Aging and the Importance of Understanding Senescence

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Humans have grappled for centuries with the question of whether or not we can slow the effects of aging. Understanding the biological process called 'senescence' which refers to the aging of cells, could very well hold the key to eternal youth.

As we age, so do the cells in our body. Over time as our cells age, they begin to slowly lose their ability to divide and function properly. This is not unique to humans but is the same for all forms of life as we know it. There are actually two main forms of cellular senescence, replicative senescence and stress-induced premature senescence (SIPS).

Replicative senescence can be framed as a cell’s “natural expiration date.” Each time a cell divides, its telomeres, which are the protective tips of its chromosomes, just get that little bit smaller. Eventually, telomeres become so short that the functioning cell they are attached to no longer has the ability to longer divide.

SIPS or the “stress-induced” form of Senescence, is when cells are triggered by various stressors such as oxidative stress, DNA damage, or oncogene activation, leading to cells to stop dividing as normal called “growth arrest”.

Growth arrest could also be a response to unfavourable conditions in the body. For example, when a cell's DNA is damaged, the cell might pause its division in the attempt to repair the damage.

While growth arrest perhaps sounds like a negative occurrence, it is actually an essential part of the body's regulation and a mechanism to protect itself. However, problems can arise when cells that should undergo growth arrest do not, resulting in uncontrolled cell division, which can cause cancer. Also on the other scale, if too many cells start to enter into a state of "growth arrest" and become senescent, it can contribute to aging and age-related diseases (think Alzheimer’s, heart conditions, and weakened bones).

Some examples of stress-induced Senescence include:

Oxidative Stress: Think of this as a kind of rusting from within. As our body's cells use oxygen to produce energy, but this process also produces harmful by products called free radicals. These are unstable and highly reactive molecules that can damage cells. Normally, our bodies have antioxidants to neutralize these free radicals. But if the body has far too many "free radicals" and not enough antioxidants, it can lead to a situation called oxidative stress. This then can result in damage to cells, causing aging and serious diseases such as cancer and heart disease.

DNA Damage: To put it simply, DNA is the manual in your body that instructs cells how to work properly. When these instructions get messed up due to factors like exposure to harmful radiation, some chemicals, or even errors during cell division, DNA damage can occur. If our cells are unable to repair this damage, cells could die, grow too fast or simply stop working properly (which could cause cancer).

Oncogene Activation: Oncogenes are like the acceleration pedal in a car for cell growth and division. Normally these genes help cells grow and divide in a controlled manner in the body. However, sometimes these genes can get stuck accelerating and can’t slow down, due to certain mutations or other factors. This is known as oncogene activation. This can result in cells growing and dividing too much, which can also result in tumours in the body forming, think of a stressed-out cells from them being overstimulated, like when a car speeds, and then it leads to uncontrolled growths which can also cause cancer.

It is important to note that although senescent cells have stopped dividing they are not actually entirely inactive. They continue to stay alive and release a cocktail of bioactive molecules, known as the senescence-associated secretory phenotype (SASP). SASP can cause inflammation and further damage to other cells and tissues over time. This damage is linked to many age-related diseases and ailments such as heart disease, arthritis, and Alzheimer's.

If scientists can work out how to delay, control, or even reverse senescence, it could open the door to potentially curing many age-related diseases. One example of an organisation involved in tackling senescence is the SENS Foundation, through their work on rejuvenation biotechnologies, which are therapies designed to repair or eliminate the damage caused by aging which are brought on by senescent cells.

Researchers are investigating ways to possibly develop drugs known as 'senolytics' that will selectively eliminate senescent cells. Scientists are also looking at therapies to change the behaviour of senescent cells to reduce the harmful substances they release.

Senescence does still serve some benefits, such as assisting in healing wounds, and preventing the growth of cancerous cells. Therefore, scientists must walk the difficult tightrope of minimising the negative aspects of senescence, whilst still ensuring the benefits of these cells are kept intact. Hence why targeting and reprogramming behaviours of these cells may well be the way to go.

As researchers delve deeper into the behaviours of cells, and make new discoveries, this can only open the door to revolutionary therapies that may well change how we approach natural aging all together. The future looks promising, so if these organisations can get the funding required to help accelerate their findings even further, humanity may well collectively turn back the clock and live longer together.