Lab Expectations

Cellular senescence is defined by permanent cell cycle arrest. Senescent cells accumulate with age and contribute to the normal aging process as well as age-related disorders. The link between senescence, aging, and age-related pathologies, including cancer, neurodegeneration, and metabolic and cardiovascular diseases have largely fueled the senescence research field.

Cancer cells resist inhibitory signals that might otherwise stop their growth. The major pathways involved are Autophagy and Death Receptor Signaling (Apoptosis), both of which can ultimately lead to cell death, and reduction in tumor growth.

Cancer cells can revert to a pre-differentiated, stem-cell-like phenotype, allowing uninhibited cellular division and other metabolic adaptations that enable survival in adverse conditions.

Cancer cells stimulate their own growth, which means they become self-sufficient in growth signals, and no longer depend on external signals (like Epidermal Growth Factor EGF/ EGFR). Proliferation depends highly on these three important pathways: Akt, MAPK/Erk, and MTOR.

Molecular oxygen (O₂) is an essential element for metazoan life. Among its many roles, O₂ functions as the final electron acceptor (oxidizing agent) during oxidative phosphorylation, a metabolic chain-reaction that generates energy in the form of ATP.

Cancer cells stimulate the growth of blood vessels to supply nutrients to tumors. Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. This plays an important role in tumor growth.

Over the last 50 years laboratories have been able to demonstrate through experimentation the processes contributing to cell death. Early discoveries focused on morphological features of cell death and classifications into apoptosis and necrosis. Since then, there have been many more discoveries regarding the programmed cellular pathways contributing to apoptosis.

Cancer cells need a lot of energy to grow fast—to do so, they show abnormal metabolic pathways.

Type 2 diabetes is a growing epidemic, and is recognized as one of the most serious metabolic disease worldwide. A multifactorial disease, type 2 diabetes is a perfect example of metabolic miscommunication between different organs resulting in a pathological outcome. According to CDC in the United States, 29.1 million people in the United States have diabetes, and 8.1 million may be undiagnosed. The disease affects more than 1 in every 10 adults, and seniors aged 65 and above are most affected. What makes the disease morbid are the secondary complications associated with it; atherosclerosis and cardiomyopathy are the leading cause of death in people diagnosed with type 2 diabetes. The need for an effective treatment has become a global health priority.

Reuben Shaw, Ph.D

Professor, Molecular and Cell Biology Laboratory, Deputy Director, Salk Cancer Center, The Salk Institute for Biological Studies

AMPK, a highly conserved sensor of cellular energy status, is found in all eukaryotic cells and maintains metabolic homeostasis by reprogramming growth, metabolism, and autophagy in the face of cellular stresses.