Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation

Area of Science:

• Gerontology
• Immunology
• Cell Biology

Background:

• Aging leads to reduced resilience and increased disease risk.
• Cellular senescence, marked by the senescence-associated secretory phenotype (SASP), is a key aging hallmark driving inflammation.
• Senescent cells accumulate with age, releasing inflammatory factors that alter tissue environments.

Purpose of the Study:

• To review the current understanding of tissue-specific SASP programs.
• To highlight mechanisms amplifying local senescence into systemic inflammation.
• To discuss the role of nucleic acid-sensing pathways and immune evasion in senescent cell persistence.

Main Methods:

• Literature review synthesizing current research on cellular senescence and aging.
• Analysis of tissue-specific SASP variations across immune, vascular, metabolic, hepatic, and neural systems.
• Examination of molecular mechanisms driving SASP and its systemic effects.

Main Results:

• SASP composition is heterogeneous, varying by cell type, metabolism, and stressor.
• Nucleic acid-sensing pathways (e.g., cGAS-STING, RIG-I) sustain senescence-associated inflammation.
• Senescent cells employ immune-evasion tactics, contributing to their persistence in aging tissues.

Conclusions:

• Senescent cell accumulation is a critical link between molecular damage and inflammaging.
• Mechanisms like endocrine signaling, extracellular vesicles, and sex-dependent modulation amplify senescence-driven inflammation.
• Targeting cellular senescence and SASP may offer therapeutic strategies for age-related diseases.