Aging is the greatest risk factor for Alzheimer’s disease. One potential culprit driving age-associated pathologies are senescent cells (ScCs). Cellular senescence refers to the phenomenon by which normal cells stop dividing. These cells accumulate with advancing age and are found at the locations of dysfunction in age-related diseases.
It is thought that senescent cells are not simply innocent bystanders and may in fact be driving tissue deterioration. One proposed mechanism for the involvement of senescent cells is the acquisition of a senescence-associated secretory phenotype, SASP. This condition refers to a state where senescent cells produce and secrete a variety of growth factors and pro-inflammatory cytokines. Senescent cells have been shown to shorten life and actively drive age-related neurodegeneration in mice; along with neurofibrillary tangles and amyloid beta plaques, Alzheimer’s patients have exhibited increased indicators of cellular senescence. Treating mice to prevent senescent cell accumulation decreased tau-dependent degeneration and cognitive decline. With the potential for senescent cell pharmacological modulation on the horizon, it is imperative to determine whether removal of senescent cells in Alzheimer’s mouse models has a beneficial impact.