Rejuvenative Outcomes for the Lip and Eye Area

  • Giuseppe MonfrecolaEmail author
  • Matteo Megna


Elderly population is constantly growing worldwide. In order to reduce or counteract the signs of human skin aging, massive surgical and nonsurgical aesthetic and cosmetic procedures have been developed. In this context, the face, particularly in the perioral and the periorbital regions, usually represents the body area where the signs of skin aging initially appear, becoming more evident as time goes by. The mechanisms of skin aging are complex, as much as the number of the different skin structures involved. Therefore, a deep knowledge of the mechanisms underlying skin aging is needed in order to counteract correctly and effectively the different signs of skin aging through the use of appropriate and harmless interventions.


Reactive Oxygen Species Production Elastic Fiber Skin Aging Orbicularis Muscle Wrinkle Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Extracellular matrix






Matrix metalloproteinases


Reactive oxygen species


Tumor necrosis factor


Ultraviolet rays




  1. 1.
    American Society of Aesthetic Plastic Surgery (2006) 11.5 million cosmetic procedures in 2005. Accessed 02 Sep 2015
  2. 2.
    Baier J, Maisch T, Maier M et al (2006) Singlet oxygen generation by UVA light exposure of endogenous photosensitizers. Biophys J 91:1452–1459CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Balzani A, Chilgar RM, Nicoli M et al (2013) Novel approach with fractional ultrapulse CO2 laser for the treatment of upper eyelid dermatochalasis and periorbital rejuvenation. Lasers Med Sci 28:1483–1487CrossRefPubMedGoogle Scholar
  4. 4.
    Bernhard D, Moser C, Backovic A et al (2007) Cigarette smoke-an aging accelerator? Exp Gerontol 42:160–165CrossRefPubMedGoogle Scholar
  5. 5.
    Birkedal-Hansen H (1987) Catabolism and turnover of collagens: collagenases. Methods Enzymol 144:140–171CrossRefPubMedGoogle Scholar
  6. 6.
    Brandt FS, Cazzaniga A (2008) Hyaluronic acid gel fillers in the management of facial aging. Clin Interv Aging 3:153–159CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Centers for Disease Control and Prevention (CDC) (2003) Trends in aging United States and worldwide. MMWR Morb Mortal Wkly Rep 52:101–104Google Scholar
  8. 8.
    Christensen K, Doblhammer G, Rau R et al (2009) Ageing populations: the challenges ahead. Lancet 374:1196–1208CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chung JH, Yano K, Lee MK et al (2002) Differential effects of photoaging vs intrinsic aging on the vascularization of human skin. Arch Dermatol 138:1437–1442PubMedGoogle Scholar
  10. 10.
    Chung JH, Eun HC (2007) Angiogenesis in skin aging and photoaging. J Dermatol 34:593–600CrossRefPubMedGoogle Scholar
  11. 11.
    Coleman SR, Grover R (2006) The anatomy of the aging face: volume loss and changes in 3-dimensional topography. Aesthet Surg J 26:S4–S9CrossRefPubMedGoogle Scholar
  12. 12.
    Dahmane R, Poljsak B (2011) Free radicals and intrinsic skin aging: basic principles. Health Med 5:1647–1654Google Scholar
  13. 13.
    Dai G, Freudenberger T, Zipper P et al (2007) Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol 171:1451–1461CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Davis EC, Callender VD (2011) Aesthetic dermatology for aging ethnic skin. Dermatol Surg 37:901–917CrossRefPubMedGoogle Scholar
  15. 15.
    Desai S, Upadhyay M, Nanda R (2009) Dynamic smile analysis: changes with age. Am J Orthod Dentofacial Orthop 136:310–311CrossRefPubMedGoogle Scholar
  16. 16.
    Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Erbagci I, Erbagci H, Kizilkan N et al (1994) The effect of age and gender on the anatomic structure of Caucasian healthy eyelids. Am J Ophthalmol 117:231–234CrossRefGoogle Scholar
  18. 18.
    Farage MA, Miller KW, Elsner P et al (2008) Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosmet Sci 30:87–95CrossRefPubMedGoogle Scholar
  19. 19.
    Fisher GJ, Wang ZQ, Datta SC et al (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337:1419–1428CrossRefPubMedGoogle Scholar
  20. 20.
    Fisher GJ, Kang S, Varani J et al (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138:1462–1470CrossRefPubMedGoogle Scholar
  21. 21.
    Friedman O (2005) Changes associated with the aging face. Facial Plast Surg Clin North Am 13:371–380CrossRefPubMedGoogle Scholar
  22. 22.
    Furnas DW (1978) Festoons of orbicularis muscle as a cause of baggy eyelids. Plast Reconstr Surg 61:540–546CrossRefPubMedGoogle Scholar
