How Senesence Drives Aging

One of the main hallmarks of aging is the accumulation of senescent cells. As we age, senescent cells grow at a compounding rate, accelerating the aging process. Senescent cells are often called “zombie cells,” as they remain dysfunctional but cannot replicate or undergo programmed cell death.

Cell senescence induces a dysfunction characterized by excess growth, excessive production of disruptive cell output, and excess consumption. This cellular excess ultimately leads to the deterioration of tissue function, which accelerates the process of aging.

Manifestations of human senescence are very consistent across all organisms: skin wrinkles and male baldness, insulin-resistance and osteoporosis, hypertension and atherosclerosis, obesity and diabetes, cancer and Alzheimer’s disease.

1. Senescent Drives Inflammation to Excessive Levels.

Across all cell types, one of the defining characteristics of a senescent cell is its excessive release of inflammatory molecules. Senescent cells release a “witch’s brew” of pro-inflammatory cytokines, chemokines, growth and mitogenic factors, pro-senescent proteins, and proteases that make up the Senescent Associated Secretory Phenotype (Senescent SASP).

2. Senescent Cells Transform Health Cells Into Senescence.

The inflammatory response to the SASP causes the adjacent healthy cells to transform into senescent. The SASP and inflammatory response activate the senescent programming of neighboring cells.

This is why we call senescent cells’ zombie cells’—they don’t merely release harmful chemicals; inflammatory signaling can cause adjacent healthy cells to become senescent, as the SASP and the resulting inflammation can activate senescent programming in these neighboring cells.

A vicious cycle develops—senescence begets more senescence. This process contributes to the spread of cellular dysfunction and ultimately underscores the complexity of senescence and its role in aging and disease.

3. Senescent Cell Growth Compounds as We Age

When we are young, we have regularly scheduled clearances of senescent cells—as new senescent cells are introduced, they get cleared out at an equal rate. This is what keeps our tissues functional and healthy. The proportion of functional cells to dysfunctional cells remains balanced in favor of the functional cells due to this clearance mechanism.

However, as we age, the rate at which we accumulate senescent cells outpaces the rate at which we eliminate them. The accumulation of these hyper-functional cells ultimately drives aging later in life. As we accumulate more and more senescent cells, the proportion of dysfunctional cells to functional cells begins to shift, contributing to the gradual decline in tissue function that characterizes the aging process.

Here are some additional resources on senescence as an accelerant of aging: