Ekdanai Uawithya

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that culminates in inflammation, neuronal degeneration and loss of nerve functioning. While there is no specific cause of MS, there are factors that can influence disease progression, in particular tobacco smoke exposure (smoking). Smoking has been shown to increase inflammation, disease activity, and disability progression – herein we aim to connect this to both early inflammation and late-stage neurodegeneration. We propose that smoking enhances immune cell aging (immunosenescence) and examine evidence showing that this induces immune cell phenotypes that mirror physiological aging, specifically the depletion of naïve T-cell pools and the expansion of terminally differentiated, senescent CD8+ populations. We also review literature that suggests potential mechanism(s), including oxidative stress, cholenergic signaling, and epigenetic remodeling. By integrating clinical and mechanistic studies, we provide a framework that suggests smoking-associated immune aging shifts the MS profile from acute relapses toward sustained, treatment-resistant disability – and that smoking cigarettes is an active driver of disease, not just an environmental risk factor.