Life Extension

So how does resveratrol extend life?

Resveratrol works at the cellular level to fight diseases of aging such as cancer, heart disease, diabetes, and Alzheimer’s.  To do this, Resveratrol activates (either directly or indirectly) a class of proteins called sirtuins that are found naturally in cells.  In particular, resveratrol activates one of the seven sirtuin proteins - SIRT1.  SIRT1 fights aging at the cellular level in two ways: 1) it repairs damages (i.e. breaks) in cell’s DNA; and 2) it regulates gene expression by ensuring that genes that should be silent (“switched off”) remain silent; to do this, SIRT1 protects the molecular packaging surrounding the genes that keeps them inactive. As organisms (including humans) age, SIRT1 spends more of its time repairing damaged DNA (caused by degrading mitochondria due to aging, free radicals, and ultraviolet light) than ensuring the proper genes remain silent.  Accordingly, without the attention of SIRT1, the molecular packaging around the genes that keeps them silent begins to unravel and they eventually ‘switch on’.  For instance, a liver cell might have its pancreatic cell genes turned on while SIRT1 is busy repairing damaged DNA (as opposed to regulating gene expression).  As a result, the defective liver cells can damage the liver (note: all genes are present in all cells but the vast majority are silent). According to Dr. Phillip Oberdoerffer, who conducted the study (in the Harvard Laboratory of Dr. David Sinclair) that exhibited SIRT1’s importance in fighting cellular aging, “…we see here, through a proof-of-principal demonstration, that elements of aging can be reversed.” The results of Dr. Oberdoerffer’s experiment at the cellular level also translated into longer life at the organism level – that is, Dr. Oberdoerffer fed mice (who were genetically modified to develop lymphoma) resveratrol or administered them extra sirtuin genes – the result was that the mean lifespan of the mice increased by 24 to 46 percent.  This result is not surprising considering in past experiments resveratrol has increased the lifespan of worms, yeast fruit flies, fish, and obese mice up to 29%, 70%, 24%, 50%, and 30% respectively. Further proof that sirtuin activation increases longevity lies in the case of caloric restriction (i.e. the reduction of calories in a 'normal' diet by approximately 40% while still consuming necessary vitamins and minerals).  In 1935 scientists at Cornell discovered that caloric restriction (“CR”) increased the lifespan of mice by an average of 30-40%.  While this result was impressive, scientists did not know if CR would extend the life of primates (monkeys, humans).  This question, over 70 years in the making, was answered in 2009 when scientists at the University of Wisconsin announced the results of a study that proved CR extends the lives of monkeys.  The study, which started in 1989, began with 76 rhesus monkeys – half on a CR diet and half on a normal diet. Over the 20 years, five out of 38 monkeys on the CR diet died of age related diseases while 14 of the 38 monkeys on a normal diet died of age related diseases. Specifically, the moneys on the CR diet had no diabetes and fewer cases of heart disease and cancer.   Additionally, the monkeys on the CR diet looked much younger; that is, their coats were thicker, their eyes were not as sunken, and their posture was better. That CR increases lifespan in yeast, flies, rodents, and primates is not surprising considering MIT professor Leonard Guarente has traced the molecular pathway of CR to sirtuins.  In essence, it is believed that a sever caloric cutback signals cells that hard times are ahead and therefore the cells switch into survival mode.  In this survival mode genes focus on maintenance and repair as opposed to reproduction.  Accordingly, sirtuins are activated to (as mentioned above) repair damages cell DNA and by ensuring that genes that should be silent remain silent.

Note: in addition to activating Sirt1 (either directly or indirectly), resveratrol also activates other longevity genes including Sirt3, Sirt4, FoxO1, Foxo3a and PBEF. Science is still determining the role that these longevity genes play in the human body.

UPDATE: one recent study revealed resveratrol works by blocking phosphodiesterase enzymes (for their part, these enzymes break down cyclic AMP and regulate cell energy).   The end result is elevated levels of cyclic AMP.   Down the line, sirtuins are indirectly activated.  

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