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Disabling Reproductive Cells for a Longer Life

Disabling Reproductive Cells for a Longer Life

Disabling germ line cells may be the secret for a longer life. 

Many organisms posses germ and somatic cells, or reproductive cells and cells building the body respectively. While the somatic cells can divide a certain number of times (known as the Hayflick limit), germ cells are potentially immortal, meaning that they can keep dividing. So, from an evolutionary point of view, it makes sense to protect the germ line from damage, even if that comes with a cost for the somatic cells. This cost is aging. Then what if these germ cells can be disabled?

Less germ cells, a longer life

A new study looks into this by investigating mutants of the roundworm Caenorhabditis elegans. These mutants are temperature-sensitive and at a restrictive temperature (25°C) they don’t produce germ cells. As expected, the worms that do not produce germ cells have a lifespan up to 60% longer than their regular counterparts. By not producing a germ line, the worms can invest more in protecting their somatic tissues, leading to a longer life.

What happens is that the re-investment of resources in the somatic cell line leads to a higher proteasome activity in the somatic tissues. This means that unwanted or damaged proteins are removed more efficiently, increasing longevity. The elevated ‘cleaning activity’ is associated with an increased expression of rpn-6, a subunit of the proteasome (the protein cleaning machine).

Rpn-6 protein restores homeostasis

Based on this finding, the researchers hypothesized that this subunit is an important way to regulate the protein balance. As such, rpn-6 might potentially contribute to treat conditions that are (partially) caused by troubles with the protein homeostasis, or an imbalance in good versus bad or damaged proteins, such as Alzheimer’s, Parkinson’s and Huntington’s disease. This was tested in the worms by the expression of disease-causing proteins. When rpn-6 was overexpressed in these worms, they showed marked improvements.

So, by looking into the cause of the longevity of germ line-less tiny roundworms, researchers have found that it boosts the protein cleaning machinery. This, in turn, can be used to investigate potential ways to deal with several conditions that are characterized by a faulty protein balance, and routes to alleviate the detrimental effects of aging. The next step is to find out whether or not these results hold in mammalian models.

Reference:

Vilchez, D.; Morantte, I.; Liu, Z.; Douglas, P.M.; Merkwirth, C.; Rodrigues, A.P.C.; Manning, G. & Dillin, A. (2012). RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature. 489: 263 – 268. doi:10.1038/nature11315.

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