Your ability to reconstruct the whole …

NR2Enhancing the plasticity of the brain
Dr. Max Cynader

brain plasticity: after 20 pounds your biomechanics are different yet you still have to walk gracefully

MEMORY: your ability to reconstruct the whole from a degraded fragment



receptor, receptors


Age-Related Memory Loss & RbAp48

A Single Protein May Help Explain Memory Loss In Old Age
by Jon Hamilton
August 29, 2013
If you’re finding it harder to remember where you put the car keys, the culprit could be a brain protein with a name that’s easy to forget: RbAp48.

A shortage of this protein appears to impair our ability to remember things as we age, researchers report in the current issue of Science Translational Medicine. And boosting levels of RbAP48 in aging brains can reverse memory loss, at least in mice, they say.

The protein was studied in an area of the brain that is generally unaffected by Alzheimer’s disease.
The research “reinforces the emerging idea that Alzheimer’s disease and aging are separate entities,” says Scott Small, a neurologist at Columbia University and one of the study’s authors. It also suggests that, eventually, it should be possible to treat memory loss that’s not related to Alzheimer’s.

original article:
Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48
Sci Transl Med 28 August 2013:  5 (200): 200ra115

Cognitive reserve & late-life dementia

Changing perspectives regarding late-life dementia
Majid Fotuhi, Vladimir Hachinski & Peter J. Whitehouse
Nature Reviews Neurology 5, 649-658 (December 2009)

Individuals over 80 years of age represent the most rapidly growing segment of the population, and late-life dementia has become a major public health concern worldwide.
Development of effective preventive and treatment strategies for late-life dementia relies on a deep understanding of all the processes involved. In the centuries since the Greek philosopher Pythagoras described the inevitable loss of higher cognitive functions with advanced age, various theories regarding the potential culprits have dominated the field, ranging from demonic possession, through ‘hardening of blood vessels’, to Alzheimer disease (AD).
Recent studies suggest that atrophy in the cortex and hippocampus—now considered to be the best determinant of cognitive decline with aging—results from a combination of AD pathology, inflammation, Lewy bodies, and vascular lesions.
A specific constellation of genetic and environmental factors (including apolipoprotein E genotype, obesity, diabetes, hypertension, head trauma, systemic illnesses, and obstructive sleep apnea) contributes to late-life brain atrophy and dementia in each individual.
Only a small percentage of people beyond the age of 80 years have ‘pure AD’ or ‘pure vascular dementia’.
These concepts, formulated as the dynamic polygon hypothesis, have major implications for clinical trials, as any given drug might not be ideal for all elderly people with dementia.

You don’t need cognitive stimulation

John Zeisel on ‘hopeful aging’
Jul 7, 2013

Creative means discovery, creative means learning, creative means invention, creative means comprehension.
We’re always in search of understanding.

You can’t learn, be innovative, discover, be creative with banality.
Playing bingo isn’t going to cut it. It’s not interesting enough.
Looking at a Matisse and saying, “What is this painting about?” — that’s interesting enough.

Sudoku, crossword puzzles — mental exercise is not what I’m talking about.
It doesn’t do it. The term that’s used for those is ‘cognitive stimulation.’
You don’t need cognitive stimulation. You have to have meaning in your life. If it’s meaningful, it will stimulate you.

Is there anything else we can do to help our brains age well?
The basic three are sleep, diet and exercise.

The second level of intervention is stress reduction and creative endeavors: the arts, learning. The learning can be anything. It can be based on aptitudes and skills you already have, or you can also learn new skills. All kinds of learning are as essential as stress reduction.

The biggest misconception is that people with dementia can’t learn.
There are four learning systems in the brain.
One is called episodic learning: there’s an event in my life and I remember what happened.
The second is semantic learning, like learning a word out of context.
Then there’s emotional learning, which revolves around relating to others.
Then the final one is procedural learning, which we learn by repetition, by doing something. It’s how you learn to ride a bike or sign your signature.

People with dementia lose some ability with the first two, but they do not lose their abilities for emotional and procedural learning.

To Keep Your Brain Nimble As You Age, Stretch It


How to Live: A Search for Wisdom

Book Distills The Wisdom Of The Over-70 Set
Talk of the Nation. January 01, 2009

Henry Alford interviews people over the age of 70. “How to Live: A Search for Wisdom From Old People”

A clever person solves a problem; a wise person avoids it. That’s Albert Einstein’s definition of wisdom.

Mr. ALFORD: Yeah. The three biggies for me are doubt, reciprocity and nonattachment:

  • Doubt being this idea that, you know, you can say if A happens and B happens, then usually C will happen. However, there’s always a chance that a grand piano will come crashing down on our heads.
    there’s always wiggle room.
  • Nonattachment is this idea that you shouldn’t fixate on things.
  • Reciprocity, of course, is the “do unto others” kind of thinking.

Trust in God but tie your camel.

Mitochondrial allostatic load

Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids
Nature Reviews Endocrinology  10, 303–310 (2014)
Martin Picard, et al.

The link between chronic psychosocial [stress] and metabolic stress and the pathogenesis of disease has been extensively documented.
Nevertheless, the cellular mechanisms by which stressful life experiences and their associated primary neuroendocrine mediators cause biological damage and increase disease risk remain poorly understood.

The allostatic load model of chronic stress focuses on glucocorticoid dysregulation.
In this Perspectives, we expand upon the metabolic aspects of this model—particularly glucose imbalance—and propose that mitochondrial dysfunction constitutes an early, modifiable target of chronic stress and stress-related health behaviours.
Central to this process is mitochondrial regulation of energy metabolism and cellular signalling.
Chronically elevated glucose levels damage both mitochondria and mitochondrial DNA, generating toxic products that can promote systemic inflammation, alter gene expression and hasten cell ageing.
Consequently, the concept of ‘mitochondrial allostatic load’ defines the deleterious structural and functional changes that mitochondria undergo in response to elevated glucose levels and stress-related pathophysiology.

Young mouse blood rejuvenates old brains

Young blood rejuvenates old brains 
Nature Medicine 20, 582–583 (2014)

Villeda et al. show that young blood contains a factor that reverses some aspects of age-related cognitive impairment in mice. Parabiosis in which aged mice are conjoined with aged mice such that their circulatory systems are connected results in no change in synaptic plasticity.
However, parabiois between aged and young mice results in increased expression of proteins involved in synaptic plasticity, and an increased number of dendritic spines and synaptic plasticity in aged mice, as measured by enhanced long-term potentiation in these mice.