A new study suggested a novel physiological role for mitochondria. Researchers found that mitochondrial dysfunction in proliferating human cells induces senescence (biological aging) and causes a distinct secretory phenotype. The research study results, which might have great importance for the study of mitochondrial diseases and age-related conditions such as Parkinson’s, were published in the journal Cell Metabolism. The article is entitled “Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype.”
Cellular senescence, an important driver of the aging process and a response usually attributed to stress and damage from extracellular and endogenous sources, is characterized by a permanent state of cellular growth arrest and loss of the ability to divide.
New research from Dr. Judith Campisi at Buck Institute for Research on Aging, and her team, indicated that signaling from dysfunctional mitochondria also induces senescence, with cells having a different senescence-associated secretory phenotype (SASP). The discovery occurred when researchers were eliminating sirtuins, proteins involved in longevity, in human cell cultures. Elimination of mitochondrial sirtuins led to a senescent phenotype with a different SASP, lacking one of the major SASP factors previously identified, the IL-1-dependent inflammatory arm, a phenomenon named by the research team as MiDAS (mitochondrial dysfunction-associated senescence). Furthermore, mitochondrial dysfunction also disrupted the balance of NAD+, an enzyme that is a co-factor of sirtuins, arresting cell growth and disrupting IL-1 dependent SASP.
Dr. Christopher Wiley, PhD, said in a news release, “The NAD+ balancing act happens outside the mitochondria in the cytoplasm of the cell. This really highlights a signaling role for mitochondria, something understudied in the context of disease. And it identifies a new type of SASP, underscoring the existence of different types of senescence.”
Studies in mice with dysfunctional mitochondria and premature aging showed an accumulation of senescent cells and suppression of adipogenesis, an important cell metabolism and fat creation mechanism. According to the researchers, these results explain the loss of subcutaneous fat and lipodystrophy, a degenerative condition of the body’s fat tissue, observed in patients taking early HIV drugs, which deplete mitochondrial DNA.
Dr. Campisi concluded, “For any disease that has a mitochondrial component, this research adds a potential explanation for the real driver of the dysfunction — and it’s not free radicals, which we ruled out in our study. Our findings suggest a new role for mitochondria when it comes to affecting physiology.”