Determination of chronological aging parameters in epidermal keratinocytes by in vivo harmonic generation microscopy

Skin aging is an important issue in geriatric and cosmetic dermatology. To quantitatively analyze changes in keratinocytes related to intrinsic aging, we exploited a 1230 nm-based in vivo harmonic generation microscopy, combining second- and third-harmonic generation modalities. 52 individuals (21 men and 31 women, age range 19–79) were examined on the sun-protected volar forearm. Through quantitative analysis by the standard algorithm provided, we found that the cellular and nuclear size of basal keratinocytes, but not that of granular cells, was significantly increased with advancing age. The cellular and nuclear areas, which have an increase of 0.51 μm2 and 0.15 μm2 per year, respectively, can serve as scoring indices for intrinsic skin aging.

[1]  Brian Seed,et al.  Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation , 2003, Nature Medicine.

[2]  Egbert Lenderink,et al.  Characterization of age-related effects in human skin: A comparative study that applies confocal laser scanning microscopy and optical coherence tomography. , 2004, Journal of biomedical optics.

[3]  M. Oshimura,et al.  Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium. , 2002, The Journal of investigative dermatology.

[4]  A. Klingelhutz,et al.  The role of telomeres in the ageing of human skin , 2011, Experimental dermatology.

[5]  Toyohiko Yatagai,et al.  In vivo three-dimensional birefringence analysis shows collagen differences between young and old photo-aged human skin. , 2008, The Journal of investigative dermatology.

[6]  S. Rattan.  50 Aging of Skin Cells in Culture , 2010 .

[7]  Howard I Maibach,et al.  Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity , 2005, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[8]  Chi-Kuang Sun,et al.  Higher harmonic generation microscopy of in vitro cultured mammal oocytes and embryos. , 2008, Optics express.

[9]  Chi-Kuang Sun,et al.  Compact fiber-delivered Cr:forsterite laser for nonlinear light microscopy. , 2005, Journal of biomedical optics.

[10]  Chi-Kuang Sun,et al.  In vivo optical virtual biopsy of human oral mucosa with harmonic generation microscopy , 2011, Biomedical optics express.

[11]  Chi‐Kuang Sun,et al.  Multiphoton confocal microscopy using a femtosecond Cr:Forsterite laser , 2006 .

[12]  Chi-Kuang Sun,et al.  In vivo harmonic generation biopsy of human skin. , 2009, Journal of biomedical optics.

[13]  Y. Barrandon,et al.  Cell size as a determinant of the clone-forming ability of human keratinocytes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Giovanni Pellacani,et al.  Skin aging: in vivo microscopic assessment of epidermal and dermal changes by means of confocal microscopy. , 2013, Journal of the American Academy of Dermatology.

[15]  Gniadecka,et al.  Quantitative evaluation of chronological ageing and photoageing in vivo: studies on skin echogenicity and thickness , 1998, The British journal of dermatology.

[16]  A. Haake,et al.  Apoptosis: a role in skin aging? , 1998, The journal of investigative dermatology. Symposium proceedings.

[17]  N A Fenske,et al.  Structural and functional changes of normal aging skin. , 1986, Journal of the American Academy of Dermatology.

[18]  A. Fabre,et al.  Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy , 2005, Nature Methods.

[19]  Wilson,et al.  3D microscopy of transparent objects using third‐harmonic generation , 1998, Journal of microscopy.

[20]  F. Bregegere,et al.  Aged keratinocyte phenotyping: Morphology, biochemical markers and effects of Dead Sea minerals , 2008, Experimental Gerontology.

[21]  K. König,et al.  Keratinocyte morphology of human skin evaluated by in vivo multiphoton laser tomography , 2011, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[22]  Chi‐Kuang Sun,et al.  In Vivo Virtual Biopsy of Human Skin by Using Noninvasive Higher Harmonic Generation Microscopy , 2010, IEEE Journal of Selected Topics in Quantum Electronics.

[23]  F. Woringer.  [Aging of the skin]. , 1951, Strasbourg medical.

[24]  J. Uitto,et al.  Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin , 2002, Experimental dermatology.

[25]  P. Matts,et al.  The distribution of melanin in skin determined in vivo , 2007, The British journal of dermatology.

[26]  B. Gilchrest,et al.  Skin aging and photoaging: an overview. , 1989, Journal of the American Academy of Dermatology.

[27]  Karsten König,et al.  In vivo assessment of human skin aging by multiphoton laser scanning tomography. , 2006, Optics letters.

[28]  Karsten König,et al.  Morphological skin ageing criteria by multiphoton laser scanning tomography: non‐invasive in vivo scoring of the dermal fibre network , 2008, Experimental dermatology.

[29]  Tsang,et al.  Optical third-harmonic generation at interfaces. , 1995, Physical review. A, Atomic, molecular, and optical physics.

[30]  T. Brenn,et al.  Fitzpatrick’s Dermatology in General Medicine , 2007 .

[31]  Gail Jenkins,et al.  Molecular mechanisms of skin ageing , 2002, Mechanisms of Ageing and Development.

[32]  P. Elsner,et al.  Intrinsic and extrinsic factors in skin ageing: a review , 2008, International journal of cosmetic science.

[33]  M. Sugimoto,et al.  Telomere length of the skin in association with chronological aging and photoaging. , 2006, Journal of dermatological science.