Current Drug Targets - Volume 17, Issue 4, 2016

Cellular senescence is the state of permanent proliferation cessation. There are two types of cell senescence. One is replicative senescence, which relies on telomere length-dependent limit of cell divisions. The second is stress-induced premature senescence (SIPS) which is telomere- independent. Cell senescence is a barrier to cancer. Paradoxically senescent cells, which are metabolically active secrete factors which Read More

Aging is accompanied by a progressive decline of endothelial function and a progressive drift toward a systemic pro-inflammatory status that has been designated “inflammaging”. Both phenomena are accelerated and exacerbated in patients with the most common age-related diseases (ARDs), including cancer. The finding that chronic cell stress activates a pro-inflammatory program leading to acquisition of the senesce Read More

When DNA damage occurs, cells stop the cell cycle and DNA repair can take place. However, if DNA damage exceeds DNA repair capacities, cells undergo either apoptosis or senescence. These mechanisms preclude the proliferation of cells with heavily damaged DNA, thus protecting the organism against tumour development. When individuals are exposed to stress, the hypothalamic-pituitary-adrenal (HPA) axis and the s Read More

Cancer and aging are two similar processes representing the final outcome of timedependent accumulation of various irreversible dysfunctions, mainly caused by stress-induced DNA and cellular damages. Apoptosis and senescence are two types of cellular response to damages that are altered in both cancer and aging, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the Read More

Endogenous retroelements (ERs) represent nearly half of the human genome. Considered up to recent years as “functionless” DNA sequences, they are now known to be involved in important cellular functions such as stress response and generation of non coding regulatory RNAs. Moreover, an increasing amount of data supports the idea of ERs as key players in cellular senescence and in different senescence-relat Read More

Before the last decade, attempts to identify the genetic factors involved in the susceptibility to age-related complex diseases such as cardiovascular disease, diabetes and cancer had very limited success. Recently, two important advancements have provided new opportunities to improve our knowledge in this field. Firstly, it has emerged the concept of studying the molecular mechanisms underlying the age relate Read More

In the 70-80th of last century, it has been shown that the antidiabetic biguanide drugs phenformin (PF) and buformin (BF) can exert an inhibitory action on carcinogenesis in animal models and increase from 5 to 10-years survival of cancer patients. Since 2005, after first evidence publication of the capacity of metformin (MF), another biguanide, to prevent development of malignant tumors in individuals with type 2 diabetes (T Read More

The possibility to target cellular senescence with natural bioactive substances open interesting therapeutic perspective in cancer and aging. Engaging senescence response is suggested as a key component for therapeutic intervention in the eradication of cancer. At the same time, delaying senescence or even promote death of accumulating apoptosis-resistant senescent cells is proposed as a strategy to prevent ag Read More

Senescence was originally identified by the finite lifespan of normal cells that is a consequence of telomere shortening with each cycle of DNA replication. Cells undergoing replicative senescence display pronounced morphological and biochemical changes such as flattening and/or enlargement, increases in p21WAF1 and/or p16INK4A, a senescence-associated secretory phenotype, and often senescence-associated Read More

Cardiovascular and cerebrovascular diseases (CCVD) are a major and increasing health burden worldwide. Although treatments have been made a certain progress, the development of novel therapies for patients remains a major research object. There are a lot of drugs against CCVD, but most of them lack tissue specificity with a short half-life, which seriously limits their extensive clinical application. Utilization of some pathophy Read More

Articular cartilage is a physiologically non-self-renewing avascular tissue with a unique cell type, the chondrocyte, which functions as producing and maintaining the extracellular matrix of cartilage. Cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules. The network sheds light on these mechanisms that appear to be highly relevant to both the identification of path Read More