“Mitochondrial Oasis Effect”: fasting => NAD+ up in mitos => cell survival

Quick storytelling through citations (alert from Jim Hardy, thanks):

Cell: Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival

A major cause of cell death caused by genotoxic stress is thought to be due to the depletion of NAD+ from the nucleus and the cytoplasm. Here we show that NAD+ levels in mitochondria remain at physiological levels following genotoxic stress and can maintain cell viability even when nuclear and cytoplasmic pools of NAD+ are depleted. Rodents fasted for 48 hr show increased levels of the NAD+ biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD+. Increased Nampt provides protection against cell death and requires an intact mitochondrial NAD+ salvage pathway as well as the mitochondrial NAD+-dependent deacetylases SIRT3 and SIRT4. We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis.

Scientific American: Eat (Less) to Live (Longer)

Researchers report in the journal Cell that the phenom is likely linked to two enzymes—SIRT3 and SIRT4—in mitochondria (the cell’s powerhouse that, among other tasks, converts nutrients to energy). They found that a cascade of reactions triggered by lower caloric intake raises the levels of these enzymes, leading to an increase in the strength and efficiency of the cellular batteries. By invigorating the mitochondria, SIRT3 and SIRT4 extend the life of cells, by preventing flagging mitochondria from developing tiny holes (or pores) in their membranes that allow proteins that trigger apoptosis, or cell death, to seep out into the rest of the cell.

“We didn’t expect that the most important part of this pathway was in the mitochondria,” says David Sinclair, an assistant professor of pathology at Harvard Medical School and a study co-author. “We think that we’ve possibly found regulators of aging.”

And last, the interesting personal background of the principal investigator David A. Sinclair (see also: Resveratrol goes to the clinic: a Pulitzer for David Stipp!) from the recent Technology Review portrait, The Enthusiast:

Sinclair says his bravado and drive come from his grandmother Vera, who fled to Australia in the wake of the failed 1956 revolution in her native Hungary. Her son, David’s father, changed the family name from Szigeti. “My grandmother is the black-sheep rebel of the family,” he says. “She gave birth to my dad at age 15 in 1939 – imagine the scandal then – and has lived with natives in New Guinea and eaten human flesh,among other things. She once got in trouble with the police for being the first person to wear a bikini on a Sydney beach. She’s a 60s bohemian who helped raise me and taught me how to think differently and question dogma.”