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Intractable Rare Dis Res. 2018 Nov;7(4):229-235. doi: 10.5582/irdr.2018.01092.

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

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Division of Anti-ageing and Longevity Sciences, Department of Medical Technology, Faculty of Medical Engineering, Toin University of Yokohama, Yokohama, Japan.
Department of Orthopaedics & Rheumatology, East Medical Center, Tokyo Women's Medical University, Tokyo, Japan.
Division of Rheumatology, Nerima Hikarigaoka Hospital, Tokyo, Japan.
Department of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
School of Public Health, Teikyo University, Tokyo, Japan.
Department of Life Sciences, School of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Japan.


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.


Aging; CRP; Cytomegalovirus; Herpes virus; Inflammageing; MMP-9; Werner syndrome

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