Lab Expectations

The regulation of ER stress and autophagy during viral infection is an important factor in the balance of virus and host survival. In this series, we look at pathways that are regulated through cellular responses to virus, as well as in response to virally encoded proteins. Infection of the coronaviruses SARS-CoV and SARS-CoV-2 causes severe lung injury with extensive damages to alveolar and bronchial epithelial cells, and produces extra-pulmonary damage.

The regulation of cell death during viral infection is an important factor in the balance of virus and host survival. In this series, we look at pathways that are regulated through cellular responses to virus, as well as in response to virally encoded proteins. Infection of the coronaviruses SARS-CoV and SARS-CoV-2 causes severe lung injury with extensive damages to alveolar and bronchial epithelial cells, and produces extra-pulmonary damage.

In response to a variety of environmental factors – like ionizing radiation, exposure to chemotherapeutic drugs, oxidative stress, DNA damage, mitochondrial dysfunction, or oncogene activation – cells may permanently cease proliferation and enter a state known as cellular senescence. Senescence occurs during normal developmental processes, in wound healing, and as a consequence of aging and age-related disease. Accordingly, understanding why senescence contributes to these processes may lead to the development of pro- and anti-senescence therapies to treat a range of diseases.

Cellular senescence occurs when cells cease proliferation and irreversibly exit the cell cycle. While this occurs as a normal process during development and tissue remodeling, senescence has also been linked to a general decline in tissue function during aging as well as a number of disease states. These include the progression of cancer, atherosclerosis, diabetes, and neurodegeneration. Accordingly, understanding why senescent cells impact these conditions and developing ways to target their removal may provide therapeutic value for the treatment of many human conditions.

Senescence is a cellular state during which cells remain metabolically active, but irreversibly withdraw from the cell cycle and fail to respond to proliferation-inducing stimuli. Senescent cells influence a number of physiological and pathological processes from cancer to diabetes and aging. Accordingly, understanding why senescence contributes to these conditions may lead to the development of pro- and anti-senescence therapies to treat a range of diseases.

Senescence, the cessation of cell division and permanent withdrawal from the cell cycle, is a process that occurs throughout the lifespan — during embryogenesis, growth and development, tissue remodeling, and in wound healing. Senescent cells increase in number during aging and have been implicated in the decline of organismal function over time, as well as in the progression of age related diseases. These include metabolic and cardiovascular disorders, neurodegenerative disease, and cancer. In mammals, aging causes the gradual dysfunction of multiple tissue systems in a heterogeneous fashion, ultimately leading to death. Understanding how and why senescence contributes to the aging process may lead to therapies to slow or even reverse its progression.

Senescence is the irreversible arrest of proliferation in response to a variety of cellular stressors. This state is associated with changes in intracellular signaling pathways, as well that the secretion of proteins that affect the surrounding tissue microenvironment. Most notably, senescent cells exhibit a persistent DNA damage response, the activation of proteins which control cell cycle arrest, and the senescence associated secretory phenotype. Senescent cells are also resistant to apoptosis and demonstrate altered metabolic activity. Determining why changes in cellular signaling lead to senescence is key to understanding how senescence contributes to normal and pathological processes affecting human health.

The ability of cells to recognize external signal cues (ligands and nutrients) and appropriately respond to a rapidly changing environment involves crosstalk among major cellular signaling networks (1-2). These complex pathways sense intracellular nutrients, metabolic flux, and stress and integrate these distinct signals through numerous downstream effectors (1-2). As a scientist, I find trying to understand the intricate nature of pathways (where they overlap and intersect) to be an interesting puzzle to tease apart.

Cellular senescence is a state of stable cell cycle arrest under which cells remain metabolically active, but no longer divide and do not respond to growth-promoting stimuli. Senescence is triggered by a variety of cellular stressors. These include environmental factors like ionizing radiation or exposure to chemotherapeutic drugs, oxidative stress, DNA damage, mitochondrial dysfunction, and oncogene activation. This process provides a defense mechanism to maintain tissue homeostasis through the sequestration of damaged cells. Senescent cells influence a number of physiological and pathological processes from cancer to diabetes and aging. Accordingly, understanding why senescence contributes to these conditions may lead to the development of pro- and anti-senescence therapies to treat a range of diseases.

Changes in cellular health in response to exogenous stimuli can provide keen insight into the biological mechanisms that govern the relationship between cells and their environment and can dramatically influence the interpretation of experimental results. These reasons underscore why it is important to understand cytotoxicity and to employ assays to measure its impact.