Citation: Shuhan Zhang, Xinyue Guo, Longhui Hao, Yu Jiang, Zhiyang Chen, Jia Wang, Liuyi Ran, Yanfang Yang, Hongliang Wang, Yannian Wang, Jun Ye, Yuling Liu. The battle against skin aging: Advances in natural anti-aging compounds and innovative delivery systems[J]. Chinese Chemical Letters, ;2026, 37(7): 112503. doi: 10.1016/j.cclet.2026.112503 shu

The battle against skin aging: Advances in natural anti-aging compounds and innovative delivery systems

Shuhan Zhang ^{a, b, c} ,
Xinyue Guo ^{a, b, c} ,
Longhui Hao ^{a, b, c} ,
Yu Jiang ^{b, c} ,
Zhiyang Chen ^{b, c} ,
Jia Wang ^d ,
Liuyi Ran ^d ,
Yanfang Yang ^{b, c} ,
Hongliang Wang ^{b, c, d, *,} ,
Yannian Wang ^{a, *,} ,
Jun Ye ^{b, c, *,} ,
Yuling Liu ^{b, c, *,}

a.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
c.
Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
d.
University-Town Hospital of Chongqing Medical University, Chongqing 401331, China

wanghl@imm.ac.cn

103040107@syphu.edu.cn

yelinghao@imm.ac.cn

ylliu@imm.ac.cn

Received Date: 15 November 2025
Revised Date: 3 February 2026
Accepted Date: 5 February 2026
Available Online: 6 February 2026

Figures(5)

Skin aging is a multifactorial biological process driven by oxidative stress (OS), chronic inflammation, cellular senescence, mitochondrial dysfunction, and non-enzymatic glycation (NEG), and is markedly accelerated by environmental stressors such as ultraviolet radiation (UVR) and air pollution. Natural bioactive compounds, including flavonoids, polyphenols, terpenoids, alkaloids, vitamins, polysaccharides, peptides, and indole derivatives, have demonstrated considerable potential in mitigating these processes through multi-target antioxidant, anti-inflammatory, anti-photoaging, and extracellular matrix (ECM)–protective mechanisms. However, their clinical and cosmetic translation is often limited by poor solubility, chemical instability, and insufficient skin penetration. Rather than providing a simple compilation of existing studies, this review offers a mechanism-oriented and delivery-driven synthesis of recent advances in natural anti-skin-aging research. We systematically integrate current knowledge on the molecular drivers of skin aging with a critical comparison of emerging transdermal and nanotechnology-based delivery systems, including lipid-based, polymer-based, inorganic/hybrid, and nucleic acid–assembled nanocarriers. Particular attention is given to how rational carrier design modulates stability, permeability, skin-layer targeting, and controlled release behavior. Furthermore, this review critically discusses current limitations, contradictory findings across studies, and key translational challenges, and identifies promising future research directions, such as stimuli-responsive systems, skin-layer-specific targeting, and mechanism-guided material selection. By bridging biological mechanisms with delivery material innovation, this work provides a forward-looking framework for the development of safer, more effective, and scientifically grounded anti-skin-aging therapeutics and cosmeceuticals.
- Skin aging,
- Natural compounds,
- Anti-aging,
- Transdermal drug delivery system,
- Nanocarriers
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