Neuroscience & Medicine, 2013, 4, 172-180
http://dx.doi.org/10.4236/nm.2013.43028 Published Online September 2013 (http://www.scirp.org/journal/nm)
Relationship between Age and Neurogenesis in Old World
Monkeys
Tarique D. Perera1*, Arkadiy Yaretskiy2, Anna V. Rozenboym3, Zeena Audi1, Cecilia Lipira1,
Jean Tang1, Jerem y Hill1, Lakshmi Thirumangalakudi1, Daniel C. Lee4, Andrew J. Dwork1,5,
Jeremy D. Coplan2
1Departments of Psychiatry, College of Physicians and Surgeons, Columbia University Medical Center and New York State Psychi-
atric Institute, New York, USA; 2Nonhuman Primate Facility, Department of Psychiatry, SUNY Downstate Medical Center, Brook-
lyn, USA; 3Department of Biological Sciences, Kingsborough Community College, Brooklyn, USA; 4Division of Cardiothoracic
Surgery, SUNY Downstate Medical Center, Brooklyn, USA; 5Department of Molecular Imaging and Neuropathology, New York
State Psychiatric Institute, New York, USA.
Received February 12th, 2013; revised March 11th, 2013; accepted April 14th, 2013
Copyright © 2013 Tarique D. Perera et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with
increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its
most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to
age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to
precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age
were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously stud-
ied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age
and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the
dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between
age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear sig-
nificant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show
neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout
adulthood and begins to decline in middle age in bonnet macaques.
Keywords: Neurogenesis; Age; Macaca Radiate; Nonhuman Primates
1. Introduction
Neurogenesis, the birth of new neurons, occurs through-
out adulthood in the dentate gyrus of the hippocampus
[1]. The process of hippocampal neurogenesis can be
divided into several developmental steps, beginning with
the proliferation of precursor cells, their survival and
migration, and finally, their differentiation into mature
functional neurons. Newborn precursor cells arise from
the subgranular zone of the dentate gyrus and, once hav-
ing matured into granule cell neurons, and extend axonal
projections along the mossy fiber tract to the CA3 region
of the hippocampus, becoming integrated into the hippo-
campal circuitry [2-5].
With increasing age, there is a continuous decline in
precursor cell proliferation and net hippocampal neuron-
genesis that occurs in rat [6] and mouse models [7]. More
recent experimental designs using primates showed
similar results. In New World marmoset nonhuman pri-
mates, the number of bromodeoxyuridine (BrdU)-labeled
cells in the dentate gyrus was shown to decline linearly
with age [8]. To further study the relationship of neuro-
genesis and age in primates, we performed a correlation
analysis on data collected from 71 adult bonnet monkeys
obtained under the rubric of five separate studies: the
“Fluoxetine” study, the “ECS” study, the “Ziprasidone”
study and two separate “Variable Foraging Demand”
(VFD) studies (see Table 1). In contrast to earlier ex-
periments conducted in New World monkeys by other
*Corresponding author.

Relationship between Age and Neurogenesis in Old World Monkeys 173
Table 1. Summary of five different nonhuman primate studie s.
“Fluoxetine” Study
Study of the effects of fluoxetine treatment on neurogenesis in nor-
mally reared primates and subjects exposed to separation stress condi-
tions [13].
“Variable Foraging Demand” (VFD)
Study 1 and Study
VFD-reared and normally reared adolescent bonnet macaques were
exposed to a mild fear-provoking stimulus 2 years after the end of
differential rearing in order to examine the nature and persistence of
VFD rearing.
(Coplan, Andrews et al. [14]; Rosenblum et al. [15]).
“Electroconvulsive Shock”( ECS) Study Examination of whether neurogenesis is increased following electro-
convulsive shock treatment [47].
“Ziprasidone” study Effects of Ziprasidone on neurogenesis [16].
investigators [8,9], our analysis contains significantly
more subjects. Furthermore, we utilize the bonnet ma-
caque, an Old World monkey, which possesses greater
phylogenetic proximity to humans than the New World
monkeys from previous studies. The two lines are be-
lieved to have split from each other approximately 35
million years ago [10].
