skin ageing

Overview

Ageing is a universal concern as people worldwide are living longer. According to world demographics, the proportion of the population aged between 65 and 85 is steadily growing in all countries. As a result of improved global health conditions, the increasing ageing population leads to new challenges in managing age-related skin disorders.

At a biological level, skin ageing results from intrinsic factors like genetic predisposition, oxidative stress, etc., leading to fine wrinkles and loss of skin elasticity. Sun exposure or pollutants are extrinsic factors that accelerate skin ageing, resulting in premature loss of skin homeostasis and barrier function, as well as hyperpigmentation.

To design interventional strategies/compounds that will address various skin conditions, a deep understanding of the molecular pathways underpinning the ageing process is critical.

Our approach

The Ageing Programme brings together biologists, engineers, and clinicians to understand the mechanisms driving skin ageing, enabling us to develop better treatments to slow the ageing process, treat age-related skin disorders and improve patient care.

Asian skin ages differently from Caucasian skin and can be more prone to skin conditions (e.g. hyperpigmentation). One focus area is the study of the differences between Asian and Caucasian skin in detail so that more customised treatments can be developed.

Another goal of the Ageing Programme is to understand how genetics, lifestyle and environmental factors impact our skin, with the goal of developing more effective treatments to delay stress-induced skin ageing.

Enhancing skin health

We are working to identify and understand the molecular drivers that promote a healthy skin barrier. Our research has shown that maintaining appropriate polyamine levels is essential for forming a healthy skin barrier and is important for efficient wound healing. We explore how polyamines can promote skin barrier formation and hope to develop polyamine-derived technologies to enhance skin health. Additionally, we are also working on manipulating polyamine levels to improve patient care in the context of certain age-associated skin disorders.  Additional projects in the program focus on understanding the role of epigenetic changes in the promotion of a healthy skin barrier and understanding how these marks change and drive skin ageing.

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SELECTED THEME PUBLICATIONS

1. Rahim AB, Lim HK, Tan CYR, Jia L, Leo VI, Uemura T, Hardman-Smart J, Common JEA, Lim TC, Bellanger S, Paus R, Igarashi K, Yang H, Vardy LA. (2021) The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation. J Invest Dermatol. 2021 Sep;141(9):2178-2188.e6. doi: 10.1016/j.jid.2021.01.039. Epub 2021 May 11.

2. Sridharan A, Shi M, Leo VI, Subramaniam N, Lim TC, Uemura T, Igarashi K, Thng S, Tan, SN, Vardy LA. (2020) The polyamine putrescine promotes human epidermal melanogenesis. J Invest Dermatol. Epub Feb 28 PMID:32119868 10.1016/j.jid.2020.02.009

3. Kheng LH, Rahim AB, Leo VI, Shatarupa D, Lim TC, Uemura T, Igarashi K, Common J, Vardy LA. (2018) Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing. J Invest Dermatol. 2018 Dec;138(12):2653-2665. doi: 10.1016/j.jid.2018.05.029. Epub 2018 Jun 12.

4. Dube CT, Jahan FRS, Lim CY (2021) Key changes in chromatin mark mammalian epidermal differentiation and ageing. Epigenetics. 2021 Apr 23:1-16. doi: 10.1080/15592294.2021.1917812.

IDENTIFYING AGED CELLS

Ageing manifests itself in many ways such as wrinkling and pigmentation. Our goal is to identify aged or senescent cells within the skin and explore how the different senescent cell types contribute to skin ageing. Our goal is to remove or modulate the function of these cells to ameliorate age-associated phenotypes. Lastly, we are studying the fundamental processes that drive ageing by studying human diseases characterized by premature ageing.

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Selected theme publications

1. Chojnowski A#, Ong PF#, Foo MXR, Liebl D, Hor LP, Stewart CL, Dreesen O* (2020). Heterochromatin loss as a determinant of progerin-induced DNA damage in Hutchinson-Gilford Progeria. Aging Cell, Mar;19(3):e13108. 10.1111/acel.13108

2. Wang AS and Dreesen O* (2018). Biomarkers of Cellular Senescence and Skin Aging. Frontiers in Genetics, Aug 23;9:247. 10.3389/fgene.2018.00247

3. Chojnowski A, Ong PF, Wong ESM, Lim JSY, Mutalif RA, Navasankari R, Dutta B, Yang H, Liow YY, Sze SK, Boudier T, Wright GD, Colman A, Burke B, Stewart CL*, Dreesen O* (2015). Progerin reduces LAP2α:telomere association in Hutchinson-Gilford progeria syndrome. eLife, Aug 27;4;e07759. 10.7554/eLife.07759

4. Dreesen O*, Chojnowski A, Ong PF, Zhao TY, Common JE, Lunny D, Lane EB, Lee SJ, Vardy LA, Stewart CL, Colman A* (2013). Consequences of Lamin B1 fluctuations on cellular proliferation and senescence. Journal of Cell Biology, Mar 4;200(5):605-17. 10.1083/jcb.201206121

Anti-ageing molecules

Our research topics include both basic and translational projects, emphasizing stemness, premature ageing, and photoageing. 

We use 2D culture of human primary keratinocytes (HPKs) and 3D organotypic skin models to study the molecular pathways that regulate the HPK shift from proliferation to differentiation/senescence in the human skin epidermis. In addition, we are also investigating mechanisms of action of anti-ageing molecules ranging from cell cycle and metabolism regulators to nutraceuticals.

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Selected Theme Publications

1. Tan, C.Y.R., Tan, C.L, Chin, T., Morenc, M., Ho C.Y., Rovito, H.A., Quek, L.S., Soon A.L., Lim, J.S.Y., Dreesen O., Oblong, J.E. and Bellanger, S*. 2021. Nicotinamide prevents UVB- and oxidative stress-induced photoaging in human primary keratinocytes. Journal of Investigative Dermatology, in press. DOI: 10.1016/j.jid.2021.10.021

2. Tan, C.L., Chin, W.K., Tan, C., Rovito, H., Quek, L.S., Oblong, J.E. and Bellanger S*. 2019. Nicotinamide metabolism controls the proliferation/differentiation balance and senescence of human primary keratinocytes. Journal of Investigative Dermatology, 139(8):1638-1647.e3. DOI: 10.1016/j.jid.2019.02.005.

3. Quek, L.S., Grasset, N., Jasmen, J.B., Robinson, K.S. and Bellanger, S*. 2018. Dual role of the Anaphase Promoting Complex/Cyclosome in regulating stemness and differentiation in human primary keratinocytes. Journal of Investigative Dermatology, 138(8):1851-1861. DOI: 10.1016/j.jid.2018.02.033.


Contact us

For more information on the SKIN AGEING Programme, please contact Dr. Leah Vardy, Dr. Oliver Dreesen, and Dr. Sophie Bellanger