Metabolically Active but Dysfunctional: The Impact of Senescent Cells and SASP.
Level 5 - mechanism / opinion, no new human data
Narrative review of biological mechanisms and early literature with no new human data or systematic methodology
PubMed 42635622 · doi:10.1177/15330338261481909
What was done
This narrative review summarizes molecular mechanisms linking the accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) in metabolic tissues (adipose tissue, liver, pancreas, skeletal muscle) to chronic inflammation and metabolic disease. It also evaluates emerging therapeutic approaches, including senolytics and SASP modulators (senomorphics).
What was found
The abstract reports no numerical findings or quantitative effect sizes. It qualitatively describes how metabolically active senescent cells release pro-inflammatory cytokines, chemokines, proteases, and growth factors, disrupting tissue homeostasis. This bidirectional interaction between metabolic stress and senescence contributes to insulin resistance, MASLD, and type 2 diabetes. Senolytics and SASP modulators show potential for improving metabolic parameters in preclinical and early-phase clinical evaluations.
Why it matters
Understanding the molecular interplay between cellular senescence and metabolic stress highlights senolytics and senomorphics as potential therapeutic strategies for chronic, age-associated metabolic diseases.
Limits
As a narrative review, it lacks a systematic search strategy, meta-analytic pooling, and risk of bias assessment. Quantitative data are absent in the abstract, and human evidence for senotherapeutic interventions remains limited, relying heavily on preclinical models.
Cited by
- context Senescent cells are rare in human tissues before age 50 or 60 and become detectable after the midpoint of lifespan.