The bonnet macaque (Macaca radiata) is an Old World
monkey that reaches sexual maturity at 5 - 6 years of age
for males, and after about 3 years of age ± 4 months for
females [11,12]. From our experience in our colony, se-
nescence in bonnet monkeys begins at around twelve to
fourteen years. Here, we statistically analyze the rela-
tionship of age and neurogenesis, as reflected by the
number of doublecortin (DCX) expressing cells, in the
subgranular zone of the dentate gyrus in subjects ranging
from 3.5 to 17 years of age.
2. Methods
2.1. Fluoxetine Study
Socially housed adult, female bonnet macaque monkeys
were randomized into five groups: Control-Placebo (n =
3), Control-Drug (n = 3), Stress-Placebo (n = 3),
Stress-Drug (n = 5), and Radiation-Stress-Drug (n = 4).
The Control groups were exposed to non-stressful ambi-
ent conditions for 15 weeks, while the Stress groups were
exposed to chronic stress involving social isolation for 2
days a week and home-cage reunion for 5 days a week
for a total of 15 weeks. During this period, half of the
controls (Control-Drug) and half of the stressed subjects
(Stress-Drug) were administered fluoxetine in its once
weekly preparation (Prozac Weekly from Eli Lilly Co.)
at a dose of 13.5 mg/kg/week via nasogastric tubing
(NGT), while the remaining animals (Control-Placebo
and Stress-Placebo) received saline placebo also via
NGT once a week for 15 weeks. Both treatments were
administered under ketamine/xylazine sedation. The Ra-
diated-Stress-Drug (XRT) group received bilateral tem-
poral lobe gamma-irradiation (20 or 30 Gy fractionated
over 10 sessions) under ketamine/xylazine sedation daily
for two weeks. Following two weeks of rest, the XRT
group was exposed to concurrent stress and drug admini-
stration (identical to the Stress-Drug group) for 15 weeks.
All five groups were sacrificed using perfusion methods
on week 15 [13].
2.2. ECS Study
Single-housed adult male bonnet monkeys were random-
ized to two groups. The ECS group (n = 6) received 12
administrations of high dose (350% above seizure thre-
shold) brief-pulse (1.5msec) bilateral ECS under general
anesthesia (methohexital) and muscle relaxation (suc-
cinylcholine) over a 4-week period. The SHAM group (n
= 6) only received anesthesia and muscle relaxation over
this 4-week period. Four ECS, and 4 SHAM subjects
were transcardially perfused immediately following the
study (Immediate-sacrifice group) while 2 ECS and 2
SHAM were perfused 4 weeks after the completion of
treatment (Delayed-sacrifice group).
2.3. Variable Foraging Demand (VFD) Study
Single-housed adult male bonnet macaques that were
exposed to maternal variable foraging demand (VFD
group) or normal rearing [low foraging demand (LFD
group)] during infancy were sacrificed in order to exam-
ine neurogenesis rates. The VFD group consisted of adult
bonnets that were subjected to VFD for four months
during infancy (first year of life). Rearing stress stemmed
from maternal uncertainty when mother-infant dyads
were exposed to Variable Foraging Demand (VFD).
During this period, the LFD group was exposed to nor-
mal rearing conditions stemming from non-stressful for-
aging conditions. Previous studies have shown that
VFD-reared offspring manifest behavioral and biological
abnormalities reflective of mood and anxiety disorders
that persist into adulthood [14,15].
2.4. Ziprasidone Study
Single-housed female adult bonnet macaques were ran-
domized into two cohorts. The first cohort (n = 12) con-

Relationship between Age and Neurogenesis in Old World Monkeys
174
sisted of Stress-Drug (n = 3), Stress-Placebo (n = 3),
Control-Drug (n = 3) and Control-Placebo (n = 3). In the
second cohort (n = 10), all subjects were exposed to
stressful conditions. The Drug group (n = 5) received
ziprasidone whereas the control received placebo. The
control groups were exposed to non-stressful ambient
conditions while the stress group was exposed to re-
peated separation stress. The drug groups received zipra-
sidone 4.5 mg/kg daily five times/week [16].
