**6. Diseases caused by impaired viscoelastic properties of connective tissues**

We discuss aging-associated diseases that result in impaired physical properties of connective tissues based on a review of genetic diseases that cause impairment in the physical properties of connective tissues.

Viscoelastic Properties of the Human Dermis and

Other Connective Tissues and Its Relevance to Tissue Aging and Aging–Related Disease 167

**Figure 12.** Clinical appearance of photo-aged skin. Deep wrinkles and comedo (black dots) are observed.

**Figure 13.** Histochemical results of solar elastosis. Versican is detected by its anti-fibrillin binding region (2B1) or its anti-HA binding region (6084). HA is detected using a biotin-conjugated link protein

Based on the physical properties of skin and other connective tissues, we propose "Tarumi disease" as an aging-associated, connective tissue loosening disease. Tarumi diseases are preferentially found in the elderly population, with some exceptions. Tarumi is a Japanese word that represents tissue loosening. Aging-associated loosening of connective tissue is a major pathogenesis for emphysema, aneurysm, skin wrinkles, pelvic organ, and hernias. The Tarumi diseases that we are proposing are listed in the table below (Table 1). In 2001, an interesting association between pseudoexfoliation syndrome and abdominal aortic aneurysm was reported (28). However, it should be noted that this report has not been

supported by the subsequent studies on the prevalence of these conditions.

(biotin LP).

**8. Tarumi disease** 

Marfan syndrome (MFS) is a relatively common genetic connective tissue disease. MFS is an autosomal dominant connective tissue disease that affects the aorta, lungs, ciliary zonule, muscles, and other organs. However, most phenotypes appear only in the later stages of life. The primary cause of MFS appears to be due to mutations in the microfibrillar molecule fibrillin-1, although some phenotypes observed in various organs are believed to develop from the dysregulation of TGF-beta. One explanation for the genotype-phenotype correlation is due to the aberrant activation of TGF-beta stored within microfibrils through the binding between fibrillin-1 and LTBPs (21) (Figure 4). Recent studies have highlighted the importance of proper modulation of non-canonical TGF-beta signaling (22). The role of versican in MFS is currently unknown. Interestingly, the tissue phenotype resulting from MFS shows similarities to that of aging. For instance, aneurysm, emphysema, hernia, and muscle atrophy are all common features of MFS patients and also of elderly patients. However, the correlation between MFS and aging connective tissue phenotypes is currently unknown. MFS appears to be a model for impaired viscoelasticity of human tissues, which is discussed in the following section.
