-throughput data telemetry. Instead, the single inductive link drives the entire array of electrodes through two wires and provides external control over waveform parameters for common voltage stimulation. Main results. A complete system comprising inductive telemetry link, stimulation pulse demodulator, charge-balancing series capacitor, and nanowire-based electrode device is integrated and validated ex vivo on rat retina tissue. Significance. Measurements demonstrate control over retinal neural activity both by light and electrical bias, validating the feasibility of the proposed architecture and its system components as an important first step towards a high-resolution optically addressed retinal prosthesis.