Age-Related Changes of the Eyelid

  • Janos Feher
  • Zsolt Olah
Part of the Aging Medicine book series (AGME)


Changes of the orbicular muscle and its connective tissue play a central role in the aging of the eyelid. Age-related changes of orbicular muscle comprise a decrease of muscular fibers and a disorganization of banding structures (appearance of nemaline bodies, Z-line streaming, cytoplasmic bodies, and Z-line doubling). Mitochondria, particularly in the subsarcolemmal area, showed either a decrease in number and loss of cristae, or enlargement and proliferation of cristae. In combination with both alterations, intramitochondrial crystal formation and altered succinyl-dehydrogenase activity were also a frequent observation. Tubular aggregates originated from the sarcoplasmic reticulum and various sarcoplasmic inclusions were also observed. Intramuscular connective tissue density increased with age, and it was associated with increased glycation of collagen fibers. Neither of these alterations are considered specific for aging, but their particular combination may be responsible for the development of well-known, age-related changes and diseases of the eyelid. In addition, these data may give further information to the pathology of sarcopenia—a devastating age-related muscle disease.


eyelid aging orbicular muscle nemaline body Z-line streaming cytoplasmic body mitochondria creatine kinase crystal succinyl-dehydrogenase sarcoplasmic reticulum tubular aggregates electron microscopy 


  1. 1.
    Stefanyszyn MA, Hidayat AA, Flanagan JC (1985) The histopathology of involutional ectropion. Ophthalmology Jan. 92(1):120–7Google Scholar
  2. 2.
    Feher J (1977) Myofibre abnormalities of orbicular muscle in malposition of the eyelid. Acta Morphol Acad Sci Hung. 25(4):205–18PubMedGoogle Scholar
  3. 3.
    Manners RM, Weller RO (1994) Histochemical staining of orbicularis oculi muscle in ectropion and entropion. Eye. 8 (Pt 3):332–5PubMedGoogle Scholar
  4. 4.
    Radnot M (1973) Mitochondrial crystals in muscles of a patient with spastic entropion. Am J Ophthalmol. Apr. 75(4):713–9Google Scholar
  5. 5.
    Radnot M, Follmann P (1974) Ultrastructural changes in senile atrophy of the orbicularis oculi muscle. Am J Ophthalmol. Oct. 78(4):689–99Google Scholar
  6. 6.
    Feher J (1978) Tubuloreticular structures in the orbicularis oculi muscle of the human eye. Acta Morph.Acad Sci Hung. 26:3–10Google Scholar
  7. 7.
    Sato T, Akatsuka H, Kito K, Tokoro Y, Tauchi H, Kato K (1986) Age changes of myofibrils of human minor pectoral muscle. Mech Ageing Dev. May 34(3):297–304CrossRefGoogle Scholar
  8. 8.
    Poggi P, Marchetti C, Scelsi R (1987) Automatic morphometric analysis of skeletal muscle fibers in the aging man. Anat Re. Jan. 217(1):30–4Google Scholar
  9. 9.
    Jakobsson F, Borg K, Edstrom L (1990) Fibre-type composition, structure and cytoskeletal protein location of fibres in anterior tibial muscle. Comparison between young adults and physically active aged humans. Acta Neuropathol (Berl). 80(5):459–68Google Scholar
  10. 10.
    Roth SM, Martel GF, Ivey FM, Lemmer JT, Metter EJ, Hurley BF, Rogers MA (2000) Skeletal muscle satellite cell populations in healthy young and older men and women. Anat Rec. Dec 1. 260(4):351–8CrossRefGoogle Scholar
  11. 11.
    Beregi E, Regius O (1987) Comparative morphological study of age related mitochondrial changes of the lymphocytes and skeletal muscle cells. Acta Morphol Hung. 35(3–4):219–24PubMedGoogle Scholar
  12. 12.