2.5. Immunohistology
In all studies, subjects were sacrificed by transcardiac
saline perfusions and the brains were immediately ex-
tracted and post-fixed. The left hippocampus was sec-
tioned into 40 µm free floating slices using a freezing
microtome and stored in 40 wells with cryoprotectant
and sodium azide (NaN3) at 20˚C. These sections were
immuno-labeled to detect neurogenesis and different
stages of neuronal maturation. Immature neurons were
indicated by the expression of doublecortin (DCX). The
age of DCX-expressing neurons is based on data gener-
ated in rodent studies [17]. In nonhuman primates, DCX-
expressing cells with analogous morphology seem to be
2 - 3 fold older [18-20]. For example, DCX-expressing
neurons with mature dendritic morphology (stage 3) may
be 8-12 weeks old in the monkey.
Raters blinded to treatment condition counted all
DCX-expressing cells in the subgranular zone (SGZ) of
the dentate gyrus. To enable counting of cell clusters, the
cells are examined at ×100 magnification under oil im-
mersion, omitting cells in the outermost focal plane. The
densities of labeled cells are calculated by dividing the
total number of cells counted by the volume of SGZ, at
that level (outlined area × 40 µm). In order to generate
true density, we divided the total number of cells identi-
fied by the total volume examined. The total number of
stained cells, in contrast to the density, is relatively im-
pervious to the effects of swelling or shrinkage of tissues.
In order to determine the total number of cells identified,
we employed systematic uniform random sampling, so
that all rostrocaudal levels have an equal chance of being
counted and assuring that no tissue was lost.
2.6. Statistical Analyses
The first step was to generate means and standard devia-
tions of the five different studies that were used for the
examination of the relationship between age and neuro-
genesis for neurogenesis rates, age and body weight. The
studies were compared using a one-way ANOVA and
compared individually using post-hoc Newman-Keuls
testing. Sex distribution for the overall study was as-
sessed using a Chi-square analysis. Significant effects
were to be used as a control variable in subsequent gen-
eral linear models. Because each of the five studies were
performed within a single sex, there was a confound be-
tween study and sex. Thus, sex could not be used as a
factor when the study was used and separate general lin-
ear models were implemented. A final factor, coding
whether or not a subject was an experimental control,
was used for the general linear models. This factor was
used to control for any potential bias introduced by ef-
fects on neurogenesis induced by experimental manipu-
lation.
For continuous measures analyses, univariate correla-
tions were performed using Pearson’s Correlation Coef-
ficient regressing age versus neurogenesis and weight
versus neurogenesis. To follow up the latter analysis, a
Pearson’s Correlation Coefficient was performed only in
the control subjects to demonstrate that the relationship
between age and neurogenesis was not dependent on
potential bias introduced by experimental subjects.
A general linear model was then employed using dou-
blecortin (DCX) labeling as the dependent variable, en-
tering study and experimental status (control versus
non-control) as categorical variables, and age and weight
as continuous predictor variables. Sex could not be ex-
amined in this model as it was confounded by study.
Therefore, a second general linear model was performed
where study number was omitted as a variable and sex
was included as a categorical variable.
For categorical measures analyses, the subjects were
split into two age groups with the median age of <9 years
of age as the “younger” group and 9 years or greater for
the “older” group. The median split would correspond to
middle adulthood in humans. The two groups were com-
pared by t-tests and then Pearson’s correlations were
performed in each group separately.
Probability values were deemed significant at p ≤ 0.05,
two-tailed. Standard deviation was taken into account
throughout all analyses.
3. Results
As a first step, we examined the means and standard de-
viations of the doublecortin staining rates for the five
different studies that were used for the examination of
the relationship between age and neurogenesis. As can be
observed in Table 2, there is a marked difference be-
tween studies [F(4;67) = 4.24; p = 0.004].
On post-hoc Newman-Keuls analysis, it was revealed
that the “ziprasidone” group exhibited neurogenesis rates
that were significantly reduced in comparison to the
“ECS” group and the “VFD1” group (p < 0.05). “Study”
was therefore used as a covariate for general linear
analyses.
A similar significant effect was noted for age in that
the ziprasidone study exhibited increases in age versus
the remaining subjects (Post-hoc Newman-Keuls: p <

Relationship between Age and Neurogenesis in Old World Monkeys
175
Table 2. Means and standard deviations for five different nonhuman primate studies on neurogenesis, age, and weight.
