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Aesthetic Dermatology
The Biology of Skin Ageing
Yolanda Rosi Helfrich, Dana L Sachs and John J Voorhees
Department of Dermatology, University of Michigan, Ann Arbor
Abstract
An aged appearance of skin can result from one of two processes: intrinsic chronological skin ageing or photoageing. These processes
look similar clinically, although photoageing tends to be more dramatic, with deeper wrinkles or severe atrophy and pigmentary change.
In recent decades, substantial research has been performed to better understand the mechanisms underlying an aged appearance.
Much of this research focuses on the collagen dermal matrix, which forms the foundation of skin. In both intrinsic skin ageing and
photoageing, the collagen matrix becomes fragmented as a result of increased collagen breakdown and decreased collagen formation.
As the pathways underlying cutaneous ageing have become better understood, antiageing therapies targeting these pathways have
been developed. In addition, some existing therapies that were known to improve skin ageing have been shown to modulate these
pathways. This article explores the molecular pathways underlying skin ageing and discusses therapeutic interventions that can modify
or correct these changes.
Keywords
Photoageing, skin ageing, ultraviolet (UV) irradiation, activator protein 1 (AP-1) transcription factors, tumour growth factor-beta (TGF-β) signalling,
matrix metalloproteinase (MMP) expression
Disclosure: The authors have no conflicts of interest to declare.
Received: 5 February 2009 Accepted: 8 April 2009
Correspondence: Yolanda Rosi Helfrich, Department of Dermatology, 1910 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0314, US.
yolanda@med.umich.edu
It has long been clear that there are at least two separate pathways Molecular Pathways Underlying Photoageing
that lead to an aged appearance. Intrinsic chronological ageing of The molecular pathways underlying skin ageing were first explored in
the skin manifests as fine wrinkles, thinning, laxity and the the investigation of photoageing. Photoageing is primarily caused by
development of benign growths such as seborrheic keratoses and ultraviolet B (UVB) (290–320nm) irradiation.
8
UVA wavelengths penetrate
angiomas.
1
Photoageing, a term coined in 1986 to describe the more deeply and can also lead to photoageing.
9
UV irradiation of human
effects of chronic ultraviolet (UV) light exposure on skin,
2
presents skin in vivo results first in increased levels of reactive oxygen species
with deep wrinkles or severe atrophy, dryness, irregular (ROS) such as hydrogen peroxide (H
2
O
2
) in skin.
10
H
2
O
2
can, in the
pigmentation, sallowness, telangiectasias, pre-malignant lesions, presence of transition metals such as iron and copper, undergo
laxity and a leathery appearance.
1
Other environmental factors and conversion via the Fenton reaction to the highly reactive hydroxyl
stimuli that may result in a more aged appearance include tobacco radical.
11
The hydroxyl radical can then activate mitogen-activated
use, pollution, heat and cold.
3
protein (MAP) kinase signal transduction pathways. It does this by
rendering the epidermal growth factor (EGF) receptor constitutively
Clinical and Histological Features active.
12
Under physiological conditions, the EGF receptor exists in a low
of Photoageing and Intrinsic state of phosphorylation; protein tyrosine phosphatases maintain this
Chronological Skin Ageing physiological state by removing any phosphates that would result in
The clinical differences between intrinsic skin ageing and activation of the receptor.
13
The hydroxyl radical oxidises EGF receptor
photoageing are associated with underlying histopathological protein tyrosine phosphatase, rendering it inactive, thereby resulting in a
differences. In intrinsic skin ageing, the epidermis is atrophic, the constitutively active EGF receptor (see Figure 1).
14
The EGF receptor
dermal–epidermal junction is flattened and rete pegs are becomes activated within 15 minutes of UV exposure in human skin
diminished or absent.
4
The dermis is thinner and the number of in vivo and remains activated for at least two hours.
15
fibroblasts and levels of collagen are decreased.
5
In photoageing,
the epidermis can be either thickened or atrophic. A characteristic There are three classic MAP kinase pathways in mammalian cells:
histopathological feature of photoageing is solar elastosis, the extracellular signal-regulated kinase (ERK), cJun amino-terminal kinase
accumulation of clumped elastin-containing material just below the (JNK) and p38. In human skin in vivo, UV irradiation activates all three
dermal–epidermal junction.
6
Collagen, which makes up roughly 90% pathways.
15
The primary end effector of all three MAP kinase pathways
of protein in the dermis, is disorganised.
7
is transcription factor activator protein-1 (AP-1). AP-1 is most typically
© TOUCH BRIEFINGS 2009 39
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