The steady and dramatic increase in the incidence of Alzheimer's disease (AD) and the lack of effective treatments have stimulated the search for strategies to prevent or delay its onset and/or progression. Since the diagnosis of dementia requires a number of established features that are present when the disease is fully developed, but not always in the early stages, the need for a biological marker has proven to be urgent, in terms of both diagnosis and monitoring of AD. AD has been shown to affect peripheral blood mononuclear cells (PBMCs) that are a critical component of the immune system which provide defence against infection. Although studies are continuously supplying additional data that emphasize the central role of inflammation in AD, PBMCs have not been sufficiently investigated in this context. Delineating biochemical alterations in AD blood constituents may prove valuable in identifying accessible footprints that reflect degenerative processes within the Central Nervous System (CNS). In this review, we address the role of biomarkers in AD with a focus on the notion that PBMCs may serve as a peripheral laboratory to find molecular signatures that could aid in differential diagnosis with other forms of dementia and in monitoring of disease progression.
Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spectrum of age-related modifications in the organism was shown to play a key role in the pathogenesis of sarcopenia. Not surprisingly, sarcopenia has sometimes been indicated as a syndrome stemming from the aging process, and not as univocal standalone disease. Due to the multidimensionality of sarcopenia, a single biomarker approach is not enough to explain the biology of this condition. The aim of this review is to suggest innovative and promising sarcopenia markers investigating the link between skeletal muscle and brain. Indeed, as a neurological origin of sarcopenia has been hypothesized, a new perspective on sarcopenia biomarkers may focus on the dysfunction of the neuromuscular junctions (NMJs). The core SNARE synaptosomal-associated protein of 25 kDa (SNAP25) accumulates in the plasma membrane of nerve terminals at NMJs and regulates exocytosis at peripheral and central synapses. Interestingly, mice studies have shown that SNAP25 affects the neuromuscular function. SNARE complex and, in particular, SNAP25 may represent a promising pathway to explore the molecular and cellular mechanisms regulating muscular homeostasis and concur at profiling the sarcopenia biological background.
Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.
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