Perminder Sachdev - CHEBA sturgeon. Black coral colony. ... dependence imposed by the regulations of...
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Perminder Sachdev Co-Director, Centre for Healthy Brain Ageing Director, Neuropsychiatric Institute, POWH [email protected]
Transcript of Perminder Sachdev - CHEBA sturgeon. Black coral colony. ... dependence imposed by the regulations of...
Perminder SachdevCo-Director, Centre for Healthy Brain AgeingDirector, Neuropsychiatric Institute, [email protected]
TWO CERTAINTIES OF LIFE
A THIRD CERTAINTY
The postponement of mortality The emergence of the extremely old
PROPORTION OF PEOPLE SURVIVING TO A GIVEN AGE (SURVIVAL CURVES)
ARE AGEING AND DEATH INEVITABLE?
A Great Basin Bristlecone Pine forest
HOW OLD CAN ONE GET?
Life cycle of Pacific salmon
Long-lived aquatic animals
White sturgeon
Black coral colonyaround 4,000 years old
>100 years Turritopsis dohrnii
the immortal jellyfish
Aldabra Giant Tortoise Geochelone gigantea
Highest recorded life span of 255 years
Terrestrial animals
Scientific American Sep 2010
An adult salamanderMsx1 to the Rescue
Honey bee castes have different lifespans even though a queen or a worker can be formed
from the same egg
Madame Jeanne Calment of Arles, France, photographed in 1994 at the age of 119. She died in 1997, aged 122, of ‘natural causes’.
“Living independently until the age of 110….. Despite visual and hearing loss, she maintained autonomy in the face of the dependence imposed by the regulations of a nursing home -refusing care and visitors she did not want, smoking in a public place, and insisting on her daily glass of port..”
Ritchie, [email protected]
Levels of organisation
THE CELLULAR BALANCE
Damage accumulation in
yeast ageing
NATURE|Vol 464|25 March 2010
Telomeres and ageing
Senescence
• Cellular senescence – Hayflick Limit 52 (40-60)
• Mouse 14-28
• Tortoise 100
Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965;37:614-36.
ProgeriaHutchinson-Gilford
Syndrome
Accelerated ageing diseasesWerner SyndromeCockayne’s syndromeXeroderma pigmentosa
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In HGPS patients, the cell nucleus has dramatically aberrant morphology (bottom, right) rather than the uniform shape typically found in healthy individuals (top, right)
The nucleus, mitochondria and ageing.
Mediators of aging and factors that counter the processOxidative stress (free radical) theory of ageing
HOW ENERGY IS ALLOCATED IN THE BODY
Ageing has to be understood in the
context of evolution
Centenarian women’s reproductive systems age slowly
According to the ‘disposable soma theory’, organisms must compromise between
energy allocation to growth and reproduction or somatic maintenance and
repair.
• Genes for inflammation - cytokines• Genes for repair – daf2 in the nematode
Genes for longevity
The genetic regulation of ageing and longevity as explained by the disposable soma theory
Systems biology of ageing T. B. L. Kirkwood
Experiments on dietary restriction
and genetic or chemical alteration of nutrient-sensing
pathways
Fontana et al, 2010. Science
Pathways that influence lifespan extension in response to chronic dietary restriction
Sirtuins
Conserved pathways that regulate organismal and brain ageing
NATURE|Vol 464|25 March 2010
The brain as a potential regulator of organismal ageing
A non-monotonic curveA very low dose of a chemical agent
may trigger from an organism the opposite response to a very high dose
Hormesis (from Greek hormæin, meaning “to excite”) is the term for generally-favourable biological responses to low exposures to toxins and other stressors.
Repetitive mild stress exposure has anti-aging effects•Exercise is a paradigm for hormesis in this respect•Others are heat shock, irradiation, pro-oxidants, hypergravity and food restriction•Some natural and synthetic molecules, such as celasterols from medicinal herbs and curcumin from a spice turmeric have also shown to have hormetic beneficial effects - "hormetins“•Psychological Stress as a hormetin
Not only is she likely to live longer than he does, but she will help him
live longer, too
Why Do Women Live Longer?
LIFESTYLE Maintain a healthy weight Maintain a healthy blood pressure Control diabetes Keep cholesterol low Healthy, low calorie diet Exercise regularly Get married (to someone your age, or younger if you are a man) Keep mentally and socially engaged No smoking; moderate alcohol intake Be conscientious and optimistic Reduce exposure to sun Medication: one multi-vitamin pill a day (Ca, aspirin) Screening and early treatment
The future?
• Genetics• Stem cells• Drugs
Signs of aging, reversedSCIENCE VOL 340 14 JUNE 2013
Will your grand children live to be 150?
