Broadly, we know what aging is; our bodies get older as time goes on and they begin to decline in a variety of ways. From one person to another, there are huge variations in how that happens, and some people have much shorter or longer periods in which they are healthy, or differences in lifespan. But despite many years of intense research, many of the the biological mechanisms that underlie aging remain elusive and somewhat mysterious.
There are certain things that have been connected with aging cells, such as telomeres, which cap the ends of chromosomes to protect them, and get shorter with each round of cell division. Telomeres are also related to cellular senescence, in which cells stop dividing. Inflammation is also associated with the aging process, and is thought to accelerate it. Instability in DNA, the proteins that are encoded by genes, and fats, have also been linked to aging. The epigenome, proteome, and metabolome have been used to create markers of biological age.
Cellular senescence has been linked to various physiological processes and many age-related diseases. Lots of things can trigger cell senescence, like short telomeres, reactive oxygen species, UV rays, and cancer treatment, for some examples. Senescent cells also affect tissues, because they release a wide variety of molecules. This leads to what is known as the senescent associated secretory phenotype (SASP).
A new study has now explored the connections between aging, mitochondria, and apoptosis, a programmed cell death process. The findings have been reported in Nature.
Mitochondria are well known as the powerhouses of the cell. Apoptosis is not the same cell fate as cell senescence, but mitochondria are crucial to that process. When the outer membrane of mitochondria are damaged and become permeable, it causes cell death by apoptosis. This study has shown, however, that when membrane leakage happens in some mitochondria in a cell but does not lead to cell death, it is a feature of cellular senescence.
This new study has shown that in senescent cells, the membranes of mitochondria start to leak. Mitochondria are crucial energy-generators for cells, and as their DNA leaks out, cells become inflamed. This further promotes aging.
Additional work showed that if the damage to mitochondrial membranes could be prevented, inflammation stopped and health was improved during aging.
"Our work reveals a wholly unexpected link between mitochondria and the inflammatory effects of aged cells. We find that mitochondrial permeabilization, a process inextricably linked with cell death, promotes inflammation in aged and damaged cells," explained co-corresponding study author Professor Stephen Tait of the School of Cancer Sciences at the University of Glasgow. "This opens up new areas of investigation, with the exciting potential to provide new treatments for aging and cancer."
Sources: University of Glasgow, Nature
