Macroalgae stand out for their high content of dietary fiber (30–75%) that include soluble, sulfated (fucoidan, agaran, carrageenan, and ulvan) and non-sulfated (laminaran and alginate) polysaccharides. Many studies indicate that these compounds exert varied biological activities and health-promoting effects and for this reason, there is a growing interest for using them in food products. The aim of this review was to critically evaluate prebiotic properties of algal polysaccharides, i.e., their ability to exert biological activities by modulating the composition and/or diversity of gut microbiota (GM). Pre-clinical studies show that the non-sulfated alginate and laminaran are well-fermented by GM, promoting the formation of short chain fatty acids (SCFAs) including butyrate, and preventing that of harmful putrefactive compounds (NH 3 , phenol, p -cresol, indole and H 2 S). Alginate increases Bacteroides, Bifidobacterium , and Lactobacillus species while laminaran mostly stimulates Bacteroides sp. Results with sulfated polysaccharides are more questionable. Agarans are poorly fermentable but agarose-oligosaccharides exhibit an interesting prebiotic potential, increasing butyrate-producing bacteria and SCFAs. Though carrageenan-oligosaccharides are also fermented, their use is currently limited due to safety concerns. Regarding fucoidan, only one study reports SCFAs production, suggesting that it is poorly fermented. Its effect on GM does not indicate a clear pattern, making difficult to conclude whether it is beneficial or not. Notably, fucoidan impact on H 2 S production has not been evaluated, though some studies report it increases sulfate-reducing bacteria. Ulvan is badly fermented by GM and some studies show that part of its sulfate is dissimilated to H 2 S, which could affect colonic mitochondrial function. Accordingly, these results support the use of laminaran, alginate and agaro-oligosaccharides as prebiotics while more studies are necessary regarding that of fucoidan, carrageenan and ulvan. However, the realization of clinical trials is necessary to confirm such prebiotic properties in humans.

Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.

The complex physiology of eukaryotic cells requires that a variety of subcellular organelles perform unique tasks, even though they form highly dynamic communication networks. In the case of the endoplasmic reticulum (ER) and mitochondria, their functional coupling relies on the physical interaction between their membranes, mediated by domains known as mitochondria-ER contacts (MERCs). MERCs act as shuttles for calcium and lipid transfer between organelles, and for the nucleation of other subcellular processes. Of note, mounting evidence shows that they are heterogeneous structures, which display divergent behaviors depending on the cell type. Furthermore, MERCs are plastic structures that remodel according to intra- and extracellular cues, thereby adjusting the function of both organelles to the cellular needs. In consonance with this notion, the malfunction of MERCs reportedly contributes to the development of several age-related disorders. Here, we integrate current literature to describe how MERCs change, starting from undifferentiated cells, and their transit through specialization, malignant transformation (i.e., dedifferentiation), and aging/senescence. Along this journey, we will review the function of MERCs and their relevance for pivotal cell types, such as stem and cancer cells, cardiac, skeletal, and smooth myocytes, neurons, leukocytes, and hepatocytes, which intervene in the progression of chronic diseases related to age.