Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naïve cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naïve T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.
Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More than 300 molecules, often complex and with unique skeletons originating from intra- and inter-molecular cyclizations, and/or rearrangements, are illustrated. The reported syntheses are mentioned. The issue of a potential microbial link to their biosynthesis is also shortly outlined.
The ascidian Aplidium conicum collected along Sardinia coasts (Italy) contained two novel prenylated benzoquinones, designated thiaplidiaquinone A (1) and thiaplidiaquinone B (2). These compounds showed an unprecedented tetracyclic structure. We have studied the pro-apototic mechanisms of both prenylated benzoquinones in the Jurkat cell line that is derived from a human T lymphoma, and we show that both compounds induce a strong production of intracellular reactive oxygen species (ROS) in this cell line. Moreover, kinetic experiments, comparing the timing of ROS induction with the collapse of the mitochondria potential (DeltaPsi(m)), clearly showed that ROS preceded the disruption of the mitochondrial potential, and the later one paralleled the appearance of apoptotic cells. Thus, thiaplidiaquinones A and B can enter into the cells and induce cell death by apoptosis.
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