Aging-associated latent herpes viral infection in normal Japanese individuals and patients with Werner syndrome

Abstract

Human aging is probably controlled by a combination of intrinsic/genetic factors including metabolism/ catabolism functions (1), and extrinsic/environmental factors such as infections (2). The possible intrinsic/ genetic factors include genetically-determined progeroid syndrome genes such as WRN for Werner syndrome (WS) (3). WS has been proposed as the representative human natural ageing model. Because patients with WS, transmitted autosomal-recessively by the homozygous mutation of WRN (RecQ3 DNA helicase), usually manifest their premature aging phenotypes immediately after adulthood. Typical aging signs and symptoms in WS include voice change, bilateral cataracts, gray hair/alopecia, skin atrophy, skin pigmentation, type II diabetes mellitus, central obesity, atherosclerosis, hyperlipidemia, skin ulcer, renal dysfunction, osteoporosis, and cancer/sarcoma. The Summary A series of our "inflammageing" study examining serum samples from a maximum of 217 healthy Japanese individuals aged between 1 and 100 years and mutation-proven 40 patients with Werner syndrome (WS) indicated normal aging-associated elevations of highly sensitive CRP (hsCRP) and matrix metalloproteinase-9 (MMP-9). To further study the contribution of environmental factors such as persistent herpes viral infection to inflammageing, IgG antibodies against varicella/zoster virus (VZV) and cytomegalovirus (CMV) were examined in the same serum samples as has been done for hsCRP and MMP-9 analyses. The mean levels of serum IgG viral antibodies were comparable between normal (mean ± SE: 31.0 ± 4.3 unit) and WS (38.6 ± 7.6) for CMV, and between normal (42.0 ± 12.2) and WS (29.8 ± 3.8) for VZV, respectively. Significant associations of aging with IgG anti-CMV antibody were in normal aging (p = 0.023) and WS (p = 0.037), but not with IgG VZV in both conditions. Aging-associated change of IgG anti-CMV antibody titer in WS increased significantly (1.32 times higher) compared with normal aging (p = 0.037). IgG anti-CMV level was significantly elevated in the male gender than female in both conditions (p = 0.006). Elevated hsCRP level was significantly associated with IgG anti-CMV (p = 0.016) and IgG anti-VZV (p = 0.008) antibodies in normal aging, but not in WS. Serum MMP-9 was significantly associated with IgG anti-CMV level (p = 0.0002) in normal aging, but not in WS. Persistent herpes viral infection may constitute a part of "inflammageing" in normal aging and WS.