Transcript Aging talk 2 - WordPress.com

Age-related changes in the brain: An
insight to positive aging
Sivaraman (Siva) Purushothuman
Save Sight Institute at Sydney Eye Hospital;
Bosch Institute at University of Sydney
Aging
Growth
Repair
Deterioration
Aging is defined as the inevitable progressive deterioration of anatomical
physiological function with increasing age
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What happens during aging?
CHANGES…….Whole lot of it……..mostly inevitable….?
› Changes in Physiology
- Cellular
- Tissue/Physical
- Function
› Changes in Health
- Overall fitness
- Disability
- Disease and chronic illness
- Cognition
- Dementia and other brain disorders
› Changes in Lifestyle
- Activities
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Dementia Quick Facts
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Dementia Facts
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Alzheimer’s Disease (AD)
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Alzheimer’s disease (AD) is the most common type of dementia
Debilitating, progressive and no known cure is available
90% occur sporadically, and is age-related (usually >65 years)
At the neuropathological level of AD, many authors still consider amyloid
plaques and neurofibrillary tangles to be ‘hallmark’ lesions
- In AD, plaques first develop in areas of the brain used for memory and other
cognitive functions- the temporal and parietal lobes of the brain
• Amyloid plaques form exactly where capillaries bleed – i.e. that microhaemorrhage causes plaque formation
- High impact sportsmen and traumatic brain injury victims (including war veterans)
have a high incidence of early onset of Alzheimer-like dementia (dementia
pugilistica or chronic traumatic encephalopathy)
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Cullen et al. 2005
From an Alzheimer’s brain:
Small blood vessels (green)
Amyloid deposits (red)
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Risk factors for Alzheimer Dementia
• Major risk factors are age, family history, traumatic brain
injury or stress, and cardiovascular disease
• Several cardiovascular disease (modifiable or lifestyle) risk
factors overlap with AD
• Obesity, high cholesterol, and hypertension in midlife, atherosclerosis,
smoking, diabetes and sedentary lifestyle
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Microhaemorrhage may be caused by the
pulse of the heart beat
10 March 2015- Alzheimer’s Breakthrough
https://au.news.yahoo.com/video/watch/26586743/alzheimer-s-breakthrough/
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The pulse of the heart beat may lead to
dementia
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20% of the blood output from each heartbeat supplies the brain directly
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Needed to meet the oxygen demands of the brain
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Achieved by a low-resistance vascular tree
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Enables the pulse to penetrate the deeper capillary bed of the brain
So, the brain ‘feels’ every pulse of the heartbeat
In our youth, our blood vessels are elastic and flexible
Blood vessels are more prone to stiffening with age
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The heart’s pulse intensifies several-fold with age, causing tiny vessels to rupture and
cause damage
A slow and progressive process
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Concept: The pulse of the brain
The pulse
Accelerated by:
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Accelerated by
arterial stiffening
Bleeding from cerebral
vessels
if the vessels
are large
Haemorrhagic stroke
Head trauma
ApoE alleles
Familial dementia genes
High Blood Pressure
(hypertension) atherosclerosis,
uncontrolled diabetes, lack of
exercise
if the vessels are small
(capillaries)
Silent microbleeds
Plaques, tangles, inflammation
Vascular dementia
Insidious-onset dementia
(AD)
Reverse the biological clock?
Everyone loves feeling young and strong
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Tilting the balance
Self-protection, repair & recovery from stressors
› Preconditioning (adaptation)- exposing to lower level stress/stimulus in
order to prepare for a later encounter with a similar, larger dose stressor
- Vaccination
- Ischaemic or hypoxic (reduced oxygen) stress- against cerebral ischaemia and
cardiac infarction. It is even used to condition for high level sports performance.
- Physical Exercise
- Certain Diet? e.g. fasting, caloric restriction?
› The mechanisms for preconditioning (mainly) point towards the
Mitochondria within cells
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› Mitochondria are the major energy producing organelles in living cells
› By-products of ATP production are harmful free radicals
› Damaged cells reduce ATP but increase the production of free radicals (oxidative stress)
› Accumulated damage is detrimental to cells and tissue- Mitochondrial damage and
oxidative stress is implicated in several neurodegenerative conditions like Alzheimer’s &
Parkinson’s Diseases
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Infrared light therapy
› Also known as Low-intensity light therapy (LLLT) or Photobiomodulation :
Wavelength 600- 1,000nm. We used near infrared light
› Initially developed by NASA to harness infrared energy to grow plants in outer
space
› Shown to accelerate wound healing in a range of soft tissue injuries (e.g. sports
and battle injuries).
