Global S&T Development Trend Analysis Platform of Resources and Environment
It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated(1-6). Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan(4,7). Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases(8,9) shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer'
Two epigenetic regulators-identified in an RNA interference screen in Caenhorhabditis elegans, and conserved in mammals-diminish mitochondrial function and accelerate the age-related deterioration of behaviour.
High-pressure diamond anvil cell experiments reveal that compression strengthening of nanocrystalline nickel increases as its grain sizes decrease to 3 nanometres, owing to dislocation hardening and suppression of grain boundary plasticity.
The Hall-Petch relationship, according to which the strength of a metal increases as the grain size decreases, has been reported to break down at a critical grain size of around 10 to 15 nanometres(1,2). As the grain size decreases beyond this point, the dominant mechanism of deformation switches from a dislocation-mediated process to grain boundary sliding, leading to material softening. In one previous approach, stabilization of grain boundaries through relaxation and molybdenum segregation was used to prevent this softening effect in nickel-molybdenum alloys with grain sizes below 10 nanometres(3). Here we track in situ the yield stress and deformation texturing of pure nickel samples of various average grain sizes using a diamond anvil cell coupled with radial X-ray diffraction. Our high-pressure experiments reveal continuous strengthening in samples with grain sizes from 200 nanometres down to 3 nanometres, with the strengthening enhanced (rather than reduced) at grain sizes smaller than 20 nanometres. We achieve a yield strength of approximately 4.2 gigapascals in our 3-nanometre-grain-size samples, ten times stronger than that of a commercial nickel material. A maximum flow stress of 10.2 gigapascals is obtained in nickel of grain size 3 nanometres for the pressure range studied here. We see similar patterns of compression strengthening in gold and palladium samples down to the smallest grain sizes. Simulations and transmission electron microscopy reveal that the high strength observed in nickel of grain size 3 nanometres is caused by the superposition of strengthening mechanisms: both partial and full dislocation hardening plus suppression of grain boundary plasticity. These insights contribute to the ongoing search for ultrastrong metals via materials engineering.
