SASP stands for senescence associated secretory phenotype, a complex mixture of pro-inflammatory molecules, enzymes and growth factors released by senescent cells. These secretions play a major role in how senescent cells influence their environment and they are considered one of the most harmful aspects of cellular senescence in the context of aging and chronic disease.
While it has some beneficial roles in wound healing and tumor suppression, its chronic activation contributes to tissue degeneration, inflammation and age related decline, making it a key target in longevity science.
What SASP is
When a cell becomes senescent, meaning it permanently stops dividing in response to stress or damage, it doesn’t simply go silent. Instead, it often begins releasing a mix of signaling molecules known as the senescence-associated secretory phenotype. These secretions include:
- Cytokines (e.g. IL-6, IL-1β, TNF-α);
- Chemokines (e.g. MCP-1);
- Growth factors (e.g. VEGF, GM-CSF);
- Proteases (e.g. matrix metalloproteinases or MMPs).
Together, these substances affect the local tissue environment by promoting inflammation, remodeling of the extracellular matrix and attracting immune cells.
SASP can be beneficial in the short term, helping to recruit immune responses and support tissue repair. But when senescent cells accumulate and persist, it becomes chronically harmful.
SASP and aging
The persistent presence of SASP producing cells is a major contributor to inflammaging, the chronic, low grade inflammation that increases with age. It affects surrounding cells by:
- Inducing secondary senescence (turning nearby cells senescent);
- Disrupting tissue structure and function;
- Inhibiting stem cell activity and tissue regeneration;
- Weakening immune surveillance and promoting immune exhaustion.
This creates a pro-aging feedback loop, where one senescent cell can trigger widespread dysfunction in the surrounding tissue. Over time, this accelerates the onset of conditions such as:
- Osteoarthritis and osteoporosis;
- Neurodegenerative diseases;
- Cardiovascular disease;
- Cancer development and metastasis.
In this way, it is more than a symptom of aging, it’s a driver of biological decline.
Regulating or reducing SASP
There are several ways to reduce the impact of SASP on aging tissues:
Lifestyle strategies
- Exercise reduces the burden of senescent cells and lowers inflammatory markers;
- Caloric restriction and fasting may limit SASP expression by reducing oxidative stress and metabolic damage;
- Quality sleep and stress management help maintain immune function and cellular repair.
Nutritional compounds
Some natural compounds have been shown to suppress its factors or target senescent cells:
- Quercetin: a flavonoid that modulates inflammation and is used in senolytic combinations;
- Fisetin: another senolytic compound with anti-SASP activity;
- Curcumin: inhibits NF-κB signaling, a key driver of SASP production;
- Resveratrol and metformin: support metabolic balance and may reduce senescent signaling.
Experimental therapies
- Senolytics (e.g. dasatinib + quercetin): selectively remove SASP producing cells:
- Senomorphics: such as rapamycin and NAD+ precursors, suppress SASP activity without killing the cell;
- Gene therapies and immunotherapies targeting senescent cells are also under development.
These interventions aim to create a healthier cellular environment by controlling or eliminating the harmful effects of the SASP.
SASP vs. senescence
While cellular senescence is the process where cells stop dividing, SASP is what those cells secrete. Not all senescent cells produce a harmful SASP,and some may even have protective effects under the right circumstances.
However, when senescent cells resist removal and continue to secrete it, they become pro-inflammatory and pro-aging agents. Targeting it, either by suppressing it or clearing the cells producing it, is one of the most promising frontiers in anti-aging science.
