cron-web.org

[A1CR]

We noted this report last week:
http://tinyurl.com/po327

The following appears to be an update for the CR hearing
protection story.
Hearing loss is a substantial disease in our family for
males. Do still you
hear? The involvement of Sirt1 in CR-mediated hearing
retention with age
was of note.

Someya S, Yamasoba T, Weindruch R, Prolla TA, Tanokura M.
Caloric restriction suppresses apoptotic cell death in the
mammalian cochlea
and leads to prevention of presbycusis.

Neurobiol Aging. 2006 Aug 3; [Epub ahead of print]
PMID: 16890326 http://tinyurl.com/l8y6p

http://en.wikipedia.org/wiki/Presbycusis ... hair
cells or spiral
ganglion (SG) cells in the cochlea. Here we show that
caloric restriction
suppresses apoptotic cell death in the mouse cochlea and
prevents late onset
of presbycusis. Calorie restricted (CR) mice, which
maintained body weight
at the same level as that of young control (YC) mice,
retained normal
hearing and showed no cochlear degeneration. ... middle-age
control (MC)
mice. ... our findings suggest that loss of critical cells
through apoptosis
is an important mechanism of presbycusis in mammals, and
that CR can retard
this process by suppressing apoptosis in the inner ear tissue.

... 23% of people aged between 65 and 75 years of age,
and 40% of
people over 75 years of age have presbycusis [
http://tinyurl.com/puuog ],
... C57BL/6 mice ... 4-month-old young control group
(YC), a
15-month-old control group (MC), and a 15-month-old
calorie-restricted group
(CR). .... we reduced the caloric intake of B6 mice to 74%
of that fed to
control animals in early adulthood (2 months of age), and
this dietary
regimen was maintained until 15 months of age. ... The mean
weight of 15
month-old CR mice was significantly lower than that of 15
month-old MC mice
(p < 0.05, n = 6) [~30 vs 40 g] ... not different from the
mean weight of 4
month-old YC mice, indicating that the CR diet maintained
the weight of 15
month-old CR mice at the same level as that of YC mice ...
YC mice exhibited
normal hearing; however by 15 months, MC mice exhibited
significant
age-related hearing loss (Fig. 2). In contrast, CR mice
displayed normal
hearing [equla or better than YC mice] ... exhibited
significant loss of SG
cells and hair cells throughout the cochlea (Fig. 3B and E).
Notably, CR
prevented these degenerative changes (Fig. 3C and F). YC
mice also
demonstrated no degeneration of SG cells or hair cells (Fig.
3A and D). ...

... Of the 45,037 genes studied, 3666 genes (8.1%)
were significantly
up-regulated, and 4275 genes (9.5%) were significantly
down-regulated in CR
compared to MC mice ... (P value <0.05 and fold change
>1.1). A comparison
of cochleae from YC and MC mice revealed that 199 genes
(0.44%) were
significantly up-regulated, and 284 genes (0.63%) were
significantly
down-regulated in MC compared to YC mice ... (P value <0.05
and fold change
>1.1). ... molecular events associated with CR and aging
in the cochlea, we
selected the following major functional categories of genes:
programmed cell
death, mitochondrion, energy pathways, proteolysis and
peptidolysis,
response to stress, cytoskeleton, cell adhesion,
extracellular matrix,
neurophysiological process, synaptic transmission,
neuropeptide signaling
pathway, synapse, perception of sound, and DNA repair,
because these
functional categories of genes are thought to be associated
with apoptotic
cell death or cochlear degeneration. ... Summaries of gene
expression
changes associated with apoptotic cell death in the cochlea
of aging mice
and its prevention by CR are given in a global view in Table
1. ...

Table 1.
Global view of transcriptional changes associated with
apoptotic cell death
in the cochlea Biological process categories
=====================================
CR Aging---TN
N FC N FC---
=====================================
Apoptotic cell death 24 -3 +254
Mitochondrial function
Mitochondrion 137 +8 -484
Energy pathways 28 +1 -91
Proteolysis and peptidolysis 49 -8 +457
Response to stress 59 -2 +403
Cell structural modulation
Cytoskeleton 69 +4 -440
Cell adhesion 57 -1 +425
Extracellular matrix 25 +3 -237
Neurophysiological function
Neurophysiological process 25 +2 -246
Synaptic transmission 15 +1 -107
Neuropeptide signaling pathway 5 +1 -66
Synapse 8 +2 -51
Inner ear function, Perception of Sound 8 +*ND 30
DNA repair 11 +*ND 98
=====================================
N, the number of identified genes in the category; FC,
fold change; TN,
the total number of genes in the category on the GeneChip;
*ND, not
detected.

... Our findings indicate that CR can suppress
cochlear apoptosis. ...
CR up-regulated the expression of 165 genes involved in
mitochondrial
function, suggesting that mitochondrial function was
maintained under
conditions of CR. Previous studies have shown that CR delays
accumulation of
mtDNA mutations [2], and reduces mitochondria-mediated
apoptotic pathways
[3] and [32]. Taken together, these findings suggest that CR
may suppress
mitochondrial apoptotic pathways by slowing down
accumulation of mtDNA
mutations. ... Our DNA microarray and quantitative RT-PCR
results indicated
that CR induced Sirt1 in the cochlea. Sirt1, a NAD-dependent
protein
deacetylase, inhibits p53-dependent apoptosis by suppressing
acetylated p53
[18] and [38]. Thus, these findings raise the possibility
that CR may
suppress p53-dependent apoptosis by inducing Sirt1 in the
cochlea. In
summary, our findings suggest that loss of critical,
irreplaceable cells
through apoptosis may be a major factor in the development
of presbycusis in
mammals, and that CR can protect critical cochlear cells by
inhibiting
apoptosis. Furthermore, our findings provide strong evidence
that CR or
staying lean can reduce the risk for presbycusis in mammals.