If the results hold up in people, they could lead to an entirely new way to treat aging, says gerontology and cancer researcher Norman Sharpless at the University of North Carolina School of Medicine in Chapel Hill. Most prospective antiaging treatments would require people to take a drug for decades. Periodically zapping senescent cells might temporarily turn back the clock and improve health for people who are already aging, he says. “If this paper is right, I believe it will be one of the most important aging papers ever,” Sharpless says.
Senescent cells are ones that have ceased to divide and do their usual jobs. Instead, they hunker down and pump out inflammatory chemicals that may damage surrounding tissues and promote further aging. “They’re zombie cells,” says Steven Austad, a biogerontologist at the University of Alabama at Birmingham. ”They’ve outlived their usefulness. They’re bad.”
Cancer biologist Jan van Deursen of the Mayo Clinic in Rochester, Minn., and colleagues devised the strategy for eliminating senescent cells by making the cells commit suicide. A protein called p16 builds up in senescent cells, the researchers had previously discovered. The team hooked up a gene for a protein that causes cells to kill themselves to DNA that helps turn on p16 production, so that whenever p16 was made the suicide protein was also made.
The paper appears in Nature (behind their paywall)
Darren J. Baker, Bennett G. Childs, Matej Durik, Melinde E. Wijers, Cynthia J. Sieben, Jian Zhong, Rachel A. Saltness, Karthik B. Jeganathan, Grace Casaclang Verzosa, Abdulmohammad Pezeshki, Khashayarsha Khazaie, Jordan D. Miller & Jan M. van Deursen
Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16Ink4a (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.
Exercise is extremely healthy and should be pursued for reasons other than weight loss.
Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans
Herman Pontzer, Ramon Durazo-Arvizu, Lara R. Dugas, Jacob Plange-Rhule, Pascal Bovet, Terrence E. Forrester, Estelle V. Lambert, Richard S. Cooper, Dale A. Schoeller, Amy Luke
•We measured total energy expenditure and physical activity in a large adult sample •Above moderate activity levels, total energy expenditure plateaued •Body fat percentage was positively related to total energy expenditure •Activity intensity was inversely related to total energy expenditure
Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [ 1–3 ]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [ 4 ] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [ 5–8 ]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [ 9 ]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [ 1–3 ] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.
Howard Eichenbaum, a neuroscientist at Boston University, and collaborators showed that cells in rats that form the brain’s internal GPS system, known as grid cells, are more malleable than had been anticipated. Typically these cells act like a dead-reckoning system, with certain neurons firing when an animal is in a specific place. (The researchers who discovered this shared the Nobel Prize in 2014.) Eichenbaum found that when an animal is kept in place — such as when it runs on a treadmill — the cells keep track of both distance and time. The work suggests that the brain’s sense of space and time are intertwined.
The findings help to broaden our understanding of how the brain’s memory and navigation systems work. Perhaps both grid cells and other GPS-like cells aren’t tuned only to space but are capable of encoding any relevant property: time, smell or even taste. “It probably points to a broad thing the hippocampus does,” said Loren Frank, a neuroscientist at the University of California, San Francisco, who studies memory and the hippocampus. “It figures out the relevant axis for encoding experiences and then uses the cells to map those experiences.”
Buzsáki points out that it may not even make sense to think of hippocampal cells as independently coding for space or time. The human brain often considers time and distance interchangeably. “If one asks how far New York is from LA, the answers you get vary: 3,000 miles, six hours by flight,” he said. “In older language, distances were typically given by time — the days it takes to go from one valley to another — since it was not distance but the number of sunsets that was easy to calculate.”
For Buzsáki, the issue goes beyond neuroscience and reaches into physics. Physicists consider space-time as a cohesive, four-dimensional entity, a fabric upon which the objects and events of the universe are embedded. “Neuroscience must converge back to the old problem of physics: Are there place and time cells? Or is there only a single time-space-continuum representation in the brain?” Buzsáki said.
