Elixer Of Old Age

The indigenous people of the Ryukyu Islands have, it seems, the elixir of old age.  They live on average for 110 years.

They longevity has been tied to their eating habits, and termed the Okinawa diet by commercial interests.  The islanders consume only 1 calorie per gram of food, primarily through green and yellow vegetables, grains and very little sugar.  Essentially, they are eating a nutrient-rich, low-calorie diet that triggers a stress response within their cells.

The years of low calorie consumption leads to a long, healthy life, say the proponents of the diet.  A recent article by Dr. Sandy Westerheide and colleagues in the journal Science provides support for this theory, although in organisms several orders of magnitude less complex than humans.

The nematode Caenorhabditis elegans responds similar to human cells in times of calorie restriction.  Within the millions of cells that make up the tiny nematode, there are specific pathways that act in concert to keep the organism going.

In response to stress such as reduced calorie intake, the cells adapt by changing their pathways, according to Dr. Westerheide.  They do so in tiny increments that, in the way of life, have amplified results—in this case, increased longevity.

The key players in the pathway that get changed are highly conserved proteins that are the master controllers of the microscopic world of the cell.

They are called transcription factors.  They tell the cell whether to grow, divide, fight invaders, specialize, or commit suicide.  Their functions are as ubiquitous in humans as the nematode, although small differences in sequence may exist.

Dr. Westerheide focused on two proteins, the enzyme sirtuin 1 (SIR1) that increases the production of the second protein, heat shock factor 1 (HSF1).  Both increase in concentration within cells when the body consumes fewer calories.

The ultimate result is an increase in HSF1 production.  This protein works entirely by binding to DNA, and sending signals that promote growth.

In aging individuals, there is less SIR1, and in the absence of this protein, HSF1 can no longer bind DNA.  There is no growth.  Instead, there is aging, and eventually, death.

But in an individual who meticulously controls his or her calorie consumption, a stress response is triggered.  These responses, learnt early in evolution, are protective mechanisms that allow cells to remain alive in the face of harsh conditions—thermal stress faced by single-celled bacteria on hot sulfur springs, oxygen toxicity faced by the lung cells of scuba divers, and calorie restriction faced by cells in Ryukyu islanders.

In the nematode, the stress response increases the levels of SIR1.  This leads to increased binding by HSF1 to DNA, leading to growth signals even in an aging cell.

That is the secret of the long life of the healthy nematode.  Whether HSF1 has a part in the response in higher organisms remains to be seen, but SIR1 looks important.

And given that cancer cells have strong stress responses, Dr. Westerheide’s work indicates a role for HSF1 in forming tumors, something that has been hinted at already by other researchers.

Small proteins have big roles in the elixir of the Ryukyu islanders.