  23. 23.
    Furnas DW (1993) Festoons, mounds, and bags of the eyelids and cheek. Clin Plast Surg 20:367–385PubMedGoogle Scholar
  24. 24.
    Giardini MA, Segatto M, da Silva MS et al (2014) Telomere and telomerase biology. Prog Mol Biol Transl Sci 125:1–40CrossRefPubMedGoogle Scholar
  25. 25.
    Gilchrest BA (1989) Skin aging and photoaging: an overview. J Am Acad Dermatol 21:610–613CrossRefPubMedGoogle Scholar
  26. 26.
    Gilchrest BA (1996) A review of skin ageing and its medical therapy. Br J Dermatol 135:867–875CrossRefPubMedGoogle Scholar
  27. 27.
    Gilchrest BA (2013) Photoaging. J Invest Dermatol 133:E2–E6CrossRefPubMedGoogle Scholar
  28. 28.
    Goh C (2009) The need for evidence-based aesthetic dermatology practice. J Cutan Aesthet Surg 2:65–71CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gonzalez-Ulloa M, Flores ES (1965) Senility of the face: basic study to understand its causes and effects. Plast Reconstr Surg 36:239–246CrossRefPubMedGoogle Scholar
  30. 30.
    Goodsell DS (2001) The molecular perspective: ultraviolet light and pyrimidine dimers. Stem Cells 19:348–349CrossRefPubMedGoogle Scholar
  31. 31.
    Grozdev IS, Van Voorhees AS, Gottlieb AB et al (2011) Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 65:537–545CrossRefPubMedGoogle Scholar
  32. 32.
    Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460CrossRefPubMedGoogle Scholar
  33. 33.
    Heck DE, Vetrano AM, Mariano TM et al (2003) UVB light stimulates production of reactive oxygen species: unexpected role for catalase. J Biol Chem 278:22432–22436CrossRefPubMedGoogle Scholar
  34. 34.
    Herrmann G, Wlaschek M, Lange TS et al (1993) UVA irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts. Exp Dermatol 2:92–97CrossRefPubMedGoogle Scholar
  35. 35.
    Hussein MR (2005) Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 32:191–205CrossRefPubMedGoogle Scholar
  36. 36.
    Ichihashi M, Fujiwara Y (1981) Clinical and photobiological characteristics of Japanese xeroderma pigmentosum variant. Br J Dermatol 105:1–12CrossRefPubMedGoogle Scholar
  37. 37.
    Ichihashi M, Ueda M, Budiyanto A et al (2000) UV-induced skin damage. Toxicology 189:21–39CrossRefGoogle Scholar
  38. 38.
    Inomata S, Matsunaga Y, Amano S et al (2003) Possible involvement of gelatinases in basement membrane damage and wrinkle formation in chronically ultraviolet B-exposed hairless mouse. J Invest Dermatol 120:128–134CrossRefPubMedGoogle Scholar
  39. 39.
    Iovine B, Nino M, Irace C et al (2009) Ultraviolet B and A irradiation induces fibromodulin expression in human fibroblasts in vitro. Biochimie 91:364–372CrossRefPubMedGoogle Scholar
  40. 40.
    Jenkins G (2002) Molecular mechanisms of skin ageing. Mech Ageing Dev 123:801–810CrossRefPubMedGoogle Scholar
  41. 41.
    Kammeyer A, Luiten RM (2015) Oxidation events and skin aging. Ageing Res Rev 21:16–29CrossRefPubMedGoogle Scholar
  42. 42.
    Kang S, Fisher GJ, Voorhees JJ (2001) Photoaging: pathogenesis, prevention, and treatment. Clin Geriatr Med 17:643–659CrossRefPubMedGoogle Scholar
  43. 43.
    Kjellén L, Lindahl U (1991) Proteoglycans: structures and interactions. Annu Rev Biochem 60:443–475CrossRefPubMedGoogle Scholar
  44. 44.
    Kondo S (2000) The roles of cytokines in photoaging. J Dermatol Sci 23:S30–S36CrossRefPubMedGoogle Scholar
  45. 45.
    Kurban RS, Bhawan J (1990) Histologic changes in skin associated with aging. J Dermatol Surg Oncol 16:908–914CrossRefPubMedGoogle Scholar
  46. 46.
    Landau M (2007) Exogenous factors in skin aging. Curr Prob Dermatol 35:1–13CrossRefGoogle Scholar
  47. 47.
    Lee DE, Chung MY, Lim TG et al (2013) Quercetin suppresses intracellular ROS formation, MMP activation, and cell motility in human fibrosarcoma cells. J Food Sci 78:1464–1469CrossRefGoogle Scholar
  48. 48.
    Li T, Ning K, Le J et al (2012) Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 149:1269–1283CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Love LP, Farrior EH (2010) Periocular anatomy and aging. Facial Plast Surg Clin North Am 18:411–417CrossRefPubMedGoogle Scholar
  50. 50.
    Mera SL, Lovell CR, Jones RR et al (1987) Elastic fibres in normal and sun-damaged skin: an immunohistochemical study. Br J Dermatol 117:21–27CrossRefPubMedGoogle Scholar
  51. 51.
    Millis AJ, Hoyle M, McCue HM et al (1992) Differential expression of met- alloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts. Exp Cell Res 201:373–379CrossRefPubMedGoogle Scholar