    Fulle S, Belia S, Di Tano G (2005) Sarcopenia is more than a muscular deficit. Arch Ital Biol. Sep. 143(3–4):229–34Google Scholar
  13. 13.
    Francis IC, Stapleton F, Ehrmann K, Coroneo MT (2006) Lower eyelid tensometry in younger and older normal subjects. Eye. Feb. 20(2):166–72CrossRefGoogle Scholar
  14. 14.
    van den Bosch WA, Leenders I, Mulder P (1999) Topographic anatomy of the eyelids, and the effects of sex and age. Br J Ophthalmol. Mar. 83(3):347–52CrossRefGoogle Scholar
  15. 15.
    Sun WS, Baker RS, Chuke JC, Rouholiman BR, Hasan SA, Gaza W, Stava MW, Porter JD (1997) Age-related changes in human blinks. Passive and active changes in eyelid kinematics. Invest Ophthalmol Vis Sci. Jan. 38(1):92–9Google Scholar
  16. 16.
    Besne I, Descombes C, Breton L (2002) Effect of age and anatomical site on density of sensory innervation in human epidermis. Arch Dermatol. Nov. 138(11):1445–50CrossRefGoogle Scholar
  17. 17.
    Peshori KR, Schicatano EJ, Gopalaswamy R, Sahay E, Evinger C (2001) Aging of the trigeminal blink system. Exp Brain Res. Feb. 136(3):351–63CrossRefGoogle Scholar
  18. 18.
    Weeks DA, Nixon RR, Kaimaktchiev V, Mierau GW (2003) Intranuclear rod myopathy, a rare and morphologically striking variant of nemaline rod myopathy. Ultrastruct Pathol. May-Jun. 27(3):151–4CrossRefGoogle Scholar
  19. 19.
    Wallgren-Pettersson C, Jasani B, Newman GR, Morris GE, Jones S, Singhrao S, Clarke A, Virtanen I, Holmberg C, Rapola J (1995) Alpha-actinin in nemaline bodies in congenital nemaline myopathy: immunological confirmation by light and electron microscopy. Neuromuscul Disord. Mar. 5(2):93–104CrossRefGoogle Scholar
  20. 20.
    Blanchard A, Ohanian V, Critchley D (1989) The structure and function of a-actinin. J Muscle Res Cell Motil 10:280-–289PubMedCrossRefGoogle Scholar
  21. 21.
    Schroder JM, Durling H, Laing N (2004) Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn). Acta Neuropathol (Berl). Sep. 108(3):250–6 [Epub 2004 Jun 24]Google Scholar
  22. 22.
    Ilkovski B, Cooper ST, Nowak K, Ryan MM, Yang N, Schnell C, Durling HJ, Roddick LG, Wilkinson I, Kornberg AJ, Collins KJ, Wallace G, Gunning P, Hardeman EC, Laing NG, North KN (2001) Nemaline Myopathy Caused by Mutations in the Muscle a-Skeletal-Actin Gene. Am J Hum Genet. Jun. 68(6):1333–43 [Epub 2001 Apr 27]CrossRefGoogle Scholar
  23. 23.
    Ryan MM, Ilkovski B, Strickland CD, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield LK, De Girolami U, Iannaccone ST, Laing NG, North KN, Beggs AH (2003) Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology. Feb 25. 60(4):665–73Google Scholar
  24. 24.
    Michele DE, Albayya FP, Metzger JM (1999) A nemaline myopathy mutation in alphatropomyosin causes defective regulation of striated muscle force production. J Clin Invest. Dec. 104(11):1575–81CrossRefGoogle Scholar
  25. 25.
    Sanoudou D, Corbett MA, Han M, Ghoddusi M, Nguyen MA, Vlahovich N, Hardeman EC, Beggs AH (2006) Skeletal muscle repair in a mouse model of nemaline myopathy. Hum Mol Genet. Sep 1. 15(17):2603–12 [Epub 2006 Jul 28]CrossRefGoogle Scholar
  26. 26.
