“What are ‘zombie‘ cells?”
“As we age, these damaged cells start to accumulate and cause sterile inflammation which can alter metabolism and stem cell function, promoting aging and the conditions that are often associated with it, like Alzheimer’s disease. These zombie cells are formally called, senescent cells. When the cells get to a certain level of damage, they go through an aging process of their own called cellular senescence. When cells become damaged or if they replicate too many times, they undergo a process of irreversible removal from the cell cycle and start releasing inflammatory factors that stimulate the immune response to clear the damaged cells. A younger person’s immune system is healthy and is able to clear the damaged cells, but as people age, they aren’t cleared as effectively and they accumulate causing potential problems.”
“Senescent cells display a “zombie”-like behavior known as a senescence-associated secretory phenotype (SASP). In this death-defying, zombie-like state, the cells ramp up their release of proteins, bioactive lipids, DNA, and other factors that, like a zombie virus, induce nearby healthy cells to join in the dysfunction.”
“Could killing off these ‘zombie‘ cells in the mice delay their premature descent into old age? The answer was yes. In a 2011 study, the team found that eliminating these ‘senescent‘ cells forestalled many of the ravages of age. The discovery set off a spate of similar findings. In the seven years since, dozens of experiments have confirmed that senescent cells accumulate in ageing organs, and that eliminating them can alleviate, or even prevent, certain illnesses (see ‘Becoming undead’). This year alone, clearing the cells in mice has been shown to restore fitness, fur density and kidney function. It has also improved lung disease and even mended damaged cartilage. And in a 2016 study, it seemed to extend the lifespan of normally aging mice.”
“To date about a dozen drugs have been reported that can mop up zombie cells. Clearance of the cells in mice has been shown to delay or alleviate everything from frailty to cardiovascular dysfunction to osteoporosis to, most recently, neurological disorders – though whether killing senescent cells extends life is complicated. Most of the benefit seen in mice seems to be in extending healthspan, the time free of frailty or disease, and as a result median lifespan (being sick, after all, is risky). True longevity – the maximum time the animals remain alive for – remains relatively unchanged, though studies published in July and September 2018 show an extension of remaining lifespan in mice that were treated when they were very old.”
Zombie cells are the ones that can’t die but are equally unable to perform the functions of a normal cell. These zombie, or senescent, cells are implicated in a number of age-related diseases. “Senescent cells are known to accumulate with advancing natural age and at sites related to diseases of aging, including osteoarthritis; atherosclerosis; and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s,” says Darren Baker, Ph.D., a Mayo Clinic molecular biologist and senior author of the paper. “In prior studies, we have found that elimination of senescent cells from naturally aged mice extends their healthy life span.”
Mayo Clinic researchers and their collaborators have shown that when senescent cells — also known as “zombie cells” — are removed from fat tissue in obese mice, severity of diabetes and a range of its causes or consequences decline or disappear.
Inflammation and dysfunction of fat tissue cause some of the insulin resistance in obese people. In many cases, that dysfunction is caused by zombie cells that already have been shown to be responsible for conditions related to aging and illness, including osteoporosis, muscle weakness, nerve degeneration and heart disease. These cells also accumulate in the fat tissues of obese and diabetic people and mice.
In this study, the researchers, using genetically modified mice and wild-type (normal) mice, removed zombie cells two ways: by causing genetically-mediated cell death and by administering a combination of senolytic drugs. Senolytic drugs selectively kill senescent cells but not normal cells. The result: Glucose levels and insulin sensitivity improved. The mice also showed a decline in inflammatory factors and a return to normal fat cell function.
Briefly, cellular senescence is a process whereby cells stop dividing and go through phenotypic changes, such as secretome and chromatin changes in addition to tumor-suppressor activation. Senescent cells accumulate in several organs as we grow older, are involved in tissue dysfunction and implicated in numerous pathologies such as cancer. Therefore, they are generally considered to be a “hallmark” of aging and have earned the nickname “zombie” cells.
Cellular senescence allows the stressed cell to survive, but the cell may become like a zombie, functioning abnormally and secreting substances that kill cells around it. “When cells enter this stage, they change their genetic programming and become pro-inflammatory and toxic,” said study senior author Miranda E. Orr, Ph.D. She is a VA research health scientist at the South Texas Veterans Health Care System, faculty member of the Sam and Ann Barshop Institute for Longevity and Aging Studies, and instructor of pharmacology at UT Health San Antonio. “Their existence means the death of surrounding tissue.” The team reported the discovery in the journal Aging Cell. To clear senescent cells from the brains of middle-aged mice with advanced brain disease, researchers used a combination of drugs called senolytics.