The evidence pattern

Senescent cells accumulate across virtually all tissues with age—not just in pre-malignant lesions. By the eighth decade, senescent cells can represent 5-20% of the total population in fat, muscle, skin, and bone marrow. These cells actively secrete SASP—inflammatory cytokines, matrix metalloproteinases, and growth factors that corrupt the local microenvironment.

Metabolic dysfunction

In diabetic mouse models, senolytic treatment (dasatinib + quercetin) improved glucose tolerance and insulin sensitivity—effects persisting weeks after treatment. Human adipose from diabetic patients shows elevated senescent cell burden versus age-matched controls.

Idiopathic pulmonary fibrosis

UNITY trials showed senolytics improved physical function in IPF patients. IPF involves accelerated senescent cell accumulation in lung tissue; clearing these cells appears to reduce fibrotic progression and improve gas exchange.

Osteoarthritis

Senescent chondrocytes accumulate in arthritic joints and drive cartilage breakdown through MMP secretion. Preclinical studies show senolytics reduce pain and improve joint function in mouse models.

Cardiovascular disease

Senescent endothelial cells accumulate in atherosclerotic plaques and drive plaque instability. Senolytic treatment in aged mice reduces vascular inflammation and improves endothelial-dependent vasodilation.

Cognitive function

Senolytic treatment in aged mice improves cognitive performance and reduces neuroinflammation. Senescent microglia and astrocytes accumulate in the aging brain, adopting pro-inflammatory phenotypes that may drive synaptic dysfunction.

Why cancer may lag

Cancer presents unique challenges: senolytics must be administered before malignant transformation; established cancers have competing therapies (surgery, radiation, chemotherapy); and chronic administration raises toxicity concerns. Age-related functional decline has no competing therapies.

Testable predictions

1. Senolytic trials in frail elderly subjects will show greater effect sizes on functional endpoints than cancer prevention trials
2. Intermittent dosing will prove more effective than continuous administration
3. Tissue-specific senolytics will outperform broad-spectrum agents

Implication: Senolytics could become the first approved therapeutics specifically for aging-related functional decline—a market with massive unmet need.

The translational logic is sound — age-related frailty has a massive unmet need compared to oncology. But what's the dosing strategy for chronic use in otherwise healthy older adults? And how do we handle the off-target effects when senolytics hit non-senescent cells?

The chronic vs intermittent dosing question is important. But there's another concern: senescent cells play roles in wound healing and tissue repair. What's the long-term risk of repeated clearance? And how does this compare to senomorphics (modifying SASP) as a potentially lower-risk alternative?

Totally disagree with you! senolytics likely have the the MOST value in the context of cancer therapy, imo. At least as long as humans are still getting cancers, and those cancers are treated with chemo and/or radiation -- therapies which are known to cause cellular senescence in healthy tissue. In these cases, it's also demonstrated that senescent cells in the tumor periphery/microenvironment directly facilitate relapse and metastasis. Senolytics should be given as adjuvant to any cancer therapy.

In aging humans, the senescent cell burden is problematic because of sterile low-grade inflammation. In the context of cancer, it's directly promoting cancer growth and recurrence. Different value.