Study-Means ± Sd Doublecortin¹ *Age² - Weight³ -
“Fluoxetine” (N = 18) 97.2 ± 76.2 9.7 ± 3.0 5.1 ± 1.4
“ECS” (N = 8)* 136.6 ± 138 7.3 ± 0.5 7.91 ± 0.9
“Ziprasidone” (N = 21) 20.1 ± 26.9 13.6 ± 2.1 5.8 ± 1.2
“VFD1” (N = 8) 114.1 ± 93.3 8.8 ± 1.8 10.4 ± 2.9
“VFD2” (N = 17) 68 ± 96.3 9.6 ± 2.5 7.5 ± 3.3
All Grps (N = 72) 74.1 ± 89.7 10.5 ± 3.1 6.8 ± 2.6
1. Overall group difference using one-way ANOVA [F(4;67) = 4.24; p = 0.004]. 2. Overall group difference using one-way ANOVA [F(4;66) = 15.13; p <
0.0001]. 3. Overall group difference for weight using one-way ANOVA [F(4;67) = 11.28; p < 0.0001]. * one subject is missing for age for ECS study.
0.01 for all comparisons). None of the other groups re-
vealed significant comparisons between-groups. This
again was controlled for by using “study” as a control
variable.
Moreover, a significant weight effect was observed.
On Newman-Keuls post-hoc testing, significant differ-
ences (p < 0.05) are noted between all study groups ex-
cept between the “fluoxetine” and “ziprasidone” studies
and between the “ECS” and “VFD2” study. Thus,
“weight” was used as a covariate.
For sex distribution, 33 subjects were male whereas 37
were female. No difference in sex distribution was noted,
but because of potential sex differences, sex was used as
a factor or covariate, depending on the analysis.
Figure 1. Scatterplot of Neurogenesis Rates of Old World
Monkeys as Reflected by Rates of Doublecortin counts in
the dentate gyrus of the hippocampus ver sus age in months.
3.1. Continuous Measures
For univariate Pearson’s correlations, weight did not
correlate significantly with neurogenesis rates as re-
flected by doublecortin (r = −0.10; N = 72; p = 0.39)
whereas age did correlate significantly with neurogenesis
rates (r = −0.47; N = 71; p < 0.001) (see Figure 1).
Given the non-linear relationship between age and neu-
rogenesis rates, we examined this relationship using uni-
variate non-linear regression analysis, which revealed a
numerically more robust relationship [F (1;69) = 19.88; p
= 0.00003] in comparison to the linear model (see Figure
1).
Table 3. Prediction of doublecortin staining within the den-
tate gyrus of the hippocampus by age and other control
variables.
Parameter DF F p
Weight 1 1.09 0.30
Age 1 18.84 0.00005
Study 1 0.52 0.47
Experimental Control1 0.39 0.53
Error 66
The first general linear model used doublecortin as the
dependent variable, and entered study and experimental
status (control versus non-control) as categorical vari-
ables, and age and weight as continuous predictor vari-
ables. Age predicted doublecortin expression (see Table
3), independent of all the aforementioned variables. As
mentioned, sex is confounded with study, so sex had to
be included into an additional analysis. There is a trend
for study effect which in all likelihood represented lower
doublecortin expression in the ziprasidone study.
fect was still evident when controlling for sex (Table 4 ).
In this second analysis, a trend for a weight effect was
also observed and is consistent with our previous paper
examining correlation between weight and neurogenesis
in the subjects in the “VFD1 study” [21]. A Pearson cor-
relation run only in the control subjects revealed a sig-
nificant inverse relationship between age and neurogene-
sis reflected as doublecortin staining [r = −0.57; N = 18;
p = 0.014]. Therefore, we demonstrate that age signifi-
We then conducted the analysis without study number,
in order to examine for potential sex effects. No sex ef-
fect was observed, although a highly significant age ef-

Relationship between Age and Neurogenesis in Old World Monkeys
176
cantly predicts doublecortin expression, independent of
weight, sex, study type and experimental control status.
