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

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Aging is defined as the inevitable progressive deterioration of anatomical physiological function with increasing age

GrowthRepair

Deterioration

What happens during aging?

› 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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CHANGES…….Whole lot of it……..mostly inevitable….?

Dementia Quick Facts

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Dementia Facts

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Alzheimer’s Disease (AD)

• 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 micro-haemorrhage 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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From an Alzheimer’s brain:

Small blood vessels (green)

Amyloid deposits (red)

Cullen et al. 2005

Risk factors for Alzheimer Dementia

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• 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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10 March 2015- Alzheimer’s Breakthrough

https://au.news.yahoo.com/video/watch/26586743/alzheimer-s-breakthrough/

Microhaemorrhage may be caused by the pulse of the heart beat

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• Needed to meet the oxygen demands of the brain

• Achieved by a low-resistance vascular tree

• 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• The heart’s pulse intensifies several-fold with age, causing tiny vessels to rupture and

cause damage

• A slow and progressive process

The pulse

Bleeding from cerebral vessels

Silent microbleedsHaemorrhagic stroke

Vascular dementia

Insidious-onset dementia (AD)

Plaques, tangles, inflammation

Accelerated by:•Head trauma•ApoE alleles•Familial dementia genes•High Blood Pressure (hypertension) atherosclerosis, uncontrolled diabetes, lack of exercise

if the vessels are large

if the vessels are small (capillaries)

Concept: The pulse of the brain

Accelerated by arterial stiffening

Reverse the biological clock?

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Everyone loves feeling young and strong

Tilting the balance

› 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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Self-protection, repair & recovery from stressors

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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

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, anti-anxiolytic 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

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Mitochondrial dysfunction & oxidative stress (Ischaemia)

(implicated in several neurodegenerative diseases)

Neural damage (with abnormal protein accumulation, i.e. Amyloid-beta, Tau tangles

Dementia

Haemorrhage

Further Vascular damage

At the end of the Day…..

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EAT, SLEEP, EXERCISE in moderation

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

Funding Sources•Sir Zelman Cowen Universities Fund•Sydney Medical & Bluesand Foundation PhD Scholarship

Bosch Advanced Microscopy Facility

THANK YOU for listening

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)

Siva’s Twitter: @PvtScientist

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/abs@.nsf/Lookup/by%20Subject/3303.0~2012~Media%20Release~Heart%20disease%20deaths%20still%20falling,%20but%20dementia%20on%20the%20rise%20(Media%20Release)~1

Statistics to ponder from the Australian Bureau of Statistics