Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging (“inflammaging”). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.

Senescent cells can spread the senescent phenotype to other cells by secreting senescence-associated secretory phenotype factors. The resulting paracrine senescent cells make a significant contribution to the burden of senescent cell accumulation with age. Previous efforts made to characterize paracrine senescence are unreliable due to analyses being based on mixed populations of senescent and non-senescent cells. Here, we use dipeptidyl peptidase-4 (DPP4) as a surface maker to isolate senescent cells from mixed populations. Using this technique, we enrich the percentage of paracrine senescence from 40% to 85%. We then use this enriched culture to characterize DPP4⁺ primary and paracrine senescent cells. We observe ferroptosis dysregulation and ferrous iron accumulation as a common phenomenon in both primary and paracrine senescent cells. Finally, we identify ferroptosis induction and ferrous iron-activatable prodrug as a broad-spectrum senolytic approach to ablate multiple types of primary and paracrine senescent cells.

Caspase-1 is an evolutionarily conserved inflammatory mediated enzyme that cleaves and activates inflammatory cytokines. It can be activated through the assembly of inflammasome and its major effect is to activate the pro-inflammatory cytokines; interleukin 1β (IL-1β) and interluekine-18 (IL-18). In addition to IL-1β and IL-8, several lines of evidence showed that caspase-1 targets the substrates that are involved in different metabolic pathways, including lipid metabolism. Caspase-1 regulates lipid metabolism through cytokine dependent or cytokine independent regulation of genes that involved in lipid metabolism and its regulation. To date, there are several reports on the role of caspase-1 in lipid metabolism. Therefore, this review is aimed to summarize the role of caspase-1 in lipid metabolism and its regulation.

Immunotherapy has transformed the landscape of cancer treatment, with T cell‐based strategies at the forefront of this revolution. However, the durability of these responses is frequently undermined by two intertwined phenomena: T cell exhaustion and senescence. While exhaustion is driven by chronic antigen exposure in the immunosuppressive tumor microenvironment, leading to a reversible state of diminished functionality, senescence reflects a more permanent, age‐ or stress‐induced arrest in cellular proliferation and effector capacity. Together, these processes represent formidable barriers to sustained anti‐tumor immunity. In this review, we dissect the molecular underpinnings of T cell exhaustion and senescence, revealing how these dysfunctions synergistically contribute to immune evasion and resistance across a range of solid tumors. We explore cutting‐edge therapeutic approaches aimed at rewiring the exhausted and senescent T cell phenotypes. These include advances in immune checkpoint blockade, the engineering of “armored” CAR‐T cells, senolytic therapies that selectively eliminate senescent cells, and novel interventions that reinvigorate the immune system's capacity for tumor eradication. By spotlighting emerging strategies that target both exhaustion and senescence, we provide a forward‐looking perspective on the potential to harness immune rejuvenation. This comprehensive review outlines the next frontier in cancer immunotherapy: unlocking durable responses by overcoming the immune system's intrinsic aging and exhaustion, ultimately paving the way for transformative therapeutic breakthroughs.

Globally, coffee is one of the most consumed beverages and recently, it has been a target of researchers to understand its effect on human health whether good or bad. Even though there is controversy on coffee consumption effect in cardiovascular diseases, several reports pointed out that coffee has a positive effect on the occurrence and progression of chronic non-communicable diseases including cardiovascular diseases. However, the impact of Ethiopian coffee Arabica consumption on cardiovascular diseases has not been well investigated thoroughly. The aim of the present study was to investigate the effect of habitual consumption of Ethiopian Arabica coffee on the risk of cardiovascular diseases among non-diabetic individuals in Addis Ababa. A cross-sectional study was conducted in 70 healthy individuals in Addis Ababa. The participants were 35 coffee drinkers (16 males; 19 females) and 35 non-drinkers (15 males; 20 females). Coffee consumption and demographic data were obtained by using questionnaires. Anthropometric measurements were measured according to World Health Organization standards. Blood samples were collected by trained laboratory technicians through aseptic and sterile techniques for the analysis of biochemical parameters. Serum was separated via centrifugation and transported to Addis Ababa University, College of Health Sciences, Biochemistry laboratory with an ice pack for analysis or stored at -80 °C. Results were compared between coffee consumers and non -consumers using appropriate statistical parameter. The main finding of this study was that consumption of Ethiopian origin Arabica coffee leads to a significant increase in serum free fatty acids (FFAs) and high density lipoprotein (HDL) as well as a significant decrease in triacylglycerides (TAGs) but has no significant effect in both total cholesterol (TC) and low density lipoprotein (LDL). The magnitude of the effect is similar in both sexes. The present study demonstrated that Ethiopian coffee Arabica consumption significantly affected most serum lipid levels and so it may be possible to say it has a protective effect against risks of cardiovascular diseases (CVDs). However, the correlations between coffee consumption habits and serum lipid levels require further investigation through experimental and epidemiological studies with larger sample size, including different age groups and nutritional habits.