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Oxidized, damaged and misfolded proteins accumulate during aging and contribute to impaired cell function and tissue homeodynamics. Damaged proteins are degraded by cellular clearance mechanisms like the 20S proteasome. Aging relates to low 20S proteasome function, whereas long-lived species show high levels. However, contradictory results exist depending on the tissue or cell type and it is unknown how the 20S proteasome functions in exceptionally old mice. The aim of this study was to investigate two proteasome activities (caspase-like and chymotrypsin-like) in several tissues (lung, heart, axillary lymph nodes, liver, kidney) and cells (peritoneal leukocytes) from adult (28 ± 4 weeks, n = 12), old (76 ± 4 weeks, n = 9) and exceptionally old (128 ± 4 weeks, n = 9) BALB/c female mice. The results show different age-related changes depending on the tissue and the activity considered, so there is no universal decline in proteasome function with age in female mice. Interestingly, exceptionally old mice displayed better maintained proteasome activities, suggesting that preserved 20S proteasome is associated with successful aging.

The synthesis of amphiphilic polymer-modified graphene oxide and its evaluation in the preparation of polystyrene nanocomposites via aqueous phase emulsion polymerization have been studied. The polymer modification was achieved via surface initiated atom transfer radical polymerization (SI-ATRP) from graphene oxide and subsequent sulphonation of the resulting brush-like polymer. Fluorimetric studies using pyrene as fluorescent probe gave a critical aggregation concentration (CAC) value of 1.29 mg/ml, comparable to that of polymeric surfactants. The surfactant was evaluated in the emulsion polymerization of styrene and on increasing the surfactant concentration from 0.5 to 2.0 wt%, the nanocomposite particle size varied from 160 to 220 nm, respectively. Nanocomposite films containing amphiphilic polymer-modified graphene surfactant show lower glass transition temperature and improved thermomechanical properties. The water contact angle of the film coated on a glass substrate increased from 84° to 124°, indicating a synergistic effect of graphene and the grafted polymer, suggesting that it was use as multifunctional additive for polymer nanocomposites.

Curcumin is shown to commonly induce biphasic dose responses in a broad range of cell types, with particular emphasis on neural cells, including neuronal stem cells. The quantitative features of these biphasic dose responses, with respect to the magnitude and width of the low dose stimulation, are similar to those reported for hormetic dose responses. These hormetic dose responses occur within the framework of direct stimulatory responses as well as in preconditioning experimental protocols, displaying acquired resistance within an adaptive homeodynamic framework. These findings have important implications for study design strategies involving dose selection and spacing, as well as sample size and statistical power considerations. These findings further reflect the broadly general occurrence of hormetic dose responses that consistently appear to be independent of biological model, endpoint, inducing agent and mechanism.

The densely populated Bay of Bengal (BoB) rim witnesses the deadliest tropical cyclones (TCs) globally, before and after the summer monsoon. Previous studies indicated that enhanced salinity and reduced thermal stratification reduce cooling under BoB TCs after the monsoon, suggesting that air-sea coupling may favor stronger TCs during that season. Using observations and simulations from a one fourth degree regional ocean-atmosphere model, we show that BoB TCs are stronger before the monsoon due to a more favorable large-scale background state (less vertical wind shear and higher sea surface temperature). Air-sea coupling however alleviates this background state influence, by reducing the number of premonsoon intense TCs, because of larger cooling and reduced upward enthalpy fluxes below TCs during that season. As the impact of air-sea interactions on BoB TCs is largest for intense TCs, it should be further investigated for Category 3 and above TCs, which are not reproduced at one fourth degree resolution.

Understanding the phenomenon of health is crucial for ageing research since there is often an implicit view on what constitutes health and how to measure it. We provide some reflections on how we might better understand and measure health, discuss the basic biological principles of survival, ageing, age-related diseases and eventual death, and end by tying these ideas together to rethink the nature of and implications for healthy ageing. We defend a more positive view on health understood in terms of various phenotypic parameters, such as robustness and resilience, and show how it relates to the aim to support these parameters over time to achieve healthy ageing. Together, these ideas suggest that the most effective strategies for healthy ageing may come from the outside-in by altering those aspects of the environment that prevent robust and resilient phenotypic responses and by supporting those aspects which ensure such responses.