  52. 52.
    Muto J, Kuroda K, Wachi H et al (2007) Accumulation of elafin in actinic elastosis of sun-damaged skin: elafin binds to elastin and prevents elastolytic degradation. J Invest Dermatol 127:1358–1366CrossRefPubMedGoogle Scholar
  53. 53.
    Naylor EC, Watson RE, Sherratt MJ (2011) Molecular aspects of skin ageing. Maturitas 69:249–256CrossRefPubMedGoogle Scholar
  54. 54.
    Ortonne JP (2002) Photoprotective properties of skin melanin. Br J Dermatol 146:7–10CrossRefPubMedGoogle Scholar
  55. 55.
    Oxlund H, Andreassen TT (1980) The roles of hyaluronic acid, collagen and elastin in the mechanical properties of connective tissues. J Anat 131:611–620PubMedPubMedCentralGoogle Scholar
  56. 56.
    Perkins SW, Sandel HD 4th (2007) Anatomic considerations, analysis, and the aging process of the perioral region. Facial Plast Surg Clin North Am 15:403–407CrossRefPubMedGoogle Scholar
  57. 57.
    Pfeifer GP, You YH, Besaratinia A (2005) Mutations induced by ultraviolet light. Mutat Res 571:19–31CrossRefPubMedGoogle Scholar
  58. 58.
    Poljsak B, Dahmane RG, Godic A (2012) Intrinsic skin aging: the role of oxidative stress. Acta Dermatovenerol Alp Panon Adriat 21:33–36Google Scholar
  59. 59.
    Pons B, Belmont AS, Masson-Genteuil G et al (2010) Age-associated modifications of Base Excision Repair activities in human skin fibroblast extracts. Mech Ageing Dev 131:661–665CrossRefPubMedGoogle Scholar
  60. 60.
    Rinnerthaler M, Bischof J, Streubel MK et al (2015) Oxidative stress in aging human skin. Biomolecules 5:545–589CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Scharffetter-Kochanek K, Brenneisen P, Wenk J et al (2000) Photoaging of the skin from phenotype to mechanisms. Exp Gerontol 35:307–316CrossRefPubMedGoogle Scholar
  62. 62.
    Shapiro DP (1999) Geriatric demographics and the practice of otolaryngology. Ear Nose Throat J 78:418–421PubMedGoogle Scholar
  63. 63.
    Situm M, Buljan M, Cavka V et al (2010) Skin changes in the elderly people-how strong is the influence of the UV radiation on skin aging? Coll Antropol 34:9–13PubMedGoogle Scholar
  64. 64.
    Sjerobabski-Masnec I, Situm M (2010) Skin aging. Acta Clin Croat 49:515–518PubMedGoogle Scholar
  65. 65.
    Starcher B, Conrad M (1995) A role for neutrophil elastase in solar elastosis. Ciba Found Symp 192:338–346PubMedGoogle Scholar
  66. 66.
    Truswell WH 4th (2013) Aging changes of the periorbita, cheeks, and midface. Facial Plast Surg 29:3–12CrossRefPubMedGoogle Scholar
  67. 67.
    Tsutsumi M, Denda M (2007) Paradoxical effects of beta-estradiol on epidermal permeability barrier homeostasis. Br J Dermatol 157:776–779CrossRefPubMedGoogle Scholar
  68. 68.
    Varani J, Schuger L, Dame MK et al (2004) Reduced fibroblast interaction with intact collagen as a mechanism for depressed collagen synthesis in photodamaged skin. J Invest Dermatol 122:1471–1479CrossRefPubMedGoogle Scholar
  69. 69.
    Warren R, Gartstein V, Kligman AM et al (1991) Age, sunlight, and facial skin: a histologic and quantitative study. J Am Acad Dermatol 25:751–760CrossRefPubMedGoogle Scholar
  70. 70.
    Wlaschek M, Tantcheva-Poor I, Naderi L et al (2001) Solar UV irradiation and dermal photoaging. J Photochem Photobiol 63:41–51CrossRefGoogle Scholar
  71. 71.
    Wollina U (2013) Perioral rejuvenation: restoration of attractiveness in aging females by minimally invasive procedures. Clin Interv Aging 8:1149–1155CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Woodley DT, Kalebec T, Banes AJ et al (1986) Adult human keratinocytes migrating over nonviable dermal collagen produce collagenolytic enzymes that degrade type I and type IV collagen. J Invest Dermatol 86:418–423CrossRefPubMedGoogle Scholar
  73. 73.
    Yaar M, Gilchrest BA (2012) Aging of the skin. In: Goldsmith LA, Katz SI, Gilchrest BA et al (eds) Fitzpatrick’s dermatology in general medicine. McGra Hill, New York, pp 1213–1226Google Scholar
  74. 74.
    Zouboulis CC, Chen WC, Thornton MJ et al (2007) Sexual hormones in human skin. Horm Metab Res 39:85–95CrossRefPubMedGoogle Scholar
  75. 75.
    Zouboulis CC, Makrantonaki E (2011) Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol 29:3–14CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Section of Dermatology, Department of Clinical Medicine and SurgeryUniversity of Naples Federico IINaplesItaly

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