Growth hormone antagonist, cognition, lifespan, telomerase, and oxidative stress

A compound which acts in the opposite way as growth hormone can reverse some of the signs of aging, a research team that includes a Saint Louis University physician has shown. The finding may be counter-intuitive to some older adults who take growth hormone, thinking it will help revitalize them. [...]

The scientists studied the compound MZ-5-156, a “growth hormone-releasing hormone (GHRH) antagonist.” They conducted their research in the SAMP8 mouse model, a strain engineered for studies of the aging process. Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity (the actions of an enzyme which protects DNA material) and life span, while decreasing tumor activity.
MZ-5-156, like many GHRH antagonists, inhibited several human cancers, including prostate, breast, brain and lung cancers. It also had positive effects on learning, and is linked to improvements in short-term memory. The antioxidant actions led to less oxidative stress, reversing cognitive impairment in the aging mouse. (via.)

Brain-Derived Neurotrophic Factor & Serotonin Effects on Aging, Plasticity & More

BDNF and 5-HT: a dynamic duo in
age-related neuronal plasticity and
neurodegenerative disorders

Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are known to regulate synaptic plasticity, neurogenesis and neuronal survival in the adult brain. These two signals co-regulate one another such that 5-HT stimulates the expression of BDNF, and BDNF enhances the growth and survival of 5-HT neurons. Impaired 5-HT and BDNF signaling is central to depression and anxiety disorders, but could
also play important roles in the pathogenesis of several age-related disorders, including insulin resistance syndrome, Alzheimer’s disease and Huntington’s disease.
Enhancement of BDNF signaling may be a key mechanism whereby cognitive stimulation, exercise, dietary restriction and antidepressant drugs preserve brain function during aging. Behavioral and pharmacological manipulations that enhance 5-HT and BDNF signaling
could help promote healthy brain aging. [...]

By promoting neurogenesis,
synaptic plasticity and cell survival, BDNF plays a pivotal
role in the development and plasticity of the brain. During
development of the cerebral cortex and hippocampus,
BDNF induces the differentiation of neural stem cells into
neurons and promotes the survival of newly generated
neurons [1–3]. BDNF signaling at synapses enhances
long-term potentiation (LTP), a process of synaptic
strengthening associated with learning and memory;
the effect of BDNF on LTP is apparently mediated by
cAMP-response-element-binding protein (CREB), which
regulates the expression of genes involved in LTP and
memory formation [4]. Levels of BDNF are increased in
the hippocampus of rats during and after performance
of a spatial learning task (a radial-arm maze), and both
acquisition and maintenance of spatial memory are
impaired when BDNF levels are decreased using antisense
methods [5]. In rats that had previously acquired
spatial memory by extensive training, suppression of
BDNF expression impaired both reference and working
memory [5]. Another study showed that mice lacking one
copy of the BDNF gene exhibit impaired spatial learning
in the Morris water maze [6]. BDNF also plays an important
role in preventing death of neurons during development,
and promotes cell survival during stressful conditions
such as ischemia and trauma in the adult brain [7]. [...]

[A]ctivation of 5-HT1A receptors can impair learning and
memory whereas 5-HT2A and 5-HT2C receptors facilitate
memory formation [10]. [...]

5-HT can
also promote the survival of neurons in the adult brain, as
demonstrated by the abilities of a 5-HT receptor agonist
and SSRI to protect neurons against excitotoxic and
ischemic injury in animal models [12,13]. There are therefore
several commonalities of function in the CNS for
BDNF and 5-HT in terms of their effects on synaptic
plasticity, neurogenesis and cell survival. [...]

Conversely, BDNF
can stimulate the growth and sprouting of 5-HT neuron
axons innervating the cerebral cortex, thereby presumably
increasing the number of 5-HT synapses in this brain
region [14]. (via: pdf.)