, Volume 18, Issue 4, pp 489–498 | Cite as

Decline of lymphatic vessel density and function in murine skin during aging

  • Sinem Karaman
  • Dorina Buschle
  • Paola Luciani
  • Jean-Christophe Leroux
  • Michael Detmar
  • Steven T. Proulx
Original Paper


Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.


Aging Lymphatic vessels Vascular leakage In vivo imaging 



The authors thank Jeannette Scholl and Carlos Ochoa for excellent technical assistance. This work was supported by Swiss National Science Foundation Grants 3100A0-108207 and 31003A-130627, Advanced European Research Council Grant LYVICAM, Oncosuisse, Krebsliga Zurich, and Leducq Transatlantic Network of Excellence on Lymph Vessels in Obesity and Cardiovascular Disease (11CVD03).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

10456_2015_9479_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1734 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Sinem Karaman
    • 1
  • Dorina Buschle
    • 1
  • Paola Luciani
    • 1
  • Jean-Christophe Leroux
    • 1
  • Michael Detmar
    • 1
  • Steven T. Proulx
    • 1
  1. 1.Institute of Pharmaceutical SciencesSwiss Federal Institute of Technology, ETH ZurichZurichSwitzerland

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