    Chahin N, Selcen D, Engel AG (2005) Sporadic late onset nemaline myopathy. Neurology. Oct 25. 65(8):1158–64 [Epub 2005 Sep 7]CrossRefGoogle Scholar
  27. 27.
    Oumi M, Miyoshi M, Yamamoto T (2000) The ultrastructure of skeletal and smooth muscle in experimental protein malnutrition in rats fed a low protein diet. Arch Histol Cytol. 63(5):451–7PubMedCrossRefGoogle Scholar
  28. 28.
    Oumi M, Miyoshi M, Yamamoto T (2001) Ultrastructural changes and glutathione depletion in the skeletal muscle induced by protein malnutrition. Ultrastruct Pathol. Nov-Dec. 25(6):431–6CrossRefGoogle Scholar
  29. 29.
    Hikida RS, Staron RS, Hagerman FC, Sherman WM, Costill DL (1983) Muscle fiber necrosis associated with human marathon runners. J Neurol Sci. May 59(2):185–203CrossRefGoogle Scholar
  30. 30.
    Farrants GW, Hovmoller S, Stadhouders AM (1988) Two types of mitochondrial crystals in diseased human skeletal muscle fibers. Muscle Nerve. Jan. 11(1):45–55CrossRefGoogle Scholar
  31. 31.
    Schnyder T, Winkler H, Gross H, Eppenberger HM, Wallimann T (1991) Crystallization of mitochondrial creatine kinase. Growing of large protein crystals and electron microscopic investigation of microcrystals consisting of octamers. J Biol Chem. Mar 15. 266(8):5318–22Google Scholar
  32. 32.
    Hanzlikova V, and Schiaffino S (1977) Mitochondrial changes in ischemic skeletal muscle. J. Ultrastuct. Res. 60:121–133CrossRefGoogle Scholar
  33. 33.
    Speer O, Back N, Buerklen T, Brdiczka D, Koretsky A, Wallimann T, Eriksson O (2005) Octameric mitochondrial creatine kinase induces and stabilizes contact sites between the inner and outer membrane. Biochem J. Jan 15. 385(Pt 2):445–50Google Scholar
  34. 34.
    Beregi E, Regius O, Huttl T, Gobl Z (1988) Age-related changes in the skeletal muscle cells. Z Gerontol. Mar-Apr. 21(2):83–6Google Scholar
  35. 35.
    Trounce I, Byrne E, Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet. Mar 25. 1(8639):637–9CrossRefGoogle Scholar
  36. 36.
    Lee CM, Lopez ME, Weindruch R, Aiken JM (1998) Association of age-related mitochondrial abnormalities with skeletal muscle fiber atrophy. Free Radic Biol Med. Nov 15. 25(8):964–72CrossRefGoogle Scholar
  37. 37.
    Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J Physiol. Jul 1. 526 Pt 1:203–10Google Scholar
  38. 38.
    Toyoshima C, Nakasako M, Nomura H, Ogawa H (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6A resolution. Nature. June 8. 405(6787):647–55Google Scholar
  39. 39.
    Franzini-Armstrong, C (1999) The sarcoplasmic reticulum and the control of muscle contraction. FASEB J. 13 (Suppl.), S266–S270PubMedGoogle Scholar
  40. 40.
    Pavlovicova M, Novotova M, Zahradnik I (2003) Structure and composition of tubular aggregates of skeletal muscle fibres. Gen Physiol Biophys. Dec. 22(4):425–40Google Scholar
  41. 41.
    Chevessier F, Marty I, Paturneau-Jouas M, Hantai D, Verdiere-Sahuque M (2004) Tubular aggregates are from whole sarcoplasmic reticulum origin: alterations in calcium binding protein expression in mouse skeletal muscle during aging. Neuromuscul Disord. Mar. 14(3):208–16CrossRefGoogle Scholar
  42. 42.