› Shown to be neuroprotective. Current human clinical trials for stroke and retinal
diseases
› Infrared light is believed to be absorbed by the mitochondria, to repair damaged
forms of the enzyme, and to restore
mitochondrial function and reduce free radicals
› Infrared also upregulate and initiate the production
of key growth factors and other repair proteins
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Dietary Saffron
› Saffron (crocus sativus) is a well-known spice, used widely in various
cuisines
› Traditionally used as medicine for various ailments: Evidence from India,
Egypt, Rome, Greece, Persia
› Epidemiological studies show low incidence of dementia in certain regions
› Saffron has strong anti-oxidant, anti-carcinogenic, anti-depressant, antianxiolytic and anti-inflammatory properties
› Has the most total anti-oxidant capacity when compared to various food
compounds (nuts, herbs, spices, sweets, fruits, cereals)
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What we found from our work…
› Dietary saffron and infrared light may provide protection throughout the
central nervous system. The mechanism of its action remains to be
defined, but may involve the regulation of several protective pathways.
› Our work indicates that saffron and infrared light offer neuroprotection:
Reduction of oxidative stress, pathological markers (Amyloid-beta & Tau
tangles in Alzheimer’s disease) and enhances mitochondrial and cellular
function.
› Saffron and infrared light are examples of effective, non-invasive, easy to
administer therapeutic interventions for neurodegenerative conditions.
› These therapies give hope for protection, preservation and rescue of
surviving but stressed neurones, a goal not achieved by current treatments
for neurodegenerative diseases.
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So….therefore
Haemorrhage
Further Vascular damage
Mitochondrial dysfunction & oxidative stress (Ischaemia)
(implicated in several neurodegenerative diseases)
Neural damage (with abnormal protein
accumulation, i.e. Amyloid-beta, Tau tangles
Dementia
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At the end of the Day…..
EAT, SLEEP, EXERCISE in moderation
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Cerebral & Retinal Neurobiology Lab
(Physiology Dept & Bosch Institute)
• Prof. Jonathan Stone
• Prof. John Mitrofanis
• Dr. Daniel Johnstone
• Charith Nandasena
• Sharon Spana
• Alice Brandli
• Charean Adams
Brain & Mind Institute (Uni Sydney)
• Prof. Lars Ittner
• Prof. Jurgen Gotz
• Dr. Janet Van Eersel
Current & Previous collaborators
•Dr. Karen Cullen (Uni Sydney)
•Prof Michael O’Rourke (Victor Chang
Institute)
•Prof Eli Keshet (University of
Jerusalem)
Bosch Advanced Microscopy Facility
Funding Sources
• Sir Zelman Cowen Universities Fund
• Sydney Medical & Bluesand
Foundation PhD Scholarship
Siva’s Twitter: @PvtScientist
THANK YOU
for listening
Statistics to ponder from the Australian Bureau of Statistics
Heart disease deaths still falling, but dementia on the rise:
In “Causes of Death” Australian Bureau of Statistics Media Release (25 March 2014)
•Deaths from heart disease have fallen steadily since 2003, while deaths from dementia and Alzheimer’s disease continue to increase,
according to figures released today by the Australian Bureau of Statistics.
•“Heart disease is still the leading cause of death, with 20,046 deaths in 2012, however this has fallen steadily since 2003. Heart disease
accounted for 14 per cent of all deaths in 2012 compared to 19 per cent of all deaths in 2003," said James Eynstone-Hinkins, ABS
Director of the Health and Vitals Statistics Unit.
•“There were 10,779 deaths from Cerebrovascular diseases (including haemorrhages, strokes, infarctions and blocked arteries of the
brain) in 2012, making these the second most common cause of death.
•“Dementia and Alzheimer’s disease was the third leading cause of death, accounting for 10,369 or seven per cent of all deaths in 2012.
Most (95 per cent) of these deaths occurred in people aged 75 or over.
•“For women, dementia and Alzheimer's disease has overtaken Cerebrovascular diseases as the second leading cause of death in 2012,
while breast cancer remained the sixth most common cause of death.
•“For men, lung cancer remains the second leading cause of death. Dementia and Alzheimer's disease is now the fifth leading cause,
replacing prostate cancer which is now ranked sixth for males.
http://www.abs.gov.au/ausstats/[email protected]/Lookup/by%20Subject/3303.0~2012~Media%20Release~Heart%20disease%20deaths%20still
%20falling,%20but%20dementia%20on%20the%20rise%20(Media%20Release)~1