3.2. Categorical Measures
When the subjects were split into two age groups with
the median age of <9 years of age as the “younger” group
and 9 years or greater for the “older” group, the younger
group showed significantly more cells expressing dou-
blecortin in comparison to the older group [139.55 ±
122.86 in younger subjects versus 49.43 ± 57.42 (N = 51)
in older subjects; (t-value = 4.22; df = 69; p = 0.00007)]
(Figure 2). Correlation analyses in each group consid-
ered separately reveals no age effect in the younger
group but a significant inverse age effect is observed in
the older age group (r = −0.38; N = 51; p = 0.005). These
data suggest a linear fall off of neurogenesis following
full adulthood but less of an age effect during young
adulthood.
4. Discussion
The results of this study show that with advancing age,
there is a decline in neurogenesis within the subgranular
Figure 2. Mean ± SD of neurogenesis rates of Old World
monkeys as reflected by rates of doublecortin counts in the
dentate gyrus of the hippocampus in subjects split based on
median age.
Table 4. Prediction of doublecortin staining within the den-
tate gyrus of the hippocampus by age wi th study omitted as
control variable.
DF F P
Sex 1 1.10 0.30
Experimental Control 1 0.30 0.58
Weight 1 3.16 0.08
Age 1 10.83 0.0016
Error 66
zone of the hippocampus in adult mammals. Our study is
consistent with the results of earlier smaller studies of
New World Monkeys that show an inverse relationship
between neurogenesis within dentate gyrus and age [8].
However, we found that instead of a linear decline in
neurogenesis throughout the bonnet macaque lifespan,
we observed a non-significant relationship between age
and new hippocampal neurons expressing doublecortin
for subjects less than 9 years old (corresponding to young
and full adulthood). However, there was a linear signifi-
cant decline for subjects 9 years or greater (middle age
and senescence). This suggests that neurogenesis contin-
ues steadily in the Bonnet macaque throughout lifespan
until middle age and then begins to decline through mid-
dle age to senescence. The reason for the difference be-
tween our study and other studies that indicates a linear
decline across the full age range [8] is unclear but may
involve species differences and phylum (Old World ver-
sus New World monkeys) and the former being more
closely related to humans.
The trend of weight effect that was observed when con-
trolling for sex was consistent with our previous paper
examining correlation between weight and neurogenesis
in the subjects in the “VFD1 study” [21]. Statistical
analysis revealed that there was an overlap between the
effect of study and age. This limitation in the results was
partially due to the variation of the mean ages between
each study, and was especially prominent with the sub-
jects of the ziprasidone (Geodon) study. However, we
tried to minimize this effect by controlling for “study” as
one of our covariates. Furthermore, excluding the zipra-
sidone study data from the analysis did not yield a sig-
nificant difference.
Mechanisms of Age Related Decline in
Neurogenesis
Aging induces important changes in neuroendocrinology
and neurochemistry of the brain that involve the synthe-
sis of neurotransmitters, growth factors, neuropeptides
and steroids [22]. Age-related decline in neurogenesis
can be explained by such aforementioned changes in
local and systemic environments that no longer provide
the necessary mitotic stimuli for cell proliferation. Pre-
vious studies show that inducers of neurogenesis de-
crease with age, whereas signals that interfere with neu-
rogenesis increase with age. Indeed, age-related de-
creases in neurogenesis can be prevented by the deacti-
vation of these positive regulators [23-25]. This effect is
thought to occur by an increase in the number of cells
within the dentate gyrus, rather than the deceleration of a
slowed cell cycle. The additional dividing cells could
come from precursors that have become quiescent over
time, i.e., cells that are not dividing but have retained
their capacity to divide [26].

Relationship between Age and Neurogenesis in Old World Monkeys 177
Glucocorticoids have been shown to be among the
most potent negative regulators of neurogenesis. Gluco-
corticoids are released into the blood circulation follow-
ing the activation of the hypothalamo-pituitary-adrenal
(HPA) axis, primarily by stress. Acute [27] or chronic
[28] treatment with corticosterone, the main glucocorti-
coid in rodents, has been shown to be a strong negative
regulator of cell proliferation in the adult dentate gyrus.
