Latent herpesviruses correlate with steeper age-related escalation of circulating fibrosis- and senescence-associated biomarkers in phenotypically normal women
July 17
Blood-based indicators of systemic fibrotic drift and waning regenerative capacity are increasingly proposed for population-level surveillance of tissue ageing in otherwise healthy adults. Here we quantified serum concentrations of five such biomarkers—procollagen type I N-terminal propeptide (PINP), procollagen type III N-terminal propeptide (PIIINP), the PIIINP/PINP ratio, phosphorylated SMAD2 (pSMAD2), and phosphorylated SMAD3 (pSMAD3)—and determined IgG seropositivity for six persistent human herpesviruses (HHV1-6) in 345 samples collected across successive visits from 167 phenotypically normal women aged 26–98 years. All markers except the PIIINP/PINP ratio rose significantly with age, with steeper trajectories in HHV-seropositive individuals. For the biomarkers, the magnitude of age-related increase ranked PINP > PIIINP > pSMAD3 > pSMAD2, whereas for the viruses the effect ranked HHV4 > HHV6 > HHV1 > HHV2 > HHV5 (HHV3 seropositivity was universal). On average, the normalized slope of biomarker escalation was 2.15-fold higher in HHV-seropositive than in seronegative groups (P = 0.003, paired-sample t-test). The presence of a common telomerase reverse transcriptase risk allele (TERT*) exerted no significant influence on these rates. These observations link prior herpesviral infection to accelerated rise of circulating indicators of fibrosis and cellular senescence, bolstering the hypothesis that HHVs contribute to age-associated decline in regenerative homeostasis, independent of TERT* genetic status.