The one way that Stem cells maintain health: they take long naps

Quiescent stem cells means that cells are resting in the G0 phase of the cell cycle and are non-proliferative.

Stem cells that are in the quiescent phase are very different than those that are actively proliferating. Quiescent stem cells are smaller than proliferating stem cells (as seen in image below). They also: 

• do not use as much energy
• tend to break down glucose in the cytoplasm to produce energy (glycolysis) versus using the mitochondria (oxidative phosphorylation)
• produce less Reactive Oxygen Species (ROS), given that they are using less oxygen to break down glucose
• have lower amounts of RNA in the cell, as they are producing less protein in their dormant state 
• have less growth receptors in their membranes (for example, lower levels of insulin-binding proteins)

Quiescence is good for the cell. Taking long naps allows the cell to develop increased resistance to stressors as well as cleaning out the cupboards from unused and dysfunctional proteins (autophagy) (2, 5). 

The converse is also true. If one takes proliferating stem cells and creates conditions of starvation, low oxygen levels, lower levels of growth factors, overcrowding of cells, the proliferating stem cells will enter a period of quiescence (4). 

By employing the strategies listed above, quiescent stem cells remain in a dormant, non-dividing state for prolonged periods while retaining their ability to activate and regenerate tissues when necessary.

This is one reason why calorie restriction is thought to lead to longevity and help minimize aging-related disease (6,7,8,9).

Creating the ability for cells to enter quiescence helps in their long term survival. In fact, some stem cells are particularly resilient when they enter a period of quiescence.

The good: stem cells can be harvested from cadavers

Stem cells are versatile cells that provide a pool for regenerating tissues. Amazingly, even though almost all tissue cells die after the organism dies, many stem cells remain alive for several days - and weeks, in the case of muscle stem cells (10).

The reason for this is the stem cells enter a dormant state as their environment becomes nutrient-depleted, hypoxic, and replete with the toxic molecules and ions of a necrotic environment. Studies have demonstrated that it is possible to harvest those stem cells and allow them to proliferate in a supportive environment (10, 11).

In fact, the abnormal environment seems to select for more robust and highly undifferentiated stem cells. This means that those undifferentiated stem cells are not restricted to one tissue, and potentially could regenerate into different cell types (10).

The bad: cancer stem cells can develop quiescence in response to cancer treatment, which may lead to recurrence

The factors that make stem cells live another day and proliferate unfortunately also predisposes to the unsuccessful eradication of cancer cells. As tumors grow, the cancer cells compete for nutrients, blood supply, and oxygen. The tumor cell niche is perfect for cancer stem cells to survive, as it is a hypoxic, acidic, and nutrient-poor niche. 

In addition, therapies like radiation and chemotherapy invite cancer stem cells that have not been destroyed to enter a stage of dormancy. This is one way that cancer is thought to recur after years of remission (1, 12). 

Adult stem cells are critical to maintain our overall health. Clearly whatever we can do to keep our stem cells vibrant equates directly with our well-being, and very likely our longevity. 

The challenge is to keep the stem cells unstimulated and quiescent. It is only when stem cells rest for long periods of time in a deficient state (low nutrients, oxygen, growth factors) that they can undergo regular spring cleaning cycles. 

In fact, placing stem cells in deficient states promotes deeper quiescence: these dormant states mean that the cells are in a type of "suspended animation": they have not died. They are patiently waiting for signals to regenerate and repair tissues.