Targeting pro-senescence mitogen activated protein kinase (Mapk) enzymes with bioactive natural compounds

Abstract Aging is a multifactorial universal process characterized by a gradual decrease in physiological and biochemical functions. Given that life expectancy is on the rise, a better understanding of molecular mechanisms of the aging process is necessary in order to develop anti-aging interventions. Uncontrolled cellular senescence promotes persistent inflammation and accelerates the aging process by decreasing tissue renewal, repair and regeneration. Senescence of immune cells, immunesenescence, is another hallmark of aging. Targeting pro-senescent enzymes increases survival and therefore the lifespan. Although the upregulation of Mitogen Activated Protein Kinases (MAPK) enzymes in aging is still controversial, increasing evidence shows that dysregulation of those enzymes are associated with biological processes that contribute to aging such as irreversible senescence. In this manuscript components of the MAPK pathway will be summarized, including extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38, as well as natural flavonoids, phenolic and diterpenoids with anti-senescence activity that shows positive effects on longevity and MAPK inhibition. Although more studies using additional aging models are needed, we suggest that these selected natural bioactive compounds that regulate MAPK enzymes and reduce senescent cells can be potentially used to improve longevity and prevent/treat age-related diseases.