Caloric Restriction Mimetics Attenuate the Hallmarks of Aging

Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We found that there are at least 4 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the stimulation cytosolic AcCoA consumption, (iii) the inhibition of protein acetyltransferases, or (iii) the stimulation of protein deacetylases. Thus, AcCoA depleting agents, AcCoA-consuming agents, acetyltransferase inhibitors or deacetylase activators are highly efficient inducers of autophagy and reduce aging-associated diseases including diabetes, obesity, cardiac failure and failing cancer immunosurveillance. Hence, we classify them as “caloric restriction mimetics” (CRM). We have initiated the systematic search for CRMs based on their cellular effects in vitro. We built screening assays amenable to high-throughput technology for the identification of CRMs. These results will be discussed.

When Yeast Cells Change their Mind: Cell Cycle 'Start' is Reversible under Starvation

Eukaryotic cells decide in late G1 whether to commit to another round of genome duplication and division. This point of irreversible cell cycle commitment is a molecular switch termed 'Restriction Point' in mammals and 'Start' in budding yeast. At Start, yeast cells integrate multiple signals such as pheromones, osmolarity, and nutrients. If sufficient nutrients are lacking, cells will not pass Start. However, how the cells respond to nutrient depletion after they have made the Start decision, remains poorly understood. Here, we analyze by live cell imaging how post-Start yeast cells respond to nutrient depletion. We monitor fluorescently labelled Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 back into the nucleus. This occurs when cells are faced with starvation up to 20 minutes after Start. In these cells, the positive feedback loop is interrupted, Whi5 re-binds DNA, and CDK activation occurs a second time once nutrients are replenished. Cells which re-import Whi5 also become sensitive to mating pheromone again, and thus behave like pre-Start cells. In summary, we show that upon starvation the commitment decision at Start can be reversed. We therefore propose that in yeast, as has been suggested for mammalian cells, cell cycle commitment is a multi-step process, where irreversibility in face of nutrient signaling is only reached approximately 20 minutes after CDK activation at Start.

Cellular Self-Digestion and Persistence in Bacteria

Cellular self-digestion is an evolutionarily conserved process occurring in prokaryotic cells that enables survival under stressful conditions by recycling essential energy molecules. Self-digestion, which is triggered by extracellular stress conditions, such as nutrient depletion and overpopulation, induces degradation of intracellular components. This self-inflicted damage renders the bacterium less fit to produce building blocks and resume growth upon exposure to fresh nutrients. However, self-digestion may also provide temporary protection from antibiotics until the self-digestion-mediated damage is repaired. In fact, many persistence mechanisms identified to date may be directly or indirectly related to self-digestion, as these processes are also mediated by many degradative enzymes, including proteases and ribonucleases (RNases). In this review article, we will discuss the potential roles of self-digestion in bacterial persistence.

Phytoplankton biodiversity and the inverted paradox

Earth’s aquatic food webs are overwhelmingly supported by planktonic microalgae that live in the sunlit water column where only a minimum number of physical niches are readily identifiable. Despite this paucity of environmental differentiation, these “phytoplankton” populations exhibit a rich biodiversity, an observation not easily reconciled with broadly accepted rules of resource-based competitive exclusion. This conundrum is referred to as the “Paradox of the Plankton”. Consideration of physical distancing between nutrient depletion zones around individual phytoplankton, however, suggests a competition-neutral resource landscape. Application of neutral theory to the sheer number of phytoplankton in physically-mixed water masses yields a prediction of astronomical biodiversity, suggesting the inverted paradox: Why are there so few phytoplankton species? Here, we introduce a trophic constraint on phytoplankton that, when combined with stochastic principals of ecological drift, predicts only modest levels of diversity in an otherwise competition-neutral landscape. Our “trophic exclusion” principle predicts diversity to be independent of population size and yields a species richness across cell-size classes that is consistent with broad oceanographic survey observations.

Addressing Nutrient Depletion in Tanzanian Sisal Fiber Production Using Life Cycle Assessment and Circular Economy Principles, with Bioenergy Co-Production

Nutrient depletion in Tanzanian sisal production has led to yield decreases over time. We use nutrient mass balances embedded within a life cycle assessment to quantify the extent of nutrient depletion for different production systems, and then used circular economy principles to identify potential cosubstrates from within the Tanzanian economy to anaerobically digest with sisal wastes. The biogas produced was then used to generate bioelectricity and the digestate residual can be used as a fertilizer to address the nutrient depletion. Life cycle assessment was used in a gate-to-gate assessment of the anaerobic digestion options with different cosubstrates. If no current beneficial use of the cosubstrate was assumed, then beef manure and marine fish processing waste were the best cosubstrates. If agricultural wastes were assumed to have a current beneficial use as fertilizer, then marine fish processing waste and human urine were the best cosubstrates. The largest reduction in environmental impacts resulted from bioelectricity replacing electricity from fossil fuels in the national electricity grid and improved onsite waste management practices. There is significant potential to revitalize Tanzanian sisal production by applying circular economy principles to sisal waste management to address soil nutrient depletion and co-produce bioenergy.

Using Life Cycle Assessment and Circular Economy Principles to Address Nutrient Depletion in Tanzanian Sisal Fibre Production

Nutrient depletion in Tanzanian sisal production has led to yield decreases over time. We use nutrient mass balances embedded within a life cycle assessment to quantify the extent of nutrient depletion for different production systems, then used circular economy principles to identify potential cosubstrates from within the Tanzanian economy to anaerobically digest with sisal wastes. The biogas produced is then used to generate bioelectricity and the digestate residual can be used as a fertilizer to address the nutrient depletion. If no current beneficial use of the cosubstrate was assumed, then beef manure and marine fish processing waste were the best cosubstrates. If agricultural wastes were assumed to have a current beneficial use as fertilizer, then marine fish processing waste and human urine were the best cosubstrates. The largest reduction in environmental impacts resulted from bioelectricity replacing electricity from fossil fuels in the national electricity grid and improved onsite waste management practices. There is significant potential to revitalize Tanzanian sisal production by applying circular economy principles to sisal waste management and bioenergy production.

Effects of Sowing Dates and Weed Management on Weed Growth and Nutrients Depletion by Weeds and Uptake by Wheat (Triticum Aestivum L.) Under Shiwalik Foothills Plains of Jammu

A field experiment was conducted to study the effect of sowing dates and weed management practices on weed growth and nutrients depletion by weeds and uptake by wheat. The results revealed that crop sown on 15th November significantly reduced the weed density and its dry matter was compared to crop sown on 25th December. Among weed management treatments, ready mix application of sulfosulfuron + metsulfuron at 30 g/ha + 2 g/ha followed by metribuzin (210 g/ha) showed significantly lowest density and dry weight of weeds. Wheat crop sown on 15th November showed significantly lowest nutrient depletion by weeds and highest yield, nutrients uptake by wheat crop. Significantly lowest nutrient depletion by weeds, highest growth parameters, yield attributes, yield and nutrient uptake by wheat crop were recorded with the ready mix application of sulfosulfuron + metsulfuron at 30 g/ha + 2 g/ha. Regression equation revealed that unit increase in the weed control efficiency increased the grain yield by 25.56 kg/ha. Bangladesh J. Bot. 50(2): 311-318, 2021 (June)