It is believed that postponing ageing is more effective and less expensive than the treatment of particular age-related diseases. Compounds which could delay symptoms of ageing, especially natural products present in a daily diet, are intensively studied. One of them is curcumin. It causes the elongation of the lifespan of model organisms, alleviates ageing symptoms and postpones the progression of age-related diseases in which cellular senescence is directly involved. It has been demonstrated that the elimination of senescent cells significantly improves the quality of life of mice. There is a continuous search for compounds, named senolytic drugs, that selectively eliminate senescent cells from organisms. In this paper, we endeavor to review the current knowledge about the anti-ageing role of curcumin and discuss its senolytic potential.

: Natural rewards, such as food, and sex are appetitive stimuli available for animals in their natural environment. Similarly, addictive rewards such as drugs of abuse possess strong, positive valence, but their action relies on their pharmacological properties. Nevertheless, it is believed that both of these kinds of rewards activate similar brain circuitry. The present study aimed to discover which parts of the brain process the experience of natural and addictive rewards. To holistically address this question, we used a single-cell whole-brain imaging approach to find patterns of activation for acute and prolonged sucrose and cocaine exposure. We analyzed almost 400 brain structures and created a brain-wide map of specific, c-Fos-positive neurons engaged by these rewards. Acute but not prolonged sucrose exposure triggered a massive c-Fos expression throughout the brain. Cocaine exposure on the other hand potentiated c-Fos expression with prolonged use, engaging more structures than sucrose treatment. The functional connectivity analysis unraveled an increase in brain modularity after the initial exposure to both types of rewards. This modularity was increased after repeated cocaine, but not sucrose, intake. To check whether discrepancies between the processing of both types of rewards can be found on a cellular level, we further studied the nucleus accumbens, one of the most strongly activated brain structures by both sucrose and cocaine experience. We found a high overlap between natural and addictive rewards on the level of c-Fos expression. Electrophysiological measurements of cellular correlates of synaptic plasticity revealed that natural and addictive rewards alike induce the accumulation of silent synapses. These results strengthen the hypothesis that in the nucleus accumbens drugs of abuse cause maladaptive neuronal plasticity in the circuitry that typically processes natural rewards.

Structural plasticity of dendritic spines is a fundamental mechanism of learning and memory. It depends on the release of brain-derived neurotrophic factor (BDNF) and activation of its receptor, tropomyosin receptor kinase B (TrkB). However, to bind TrkB, BDNF requires proteolytic cleavage to its mature form. Here, we demonstrate that MMP-9, an extracellular protease essential for neuronal function, plays a key role in this process. We show that, like BDNF, MMP-9 is rapidly released in response to synaptic stimulation, and its proteolytic activity, restricted to the activated spine, can be detected as early as 2 min after stimulation. Using two-photon microscopy and single-spine stimulation by glutamate uncaging, we demonstrate that MMP-9 action is important for TrkB activation and is required for structural plasticity. Furthermore, we provide evidence for a direct cleavage of proBDNF into mature BDNF by MMP-9. Our findings reveal a critical interaction between MMP-9 and BDNF through their autocrine regulation of TrkB activation and dendritic spine structural changes.

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