    Chevessier F, Bauche-Godard S, Leroy JP, Koenig J, Paturneau-Jouas M, Eymard B, Hantai D, Verdiere-Sahuque M (2005) The origin of tubular aggregates in human myopathies. J Pathol. Nov. 207(3):313–23CrossRefGoogle Scholar
  43. 43.
    Vielhaber S, Schroder R, Winkler K, Weis S, Sailer M, Feistner H, Heinze HJ, Schroder JM, Kunz WS (2001) Defective mitochondrial oxidative phosphorylation in myopathies with tubular aggregates originating from sarcoplasmic reticulum. J Neuropathol Exp Neurol. Nov. 60(11):1032–40Google Scholar
  44. 44.
    Chevessier F, Marty I, Paturneau-Jouas M, Hantai D, Verdiere-Sahuque M (2004) Tubular aggregates are from whole sarcoplasmic reticulum origin: alterations in calcium binding protein expression in mouse skeletal muscle during aging. Neuromuscul Disord. Mar. 14(3):208–16CrossRefGoogle Scholar
  45. 45.
    Narayanan N, Jones DL, Xu A, Yu JC (1996) Effects of aging on sarcoplasmic reticulum function and contraction duration in skeletal muscles of the rat. Am J Physiol. Oct. 271(4 Pt 1): C1032–40Google Scholar
  46. 46.
    Boncompagni S, d'Amelio L, Fulle S, Fano G, Protasi F (2006) Progressive disorganization of the excitation-contraction coupling apparatus in aging human skeletal muscle as revealed by electron microscopy: a possible role in the decline of muscle performance. J Gerontol A Biol Sci Med Sci. Oct. 61(10):995–1008Google Scholar
  47. 47.
    Goebel HH, Bornemann A (1993) Desmin pathology in neuromuscular diseases. Virchows Arch B Cell Pathol Incl Mol Pathol. 64(3):127–35PubMedCrossRefGoogle Scholar
  48. 48.
    Wanschit J, Nakano S, Goudeau B, Strobel T, Rinner W, Wimmer G, Resch H, Jaksch M, Akiguchi I, Vicart P, Budka H (2002) Myofibrillar (desmin-related) myopathy: clinico-pathological spectrum in 3 cases and review of the literature. Clin Neuropathol. Sep-Oct. 21(5):220–31Google Scholar
  49. 49.
    Stojkovic T, Maurage CA, Moerman A, Hurtevent JF, Krivosic-Horber R, Pellissier JF, Vermersch P (2001) Congenital myopathy with central cores and fingerprint bodies in association with malignant hyperthermia susceptibility. Neuromuscul Disord. Sep. 11(6–7):538–41CrossRefGoogle Scholar
  50. 50.
    Kjaer M (2004) Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev. Apr. 84(2):649–98Google Scholar
  51. 51.
    DeBacker CM, Putterman AM, Zhou L, Holck DE, Dutton JJ (1998) Age-related changes in type-I collagen synthesis in human eyelid skin. Ophthal Plast Reconstr Surg. Jan. 14(1):13–6CrossRefGoogle Scholar
  52. 52.
    Twigg SM, Chen MM, Joly AH, Chakrapani SD, Tsubaki J, Kim H-S, Oh R, and Rosenfeld RG (2001) Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor binding protein related protein 2) in human fibroblasts: a potential mechanism for expansion of extracellular matrix in diabetes mellitus. Endocrinology 142:1760–1769PubMedCrossRefGoogle Scholar
  53. 53.
    Visser M, Kritchevsky SB, Newman AB, Goodpaster BH, Tylavsky FA, Nevitt MC, Harris TB (2005) Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study. Am J Clin Nut. Sep. 82(3):531–7Google Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Janos Feher
    • 1
  • Zsolt Olah
    • 2
  1. 1.Nutripharma Hungaria Ltd.BudapestHungary
  2. 2.School of Sport MedicineSemmelweis UniversityBudapestHungary

Personalised recommendations