Can regulating cellular aging mitigate both cancer and heart disease?

The link between cellular aging and disease development is a key point of convergence where Houston Methodist researchers are developing an intervention that can slow or perhaps even reverse the progression of both cancer and cardiovascular disease (CVD). While research in the fields of CVD and cancer has made considerable advancements in prevention, screening and treatment, these diseases continue to be the leading causes of death across the world. Researchers at Houston Methodist have made a surprising discovery leading to the development of technology with the ability to rejuvenate human cells. Risk factors common to both diseases include smoking, obesity, older age, diabetes, gender, family history, hypertension, sedentary lifestyle, unhealthy diets and the gut microbiome. This extensive list of shared risk factors suggests a commonality in the biology and pathophysiology of the two diseases. Often, CVD and cancer co-exist in the same individuals. Patients with CVD are at an elevated risk of developing cancer, and conversely, those with cancer (particularly lung, breast and colon cancer) are at a higher risk of developing CVD. Research on cancer and CVD development has demonstrated senescence – the process of biological aging – to be a common link in the connection between these two disease progressions. Senescence (derived from the Latin word “senex” meaning “old”) was originally discovered serendipitously by Leonard Hayflick in 1961 when human fibroblast cells were irreversibly arrested in cell culture after serial passaging. At the cellular level, replicative senescence (RS), characterized by telomere shortening, is induced when cells reach the end of their replicative potential and enter a state of permanent growth arrest without apoptosis. RS is dependent on a biological clock. On the other hand, stress-induced premature senescence (SIPS) is triggered by cellular stressors such as DNA damage, smoking, diabetes mellitus, as well as cancer treatments. RS and SIPS differ in both molecular mechanisms as well as timeframes; the latter occurring within three to 10 days of exposure to the insults. Albeit in a state of cell cycle arrest, senescent cells can remain metabolically active and secrete cytokines, chemokines, growth factors and reactive oxygen species (ROS). This phenotype, referred to as the senescence-associated secretory phenotype (SASP), is induced by myriad stressors, including cancer treatments, pro-inflammatory cytokines and ROS. Although the precise role of senescence in the intersection of CVD and cancer development is unclear, SASP is hypothesized to be involved.