During Running in Place, Grid Cells Integrate Elapsed Time and Distance Run
Benjamin J. Kraus, Mark P. Brandon, Robert J. Robinson II, Michael A. Connerney, Michael E. Hasselmo, Howard Eichenbaum
•Time and distance coding by grid cells can be studied in rats running in place •In this task, grid cell activity reflects a combination of time and distance coding •Grid cells are more sharply tuned to time and distance than non-grid cells •Many grid cells exhibit multiple time and distance fields
The spatial scale of grid cells may be provided by self-generated motion information or by external sensory information from environmental cues. To determine whether grid cell activity reflects distance traveled or elapsed time independent of external information, we recorded grid cells as animals ran in place on a treadmill. Grid cell activity was only weakly influenced by location, but most grid cells and other neurons recorded from the same electrodes strongly signaled a combination of distance and time, with some signaling only distance or time. Grid cells were more sharply tuned to time and distance than non-grid cells. Many grid cells exhibited multiple firing fields during treadmill running, parallel to the periodic firing fields observed in open fields, suggesting a common mode of information processing. These observations indicate that, in the absence of external dynamic cues, grid cells integrate self-generated distance and time information to encode a representation of experience.
Just how do you navigate in open waters without a compass when it is cloudy? Sunstones have been proposed. In theory you can use polarization of the available light and combine that information with a sundial to figure out where the Sun is.
Several researchers have tried to duplicate this over the years with poor results. Another attempt appear in the Royal Society Open Science journal. They find it is sort of possible with very clear cordierite crystals with tourmaline crystals being the next choice. It is still very iffy.
Adjustment errors of sunstones in the rst step of sky-polarimetric Viking navigation: studies with dichroic cordierite/ tourmaline and birefringent calcite crystals
Dénes Száz1, Alexandra Farkas1,2, Miklós Blahó1, András Barta1,3, Ádám Egri1,2,3, Balázs Kretzer1, Tibor Hegedüs4, Zoltán Jäger4 and Gábor Horváth1
1Environmental Optics Laboratory, Department of Biological Physics, Physical Institute, Eötvös University, Pázmány sétány 1, Budapest 1117, Hungary 2 Danube Research Institute, MTA Centre for Ecological Research, Karolina út 29–31, Budapest 1113, Hungary 3Estrato Research and Development Ltd, Nemetvolgyi ut 91/c, Budapest 1124, Hungary 4Astronomical Observatory of Baja, University of Szeged, Pf. 766, Baja 6500, Hungary
According to an old but still unproven theory, Viking navigators analysed the skylight polarization with dichroic cordierite or tourmaline, or birefringent calcite sunstones in cloudy/foggy weather. Combining these sunstones with their sun-dial, they could determine the position of the occluded sun, from which the geographical northern direction could be guessed. In psychophysical laboratory experiments, we studied the accuracy of the first step of this sky-polarimetric Viking navigation. We measured the adjustment error e of rotatable cordierite, tourmaline and calcite crystals when the task was to determine the direction of polarization of white light as a function of the degree of linear polarization p. From the obtained error functions e(p), the thresholds p* above which the first step can still function (i.e. when the intensity change seen through the rotating analyser can be sensed) were derived. Cordierite is about twice as reliable as tourmaline. Calcite sunstones have smaller adjustment errors if the navigator looks for that orientation of the crystal where the intensity difference between the two spots seen in the crystal is maximal, rather than minimal. For higher p (greater than pcrit) of incident light, the adjustment errors of calcite are larger than those of the dichroic cordierite (pcrit=20%) and tourmaline (pcrit=45%), while for lower p (less than pcrit) calcite usually has lower adjustment errors than dichroic sunstones. We showed that real calcite crystals are not as ideal sunstones as it was believed earlier, because they usually contain scratches, impurities and crystal defects which increase considerably their adjustment errors. Thus, cordierite and tourmaline can also be at least as good sunstones as calcite. Using the psychophysical e(p) functions and the patterns of the degree of skylight polarization measured by full-sky imaging polarimetry, we computed how accurately the northern direction can be determined with the use of the Viking sun-dial under 10 different sky conditions at 61° latitude, which was one of the main Viking sailing routes. According to our expermiments, under clear skies, using calcite or cordierite or tourmaline sunstones, Viking sailors could navigate with net orientation errors |Σmax|≤3°. Under overcast conditions, their net navigation error depends on the sunstone type: |Σmax(calcite)|≤6° , |Σmax(cordierite)|≤10° and |Σmax(tourmaline)|≤17°∘
While you can measure the energy content of food understanding how a specific metabolism handles specific foods and measuring what a person eats are inexact. It can be useful if it enforces mindful eating, but something better is needed. An excellent post in Mosaic from an episode of the Gastropod podcast.