Corticosterone-mediated downregulation of cell prolif-
eration in the adult dentate gyrus has also been accom-
plished by exposing mice [29,30] to various paradigms of
stress. Removal of the stress stimulus, however, can
completely reverse the changes in neuronal differentia-
tion in 3 weeks [30]. Furthermore, in adult rodents, adre-
nalectomy stimulates cell proliferation in the dentate
gyrus [31].
Chronically elevated glucocorticoid levels, therefore,
are thought to be responsible, in part, for reduced neuro-
genesis in the aging dentate gyrus. Evidence for this
comes from rodent studies that show elevated basal lev-
els of corticosterone mainly during the dark phase of the
circadian cycle, and prolonged secretion after stress.
Both basal and stress-induced corticosterone secretion is
blocked by an adrenalectomy in mid-adulthood, and is
associated with increased cell proliferation and neuro-
genesis in senescent animals [32]. When adrenalectomy
is performed on senescent rats, there is a decrease in cor-
ticosterone levels and increased cell proliferation in the
dentate gyrus [23,33]. There are also changes in the re-
sponse to corticosterone with age. Aged rats have higher
expression of glucocorticoid receptors in early precursors,
and calretinin-positive immature neurons, which are de-
void of glucocorticoid receptors or mineralocorticoid
receptor expression in younger mice, come to acquire
both receptors in old age [34]. Thus, corticosteroid medi-
ated decline in neurogenesis in older ages may operate
via increased basal levels, as well as increased sensitivity
to hormone action.
Numerous neurotransmitters have also been shown to
modulate neurogenesis. Glutamate is a negative regulator
of neurogenesis [35,36]. NMDA receptor antagonism can
reverse the decline of neurogenesis in the aged brain [37].
Furthermore, it was shown that the effects of corticos-
terone on cell division could be blocked by treatments
that activate or inactivate NMDA receptors suggesting
that glutamate works via a common pathway with corti-
costeroids [38]. GABA was also shown to be a negative
regulator of neurogenesis. In aged animals, infusion of
Preg-S, a negative allosteric regulator of GABA binding,
considerably increases the rate of cell proliferation and
neurogenesis [39]. GABAergic neurotransmission, more-
over, becomes elevated with age [40]. Taken together,
this evidence suggests that decreases in GABA may po-
tentially contribute to age-related decline in neurogene-
sis.
Lastly, serotonin has been shown to modulate neuro-
genesis, mainly through the action of the presynaptic and
postsynaptic 5HT1a [41]. Studies that show decreased
serotonin levels, as well as 5HT1a binding declines with
ageing, supporting the idea that decreased serotonergic
activity also contributes to the decline in neurogenesis
with age. In addition to hormones and neurotransmitters,
numerous neurotrophic factors including EGF, IGF-1,
VEGF, FGF-2, and BDNF have been shown to decrease
in middle age and have been associated with decreased
cell proliferation in the dentate gyrus and the subven-
tricular zone [42-45].
The studies conducted thus far suggest that multiple
neuropeptides and other mediators exert a deleterious
effect on neurogenesis in the hippocampus. However, it
is also possible that with age, changes occur to the pre-
cursor cells themselves, such that they no longer can re-
spond to the normal growth stimuli. While current data
do suggest that the main change in precursor cells that
occurs with age is their decrease in rate of proliferation,
the mechanisms responsible for this effect are unclear.
Recent studies using stem cell marker SOX-2 to differen-
tiate stem cells from Brdu-labeled proliferating cells
show that the overall number of Sox-2 labeled cells re-
mains constant throughout the lifespan while the number
of cells expressing endogenous proliferation marker de-
clines significantly with age [44,46]. The results of this
study suggest that the decline in neurogenesis rates is due
to the increased quiescence of active precursor cells,
rather than the progressive loss of the total number of
precursors. A further comparison of the Sox-2/BrdU data
with Sox-2/Ki67 in this study suggests that there is a
lengthening in cell cycle that occurs with age. Thus, with
age, both the increased quiescence, as well as lengthen-
ing of the cell cycle may contribute to the decline in the
rate of neurogenesis.
5. Acknowledgements
We wish to thank Drs Christopher Lange and David Lee
for their invaluable contributions
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