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Death by garbage

This “garbage-accumulation theory” has gotten fresh support from scientists who experimented with cells whose internal garbage-removal systems were blocked.

Several theories of why we get old are under consideration by scientists, another popular one being that DNA damage accumulates over a lifetime and kills us. 

Some of the theories overlap, and many researchers believe more than one could be correct; so the statement that one theory has gotten new support doesn’t necessarily disprove other theories or invalidate past research.

But the findings could shed light on a key aspect of the aging problem, and help suggest possible future anti-aging therapies, according to Yuri Stroikin of Linköping University, Linköping, Sweden, and colleagues. The team conducted one recent study that they said supported the garbage accumulation theory.

The theory holds that aging is the result of years of accumulated damage to molecules important for our bodies’ functioning. The molecules suffer damage largely as a result of power-generating structures in each cell called mitochondria, which—not unlike man-made power plants—can produce harmful chemicals in addition to life-sustaining energy.

These chemicals, called free radicals, can wreak havoc on DNA and other vital molecular structures inside the cell. Cells are not helpless in the face of this damage; they have DNA-repair mechanisms as well as systems for sweeping out the damaged material to make room for fresh replacements.

But these sweeping systems don’t operate with perfect efficiency. The result is an accumulation of damaged molecules that are under-efficient or altogether worthless—molecular “garbage.” 

According to the garbage-accumulation theory, this refuse builds up until it starts seriously getting in the way of cellular business, if not actively doing harm on its own. Eventually it reaches “a critical level incompatible” with life, Stroikin’s team wrote in a paper published in the January issue of the research journal Biogerontology.

In the paper, Stroikin and his research team described experiments they had done on cells treated with a chemical that blocks their internal garbage-removal system, called autophagy. This treatment led to an accumulation of “garbage” and sharply raised the chances that any given cell would die as time progressed, the researchers found. 

However, the treatment wasn’t harmful to cells that were given space to constantly reproduce by division, the team found. This was also consistent with the theory, they added, because it holds that one way cells can evade death by garbage is by continuously dividing. 

Cell division staves off the onslaught of trash by distributing the debris evenly between the two daughter cells, halving each cell’s garbage load.

But an organism’s cells don’t divide forever. After an animal reaches adulthood, cell division slows down. This is when the problem begins, according to the garbage-accumulation theory.

“Our results indicate that biological ‘garbage’ is, indeed, deleterious for cells and finally kills them if accumulates in large enough quantities,” Stroikin and colleagues wrote. A weakness of the study, he acknowledged, is that individual cells are only a model of the aging process, not the real process itself.

An important component of biological garbage is a thought to be a substance called lipofuscin, a brownish pigment left over from the body’s breakdown and cleanup of damaged blood cells. Being a plastic-like material, lipofuscin is hard for the body to break down. 

Lipofuscin builds up inside the heart of the body’s garbage-disposal system itself: tiny sacs of digestive enzymes in each cell called lysosomes, which are in effect cellular garbage bags.

In a more recent study, scientists  found that quicker lipofuscin accumulation was associated with shorter lifespans in roundworms, creatures often used as a research model for basic molecular life processes. 

Thus the buildup specifically characterizes “a physiologically aged state rather than simply marking chronological time,” the researchers, with Rutgers University in Piscataway, N.J., wrote in a paper describing their findings. The paper appeared in the June issue of the research journal Aging Cell.

Stroikin and colleagues wrote that “accumulation of such biological ‘garbage’ seems to upset normal cellular functions, resulting in decreased adaptability and finally in cell death. Cell division is apparently a natural anti-ageing mechanism.”

Strokin and his team suggested that the garbage-accumulation theory also fits with the fact that one of the few scientifically well-established ways to delay aging is by nearly going on a near-starvation diet. This “caloric restriction” extends lifespans by roughly 35 percent to 65 percent in mice, a 1986 study found.

The prolonged fasting characteristic of caloric-restriction diets leads to an increase in autophagy, the garbage removal process. This is consistent with the garbage accumulation theory, because it predicts better garbage removal would increase lifespans, Stroikin and colleagues pointed out.

That caloric restriction would boost autophagy makes sense because autophagy, seen from another point of view, is also a process in which the body consumes its own tissues in order to feed itself in the absence of other food. The word autophagy literally means self-eating.

These considerations may provide fodder for possible anti-aging therapies in the future, Stroikin and colleagues added; one strategy might be seeking out treatments that stimulate these cleansing processes. 

Aubrey de Grey of the University of Cambridge, U.K., has proposed that one solution might be to insert genes into the body that produce enzymes that degrade lipofuscin. Certain bacteria and fungi possess such genes. The strategy is “radical and challenging,” Stroikin and colleagues suggested, but it might work.

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