# Dermal Fibroblast Senescence: The Central Hub of Skin Aging—From Intrinsic Dysfunction to Microenvironmental Remodeling

## TL;DR

This paper explores how aging skin is driven by dermal fibroblast dysfunction and how this leads to wrinkles and loss of elasticity.

## Contribution

The paper reviews the mechanisms of fibroblast senescence and its impact on the skin microenvironment, highlighting gaps in current anti-aging treatments.

## Key findings

- Dermal fibroblasts undergo intrinsic aging through telomere shortening and pathway dysregulation.
- Senescent fibroblasts release SASP factors that disrupt skin cell functions and worsen aging.
- Current anti-aging strategies face challenges with delivery and targeting efficiency.

## Abstract

Skin aging commonly manifests as deepening wrinkles, loss of elasticity, and weakened barrier function, resulting from the long-term accumulation of multiple biological processes. Dermal fibroblasts, as the primary source of extracellular matrix, not only provide structural support but also play an active role in aging. On one hand, they undergo intrinsic aging due to telomere shortening, mitochondrial decline, and dysregulation of signaling pathways (e.g., TGF-β, mTOR). On the other hand, they release inflammatory cytokines and proteases via the senescence-associated secretory pattern (SASP), disrupting keratinocyte function, melanin distribution, immune surveillance, and even microvascular and adipose tissue functions. This destabilizes the matrix equilibrium and exacerbates inflammation, creating a vicious cycle. While strategies like dasatinib/quercetin, rapamycin, or retinol show promise, they remain constrained by transdermal efficiency and targeting limitations. This review aims to elucidate these mechanisms and interactions, providing insights for developing more effective anti-aging interventions.