Evolutionary processes have developed in all organisms the intrinsic ability to counteract physiological and environmental stress as an essential tool for survival. The widely observed phenomenon, that a single or repeated exposure to mild stress can improve their biological performance and stress resistance including tolerance to severe stress, necessitates understanding the molecular mechanisms that underlie such effect. The focus of this chapter is to discuss the primary biochemical pathways that participate in stress response (SR), and form the basis of preconditioning and physiological hormesis. SR pathways are activated by a variety of stressors, such as intracellular denatured proteins, heat shock, free radicals, food deprivation, energy depletion, DNA lesions, inflammation-inducing pathogens/allergens, and unfolded proteins in the endoplasmic reticulum. Although SR pathways are generally stressor specific, different responses can be triggered depending on other factors, such as the time lapsed after stress exposure and the activation of further molecular responses by downstream modulators.

One of the aims of the EU-funded Research and Innovation Action (RIA), titled "Ageing with Elegans" (AwE) is to enhance better understanding of the factors causing health and disease in aging and develop evidence-based preventive, diagnostic, therapeutic, and other strategies. The work package-5 of this project is focused on testing the effects of phytochemicals of natural and synthetic origin on aging, longevity, and health of human cells in vitro, after the initial screening using the animal model systems of nematodes and rats and mice. Accordingly, the first series of three compounds, rosmarinic acid (ROSM), ampelopsin (AMPEL), and amorfrutin-A (AMOR), were selected to test for their short-term and long-term effects on human skin fibroblasts undergoing aging and senescence in vitro. The lifelong modulatory effects of these compounds were tested individually at two doses (0.5 and 1.0 mu M), selected after a short-term dose response check of a 20,000-fold range (0.01-200 mu M). The results show that these compounds do have some beneficial effects in terms of supporting the long-term lifelong growth and enhanced stress tolerance of serially passaged cells. These effects seem to be achieved by reducing the extent of loss of telomeres, of 5-methyl-cytosine (5-mC) and of 5-hydroxymethyl-cytosine (5-hmC), by reducing the accumulation of oxidative DNA damage product 8-OHdG. There is also some indication that these compounds induce at least one of the stress responses in terms of the increased synthesis of heat shock protein Hsp70. Thus, these phytochemicals may be potential hormetins, which bring about their health beneficial effects by the phenomenon of mild stress-induced hormesis.

Nanodiamonds (ND) and silica nanoparticles (SiO2-NP) have been much investigated for their toxicity at high doses, little is known about their biological activity at low concentrations. Here we report the biphasic dose response of ND and SiO2-NP in modulating normal human facial skin fibroblasts (FSF1) in culture. ND and SiO2-NP at low concentration (up to 0.5 μg/ml) had beneficial effects on FSF1 in terms of increasing their proliferation and metabolic activity. Exposure of FSF1 cells to low levels of NP enhanced their wound healing ability in vitro and slowed down aging during serial passaging as measured by maintenance of youthful morphology, reduction in the rate of loss of telomeres, and the over all proliferative characterisitics. Furthermore, NP treatment induced the activation of Nrf2- and FOXO3A mediated cellular stress responses, including an increased expression of heme oxygenease HO-1), sirtuin (SIRT1), and DNA methyltransferase II (DNMT2). These results imply that ND and SiO2-NP at low doses are potential hormetins, which exert mild stress-induced beneficial hormetic effects through improved survival, longevity, maintenance, repair andfunction of human cells

Biogerontology is the study of the biological basis of ageing and age-related diseases. The phenomenon and the process of ageing are well understood in evolutionary and biological terms; and a conceptual framework has been established within which general principles of ageing and longevity can be formulated. The phenotype of ageing in terms of progressive loss of physical function and fitness is best seen during the period of survival after the evolution-determined essential lifespan (ELS) of a species. However, the ageing phenotype is highly heterogenous and individualistic at all levels from the whole body to the molecular one. Most significantly, the process and the progression of ageing are not determined by any specific gerontogenes. Ageing is the result of imperfect maintenance and repair systems that allow a progressive shrinkage of the homeodynamic space of an individual. The challenge is to develop and apply wholistic approaches to the complex trait of ageing for maintaining and/or improving health. One such approach is that of mild stress-induced physiological hormesis by physical, mental and nutritional hormetins. Biogerontological research offers numerous opportunities for developing evidence-based novel biomedical technologies for maintaining and improving health, for preventing the onset of age-related diseases, and for extending the health-span. (www.actabiomedica.it)