Immunity & Ageing

Cellular senescence is an essentially irreversible arrest of cell proliferation coupled to a complex senescence-associated secretory phenotype (SASP). The senescence arrest prevents the development of cancer, and the SASP can promote tissue repair. Recent data suggest that the prolonged presence of senescent cells, and especially the SASP, could be deleterious, and their beneficial effects early in life can become maladaptive such that they drive aging phenotypes and pathologies late in life. It is therefore important to develop strategies to eliminate senescent cells. There are currently under development or approved several immune cell-based therapies for cancer, which could be redesigned to target senescent cells. This review focuses on this possible use of immune cells and discusses how current cell-based therapies could be used for senescent cell removal.

Alzheimer Disease (AD) is the most common neurodegenerative disorder worldwide, and account for 60% to 70% of all cases of progressive cognitive impairment in elderly patients. At the microscopic level distinctive features of AD are neurons and synapses degeneration, together with extensive amounts of senile plaques and neurofibrillars tangles. The degenerative process probably starts 20–30 years before the clinical onset of the disease. Senile plaques are composed of a central core of amyloid β peptide, Aβ, derived from the metabolism of the larger amyloid precursor protein, APP, which is expressed not only in the brain, but even in non neuronal tissues. More than 30 years ago, some studies reported that human platelets express APP and all the enzymatic activities necessary to process this protein through the same pathways described in the brain. Since then a large number of evidence has been accumulated to suggest that platelets may be a good peripheral model to study the metabolism of APP, and the pathophysiology of the onset of AD. In this review, we will summarize the current knowledge on the involvement of platelets in Alzheimer Disease. Although platelets are generally accepted as a suitable model for AD, the current scientific interest on this model is very high, because many concepts still remain debated and controversial. At the same time, however, these still unsolved divergences mirror a difficulty to establish constant parameters to better defined the role of platelets in AD.

Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.

With the ageing of the world population, osteoporosis has become a problem affecting quality of life. According to the traditional view, the causes of osteoporosis mainly include endocrine disorders, metabolic disorders and mechanical factors. However, in recent years, the immune system and immune factors have been shown to play important roles in the occurrence and development of osteoporosis. Among these components, regulatory T (Treg) cells and T helper 17 (Th17) cells are crucial for maintaining bone homeostasis, especially osteoclast differentiation. Treg cells and Th17 cells originate from the same precursor cells, and their differentiation requires involvement of the TGF-β regulated signalling pathway. Treg cells and Th17 cells have opposite functions. Treg cells inhibit the differentiation of osteoclasts in vivo and in vitro, while Th17 cells promote the differentiation of osteoclasts. Therefore, understanding the balance between Treg cells and Th17 cells is anticipated to provide a new idea for the development of novel treatments for osteoporosis.

The SARS-CoV-2 pandemic represents one of the greatest infectious challenges to humanity in recent history. One of the striking features of infection is the heterogeneous clinical response with worse outcomes observed in older patients and those with underlying health conditions. To date the potential impact of previous infection history has been poorly investigated as a potential determinant of risk. Cytomegalovirus (CMV), a persistent herpesvirus infection whose prevalence increases with age, is a major modulator of immune function and several observations suggest that infection might act to influence clinical outcome following SARS-CoV-2 infection. In particular, CMV is associated with the acceleration of immune senescence and has been linked to a range of cardiovascular and metabolic disorders. This review addresses mechanisms by which cytomegalovirus infection may act to worsen the clinical outcome of SARS-CoV-2 infection, discusses how these potential links could be investigated, and assesses the potential significance of any findings that emerge.