Senescence and fibrosis in salivary gland aging and disease

Salivary gland hypofunction is highly prevalent in aged and diseased individuals leading to significant discomfort and morbidity. One factor that contributes to salivary gland hypofunction is cellular aging, or senescence. Senescent cells can impair gland function by secreting paracrine-acting growth factors and cytokines, known as senescence-associated secretory phenotype (SASP) factors. These SASP factors stimulate inflammation, propagate the senescent phenotype through the bystander effect, and stimulate fibrosis. As senotherapeutics that target senescent cells have shown effectiveness in limiting disease manifestations in other conditions, there is interest in the use of these drugs to treat salivary gland hypofunction. In this review, we highlight the contribution of senescence and fibrosis to salivary gland pathologies. We also discuss therapeutic approaches to eliminate or modulate the senescent SASP phenotype for treating age-related salivary gland diseases and extending health span.