Several factors working together help to explain why the face ages. Similar to other organs, the skin including the eyelid skin simply ages over time,¹⁰ and because sagging eyelids are considered a feature of the aging process of the skin in general,⁶,¹¹ the intrinsic (heritable) and extrinsic (nonheritable) risk factors for both conditions broadly overlap. It is a fact that age (per decade) is a major contributing factor to the development of dermatochalasis.⁵,⁶,⁸ Other risk factors include a higher basal metabolic index, a lighter skin color, female sex, solar damage, and possibly smoking.⁶,⁷,⁹ A recent epidemiological study conducted both in the Netherlands and the United Kingdom found that female sex is associated with a higher risk of mild sagging, while males have an increased risk of severe sagging.⁶ Interestingly, the same study found that smoking only had borderline relevance, and that sun exposure was not a factor contributing to the development or progression of dermatochalasis.⁶ These results are surprising because they contradict the long-held view that both cigarette smoking and sun exposure are detrimental to skin aging in general.⁵,¹²

What the results of this large level II study do suggest is that genetic or heritable factors do play a more significant role in the pathogenesis of dermatochalasis than was previously realized. One arm of this study was conducted on twins in the United Kingdom and found that heritability plays a role in the induction or prevention of dermatochalasis in 61% of patients.⁶ Genetic analysis showed that a recessive gene located on the short arm of chromosome 18 (18p11) may have a defensive role against sagging eyelids.⁶ An additional possible gene that could likely be biologically relevant to dermatochalasis is the SMYD3 gene, which is associated with matrix metalloproteinase (MMP-9) upregulation, a well-known modulator of the extracellular matrix.⁶ Another recent genetic study conducted on middle-aged French females showed that two closely located genes may have a putative role in skin photoaging: the STXBP5L gene and the FBXO40 gene.¹¹ These studies suggest that future research should be directed further toward investigating the molecular mechanisms of skin aging. It has been suggested that the inheritance of dermatochalasis resembles the inheritance pattern of other common complex traits in humans like body height, in that several DNA variants could each have a small additive or subtractive effect, ultimately determining the phenotype.⁶

Regardless of the actual role played by intrinsic or extrinsic etiologic factors, the actual events involved in the pathophysiology of dermatochalasis are not yet fully understood,¹³ but suggested mechanisms explaining how the face ages include increased skin laxity, gravitational effects, and deflation (soft tissue as well as bone), which by working together
all underwrite the senescent eyelid changes that are observed in clinical practice.

Progressive skin laxity, which is a characteristic feature of the aging ocular adnexal tissue, both in the upper and lower eyelids, probably occurs due to a triad of increased elastolysis, increased collagenolytic activity, as well as lymphostasis.¹³,¹⁴ This is supported by histopathologic findings that include an increase in the diameter and number of lymphatic vessels, a reduction in elastic fibers that are essential for the structure and function of the lymphatic system, disarrangement in collagen fibers with wide spacing between collagen bundles, stromal edema, and an increase in the number of macrophages, which suggest that subclinical inflammation may also play a role in the development or the initiation of dermatochalasis.¹³,¹⁴,¹⁵ Lymphangiectasia, or dilatation of lymphatic vessels, is an indicator of lymphostasis. The stasis of interstitial fluid, which ensues, plays a pivotal role in the development of dermatochalasis.¹³,¹⁵ Because dermal lymphatic capillaries are surrounded by an elastic network that is specialized in organizing the peristaltic activities of lymphatics, the breakdown of elastic fibers or the reduction in elastic fiber density may also play an important role in the pathogenesis of dermatochalasis,¹³,¹⁵ as well as baggy eyelids.¹³ There is also an increase in the diameter of collagen fibers and wide spacing between fibers suggesting stromal edema.¹³,¹⁵ A unique study that was published recently compared the histologic findings in the skin versus the orbicularis oculi muscle and revealed that the orbicularis muscle remains relatively intact throughout the aging process.¹⁶ As we shall see later, this is a major finding of significant clinical relevance.