Lab Expectations

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.

Apoptosis is a highly regulated form of programmed cell death that occurs in multicellular organisms during development, throughout the lifespan, and in response to cellular stress. Nuclear condensation, cell shrinkage, membrane blebbing, and DNA fragmentation are characteristic features of the cellular disassembly that occurs during this form of cell death. A family of proteolytic enzymes, called caspases, serves as the central regulators of apoptosis, and their activity, in turn, is balanced by myriad additional pro-apoptotic and anti-apoptotic proteins. The dysregulation of apoptosis occurs in and contributes to the pathology of several disease states, including autoimmune disorders, neurodegenerative diseases, and cancer. Therefore, understanding how and why apoptosis influences these biological processes may lead to advances in therapies to treat and benefit human health.

The production of new cells through cellular proliferation impacts the development, growth, and maintenance of all tissues in the body. This process must be tightly regulated, since uncontrolled cell division – as seen in various cancers – can lead to tumor formation and disrupt organ function. These broad implications for biological activities highlight the importance of understanding and accurately measuring cellular proliferation in a variety of contexts.

The health of cells in culture is critical to the success of your experiments. Have you ever been excited about the experimental results of a knock-down, drug treatment, or culture condition, only to realize later that the effects are skewed due to the amount of cell death that occurred in your samples? Measuring and comparing cell viability in your assays is important, whether it’s the data you’re pursuing or an important control in your experiment.

Fibrosis is a disease that is characterized by scarring and hardening of tissues and organs. Fibrosis can affect all tissues of the body, and left unchecked, can result in organ failure and death. What causes it? Believe it or not, it is a process that stems from wound healing that has gone awry.