Perminder SachdevCo-Director, Centre for Healthy Brain AgeingDirector, Neuropsychiatric Institute, POWHp.sachdev@unsw.edu.au

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, 1997P.Sachdev@unsw.edu.au

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?