Faulty mitochondria are already heavily implicated in the aging process, but they’re now connected to a newly discovered form of cellular senescence too.
A new type of senescence
Cellular senescence was previously thought to be caused by genotoxic stress and damage, but hadn’t been connected specifically to the mitochondria. Senescence is a mechanism the body uses to ‘quarantine’ at risk cells, preventing them from dividing. These cells then sit around, essentially as ‘old’ cells, spewing out various chemicals to their neighbours. As we accumulate more senescent cells, they are believed to contribute to the aging process – driving inflammation across the body and facilitating cancer growth.
“We don’t yet know how much this process contributes to natural aging, but we do think the findings are important in addressing mitochondrial diseases, and those age-related diseases, such as some forms of Parkinson’s, which involve mitochondrial dysfunction.”
More than just free-radical damage
The new discovery came while researchers were observing what happened when a class of proteins called Sirtuins were eliminated. These play a key repair role in cells, and are associated with longevity. When the team specifically eliminated mitochondrial versions of these, they surprisingly found the cells quickly became senescent and stopped dividing. They also released different signals to ‘normal’ senescent cells, displaying an entirely new type of senescence they termed MiDAS – mitochondrial dysfunction-associated senescence.
This dysfunction had a knock on effect on NAD+ levels. NAD+ is a key cellular substrate mitochondria require to produce energy for the cell, and it is widely believed dwindling levels of NAD+ contribute to the aging process by affecting energy sensing pathways. Interestingly, the senescence was specifically induced by this deletion, rather than free-radical damage.
“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.”
In mice engineered to develop a disease called Progeria in response to mitochondrial damage, in which many aging processes speed up, they also found these unique, mitochondrially associated senescent cells. These MiDAS cells seemed to suppress adipogenesis – the creation of new fat cells. This potentially explains why patients can experience fat loss in response to certain drugs that deplete mitochondria or damage them.
“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.”
Considering both cellular senescence and dysfunctional mitochondria are two of the major hallmarks of aging biology, this is a really fascinating development that reveals more about senescent cell variations.
Read more at Neuroscience News
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