Table 3.

Some Major Differences Between Senolytics and Senomorphics

Feature	Senolytics	Senomorphics	References
Definition	Compounds that selectively induce apoptosis in senescent cells, leading to their elimination.	Compounds that modulate the phenotype of senescent cells without killing them, primarily by suppressing harmful secretions.	[36,37]
Mechanism of Action	Induce apoptosis in senescent cells, leading to their elimination.	Modulate senescent cell behavior without killing them, primarily by suppressing SASP.	[49,65]
Therapeutic Goal	Remove senescent cells to reduce their harmful effects on aging and disease.	Preserve senescent cells while minimizing their pro-inflammatory and deleterious effects.	[50,119]
Target Cells	Specifically targets and eliminates senescent cells.	Alters the function of senescent cells without clearing them.	[141]
Key Molecular Targets	BCL-2 family proteins, PI3K/AKT, FOXO, p53 pathways (apoptosis regulators).	NF-κB, mTOR, SIRT1, p53/p21 pathways (inflammatory and metabolic regulators).	[31,142]]
Effect on SASP	Eliminates SASP-producing cells, thereby reducing systemic inflammation.	Suppresses SASP production while maintaining beneficial senescence functions.	[143]
Examples of Agents	Dasatinib, Quercetin, Fisetin, Navitoclax (ABT-263).	Metformin, Rapamycin, Resveratrol, Curcumin.	[130,141]
Potential Benefits	Clears damaged cells, improving tissue function and lifespan.	Reduces chronic inflammation, enhances tissue repair, and improves metabolic function.	[36,65]
Associated Risks	Risk of excessive cell depletion, potential toxicity, and off-target effects.	May require long-term use, as it does not eliminate senescent cells completely.	[4,119]
Therapeutic Applications	Used in conditions where removing senescent cells is beneficial, such as osteoarthritis, fibrosis, and neurodegeneration.	Suitable for diseases where senescent cell modification is preferred, such as metabolic disorders and neuroprotection.	[144]
Mode of Administration	Typically administered intermittently to avoid excessive depletion of senescent cells.	Requires continuous or long-term administration to sustain SASP suppression.	[40]