SIRTUINS SUMMARY
Many recently discovered genes, known by such cryptic names as daf-2, pit-1,
amp-1, clk-1 and p66Shc, have been found to affect stress resistance and life
span in laboratory organisms, suggesting that they could be part of a fun-
damental mechanism for surviving adversity. The focus will be on SIR2
SIR STANDS FOR SILENT INFORMATION
REGULATOR
■ Genes that control an organism’s ability to withstand adversity
cause changes throughout the body that render it temporarily
supercharged for survival.
■ Activated over the long term, this stress response prolongs life
span and forestalls disease in a wide range of organisms.
■ Sirtuins are a family of genes that may be master regulators of
this survival mechanism.
Yeast cells age due to ribosomal DNA instability, a mother cell
accumalates extrachromasomal rDNA circles in the nucleus that have
been popped out the genome.
Copyng ERCs needs so much resources that she is no longer able to
replicate her own genome.
The SIR2 gene encodes the SIR2 enzyme with a completely novel
activity. Cellular DNA is wrapped around a complex of packaging
proteins called histones. These bear chemical tags, such as acetyl
groups, that determine how snugly the histones package DNA.
Removing acetyl groups from histones tightens the packaging further
and renders the DNA inaccessible to the enzymes responsible for
popping the rDNA circles out of the chromosome.
This deacetylated form of DNA is said to be silent because any genes
in these regions of the genome are rendered inaccessible to being
activated. Sir2 enzymes were already known to be involved in gene
silencing.
Sir2 is one of several enzymes that remove acetyl tags from the
histones, but it was discovered that its unique in that its enzymatic
activity was dependent on NAD+, which has long been known as a
conduit of many metabolic reactions in cells. This assocation between
, Sir2 and NAD was exciting due to how it linked Sir2 to metabolism as
well as how diet is linked to aging seen in calorie restriction.
THE CALORIE CONNECTION IN SIR2
restricting an animal’s calorie intake is the most famous intervention one
absolutely proven to work. The restricted regime typically involves
reducing an individual’s food consumption by 30 to 40 percent compared
with what is considered normal for its species.
The phenomenon was long attributed to a simple slowing down of
metabolism— cells’ production of energy from fuel molecules—and
therefore reduction of its toxic by-products in response to less food.
But this view now appears to be incorrect.
Calorie restriction does not slow metabolism
calorie restriction is a biological stressor like natural food scarcity
that induces a defensive response to boost and supercharge the
organism’s chances of survival. its effects include changes in cellular
defenses, repair, energy production and activation of programmed cell
death known as apoptosis.
In yeast, restricting food availability affects two pathways that
increase Sir2 enzymatic activity in the cells. On one hand, calorie
restriction turns on a gene called PNC1, which produces a
nicotinamidase that rids cells of nicotinamide, a small molecule similar
to vitamin B3 that normally represses Sir2. Consistent with the idea
that calorie restriction is a stressor that activates a survival
response, PNC1 is also stimulated by other mild stressors known to
extend yeast life span, such as increased temperature or excessive
amounts of salt.
A second pathway induced in yeast by restricted calories is respiration
which creates NAD as a by-product while lowering levels of NADH. It
turns out that not only does NAD activate Sir2 NADH is an inhibitor of
Sirt2 enzyme, so altering the cell’s NAD/NADH ratio greatly influences
Sir2 activity.
However, fanatic dieting is not a reasonable option.
,
Many recently discovered genes, known by such cryptic names as daf-2, pit-1,
amp-1, clk-1 and p66Shc, have been found to affect stress resistance and life
span in laboratory organisms, suggesting that they could be part of a fun-
damental mechanism for surviving adversity. The focus will be on SIR2
SIR STANDS FOR SILENT INFORMATION
REGULATOR
■ Genes that control an organism’s ability to withstand adversity
cause changes throughout the body that render it temporarily
supercharged for survival.
■ Activated over the long term, this stress response prolongs life
span and forestalls disease in a wide range of organisms.
■ Sirtuins are a family of genes that may be master regulators of
this survival mechanism.
Yeast cells age due to ribosomal DNA instability, a mother cell
accumalates extrachromasomal rDNA circles in the nucleus that have
been popped out the genome.
Copyng ERCs needs so much resources that she is no longer able to
replicate her own genome.
The SIR2 gene encodes the SIR2 enzyme with a completely novel
activity. Cellular DNA is wrapped around a complex of packaging
proteins called histones. These bear chemical tags, such as acetyl
groups, that determine how snugly the histones package DNA.
Removing acetyl groups from histones tightens the packaging further
and renders the DNA inaccessible to the enzymes responsible for
popping the rDNA circles out of the chromosome.
This deacetylated form of DNA is said to be silent because any genes
in these regions of the genome are rendered inaccessible to being
activated. Sir2 enzymes were already known to be involved in gene
silencing.
Sir2 is one of several enzymes that remove acetyl tags from the
histones, but it was discovered that its unique in that its enzymatic
activity was dependent on NAD+, which has long been known as a
conduit of many metabolic reactions in cells. This assocation between
, Sir2 and NAD was exciting due to how it linked Sir2 to metabolism as
well as how diet is linked to aging seen in calorie restriction.
THE CALORIE CONNECTION IN SIR2
restricting an animal’s calorie intake is the most famous intervention one
absolutely proven to work. The restricted regime typically involves
reducing an individual’s food consumption by 30 to 40 percent compared
with what is considered normal for its species.
The phenomenon was long attributed to a simple slowing down of
metabolism— cells’ production of energy from fuel molecules—and
therefore reduction of its toxic by-products in response to less food.
But this view now appears to be incorrect.
Calorie restriction does not slow metabolism
calorie restriction is a biological stressor like natural food scarcity
that induces a defensive response to boost and supercharge the
organism’s chances of survival. its effects include changes in cellular
defenses, repair, energy production and activation of programmed cell
death known as apoptosis.
In yeast, restricting food availability affects two pathways that
increase Sir2 enzymatic activity in the cells. On one hand, calorie
restriction turns on a gene called PNC1, which produces a
nicotinamidase that rids cells of nicotinamide, a small molecule similar
to vitamin B3 that normally represses Sir2. Consistent with the idea
that calorie restriction is a stressor that activates a survival
response, PNC1 is also stimulated by other mild stressors known to
extend yeast life span, such as increased temperature or excessive
amounts of salt.
A second pathway induced in yeast by restricted calories is respiration
which creates NAD as a by-product while lowering levels of NADH. It
turns out that not only does NAD activate Sir2 NADH is an inhibitor of
Sirt2 enzyme, so altering the cell’s NAD/NADH ratio greatly influences
Sir2 activity.
However, fanatic dieting is not a reasonable option.
,
