Giovanni Lai

Marine-derived products are emerging for their potential in mitigating aging and age-related diseases. Among them, neurodegenerative and musculoskeletal diseases represent a major health challenge, often coexisting in older adults through interconnected biological axes. This narrative review evaluates the therapeutic potential of these chemically diverse products, integrating these two pathological domains through shared mechanisms and highlighting current experimental evidence from pre-clinical in vivo models to clinical translation toward regulatory approval. Pre-clinical evidence identified several candidates with neuroprotective, anti-sarcopenic, chondroprotective or anti-osteoporotic properties, and suggests modulation of key hallmarks of aging (e.g., mitochondrial dysfunction, proteostasis/autophagy, inflammation/senescence, and gut microbiota). A candidate pleiotropic efficacy across both disease domains was suggested for fucoidan, chitosan oligosaccharides, astaxanthin, fucoxanthin and ω-3 PUFAs. However, clinical translation remains highly limited: several marine products that, in animal models, engage disease-modifying mechanisms, fail to demonstrate disease modification in humans. Out of numerous explored products, only sodium oligomannate (GV-971) has achieved disease-specific regulatory approval for Alzheimer’s disease, but only in China, and still lacks a robust international consensus. Other compounds have either failed to replicate pre-clinical efficacy in human trials or have transitioned into commercial dietary supplements without approved therapeutic claims. Finally, translational bottlenecks hindering the clinical advancement of marine compounds were discussed. Future development should prioritize standardized formulations, mechanistic insight, aged animal models and multimorbidity-oriented trials to validate cross-domain tissue protection.

The choroid plexus (ChP) is a complex ventricular structure that forms a semi-permeable barrier between the blood and cerebrospinal fluid (CSF). It is responsible for CSF secretion and clearance, contains macrophages, and is one of the few sites within the central nervous system (CNS) where T cells are present. Additionally, the ChP plays a role in detecting peripheral inflammation, which leads to the modulation of its epithelial cell function. Despite its critical importance in maintaining brain homeostasis, the ChP is often overlooked, particularly concerning the changes it undergoes with aging, such as reduced barrier function, impaired CSF production, and altered immunosurveillance. These age-related alterations may contribute to several harmful effects, including neuroinflammation and oxidative damage, potentially predisposing individuals to neurodegenerative conditions. Although knowledge is still limited, gut dysbiosis and decreased Klotho levels—of which the ChP is one of the main sources—appear to be significant contributors to ChP impairments. This narrative review will examine the impact of age-related gut dysbiosis on the CNS, focusing on the ChP, and explore the effects of reduced Klotho levels in this brain structure. We will also propose the hypothesis that combining the administration of probiotics capable of restoring gut microbiota eubiosis with gene therapy to upregulate Klotho in the ChP could help preserve the structural and functional integrity of the aging brain. Finally, we will provide a technical overview to ensure that vectors encoding Klotho cDNA achieve maximum specificity for the ChP, thereby avoiding off-target effects. Graphical abstract

Ageing represents a main risk factor for several pathologies. Among them, cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) are predominant in the elderly population and often require prolonged use of multiple drugs due to their chronic nature and the high proportion of co-morbidities. Hence, research is constantly looking for novel, effective molecules to treat CVD and T2DM with minimal side effects. Marine active compounds, holding a great diversity of chemical structures and biological properties, represent interesting therapeutic candidates to treat these age-related diseases. This review summarizes the current state of research on marine compounds for the treatment of CVD and T2DM, from pre-clinical studies to clinical investigations and approved drugs, highlighting the potential of marine compounds in the development of new therapies, together with the limitations in translating pre-clinical results into human application.

The spreading of senescent cells’ burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.