Aubrey de grey why you're helpless now but not for long

Aubrey D.N.J. de Grey, Ph.D.Chief Science Officer, SENS Research Foundation

[email protected]://www.sens.org/

Most infectious diseases have been easily prevented

Sanitation Vaccines Antibiotics Carrier control

Age-related diseases have not. Why not?

reduced light adaptationreduced ethanol metabolismaltered drug pharmacokineticssomatopauseloss of cardiac adaptabilityincontinenceimpaired wound healingidiopathic axonal polyneuropathyautonomic neuropathyarrhythmiachronic obstructive pulmonary disorderbenign prostatic hypertrophymenopauseleukoaraiosisstrokevascular dementiafrontotemporal dementiaimmunosenescenceanosmiacachexiaanorexia of agingsystolic hypertensionageusiaerectile dysfunctionorthostatic hypotensionimpaired adaptive beta-cell proliferationfibroblast collapseanergic T-cell clonescellular senescencevascular calcificationimpaired transdermal absorptionimpaired thermoregulationreduced tactile acuityimpaired vasoconstrictionloss of neuromuscular junctionsdelayed withdrawal reflex

impaired pH maintenancereduced chemical clearancealtered dermal immune cell residence and functionaberrant allergic and irritant reactionsloss of skin elasticityimpaired vitamin D synthesisreduced renal reserverenal cortex atrophygut dysbiosisloss of jejunal villus heightimpaired response to vaccinationimpaired thirstlentigo senilisthinning hairimpaired proprioceptionimpaired balancereduced vital capacityreduced cardiorespiratory enduranceimpaired sweat responseimpaired blood distributionnutrient malabsorptiondiverticular diseasepresbyphagiaincreased refluxalveolar lossneuronal losssenile emphysemadegenerative disc diseasejoint calcificationpineal calcificationaberrant differentiationgait instabilityfrontal demyelinationaxonal atrophyimpaired functional connectivityimpaired working memory

presbycusisosteoporosisosteoarthritisautoimmunitygreying hairpresbyopiacataractglaucomatemporal arteritispolymyalgia rheumaticawrinklingAlzheimer's diseasePick's diseasecorticobasal degenerationprogressive supranuclear palsyParkinson's diseasemultiple system atrophydementia with Lewy bodiessarcopeniaglomerulonephritissenile cardiac amyloidosisatherosclerosisarteriosclerosisage-related macular degenerationcardiomyopathydiastolic heart failurecancersystemic inflammationoxidative stressreduced coronary blood flowloss of cardiac reserveandropausethymic involutionreduced plasma renin activityreduced aldosteronereduced melatonin diurnal rhythm

Aging is the life-long accumulation of damage to the tissues, cells, and molecules of the body that occurs as an intrinsic side-effect of the body’s normal operation.

“Damage” is changes in structure and composition that the body cannot automatically reverse.

The body can tolerate some damage, but too much of it causes disease and disability.

PathologyMetabolism Damagelife-long late life

Diseases Aging

Communicable Congenital Age-related

TuberculosisMalaria

HIV…

Tay-SachsMELAS

Li-Fraumeni...

Alzheimer’sCancer

Atherosclerosis…

FrailtySarcopenia

Immunosenescence…

Diseases Aging

Communicable Congenital Specific General

TuberculosisMalaria

HIV…

Tay-SachsMELAS

Li-Fraumeni...

Alzheimer’sCancer

Atherosclerosis…

FrailtySarcopenia

Immunosenescence…

Pathology

Geriatrics

Metabolism Damagelife-long late life

Pathology

Gerontology Geriatrics

Metabolism Damagelife-long late life

Pathology

Gerontology Geriatrics

Metabolism Damage(life-long) (late life)

- Pre-therapy damage is not removed

- Can only activate pathways that exist

- Longer-lived species have weaker such pathways

Maintenance

Pathology

Gerontology Geriatrics

Metabolism DamageClaim: unlike the others, the maintenance approach can deliver a

big extension of human healthy lifespan quite soon

Damage type

Cell loss, cell atrophy

Division-obsessed cells

Death-resistant cells

Mitochondrial mutations

Intracellular junk

Extracellular junk

Extracellular matrix stiffening

The maintenance approach

Cell therapy, mainly

Telomerase/ALT gene deletion plus periodic stem cell reseeding

Suicide genes, immune stimulation

Allotopic expression of 13 proteins

Transgenic microbial hydrolases

Phagocytosis by immune stimulation

AGE-breaking molecules/enzymes

Existence of any 8th category is looking increasingly unlikely

This is our Research Advisory Board

See their names, their awesome credentials and their hard-hitting endorsement of our approach at:

www.sens.org/about/leadership/research-advisory-board

Bacterial enzyme protects from oxysterols (Biotech Bioeng, 2012)

Antibodies chop up cardiotoxic amyloid (J Biol Chem, 2014)

Nuclear copies rescue mutant mtDNA (Am J Human Gen, 2008)

Telomerase-KO HSCs rescue telomere-driven anaemia (2014)

Much more ongoing in our research centre and funded labs

Endothelial cell

Lipid-engorged lysosome

Foamcell

Mathieu et al., Biotechnol. Bioeng. 2012; 109:2409

In the short term…We must reorganise our medical research to recognise that the treatment of aging is synonymous with preventing age-related disease and disability. Some progressive thinkers at NIH are attempting this, but progress is predictably glacial.

In the medium term…

Success in developing genuinely effective preventative geriatrics will place it at the heart of medical practice, eliminating the underlying causes of age-related disease.

Long term result:- Nobody gets Alzheimer’s

- Nobody gets heart attacks

- Or cancer, osteoporosis, arthritis, diabetes…

- Age-related diseases are eliminated, with dramatic

consequences for healthspan (and lifespan, yes)

Overpopulation?

Inequality of access?

Immortal dictators?

Boredom?

Pensions collapse?

Overpopulation?

Inequality of access?

Immortal dictators?

Boredom?

Pensions collapse?

No age-related ill-health

Elderly contribute wealth

Energy to explore novelty

Flexible career structure

Not a burden on your kids

Available at Amazon and all good book stores.

Paperback is cheaper, and has an extra chapter!

Visit us on the web athttp://www.sens.org/

Read this (semi-technical) book

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Your challenge: learn more, and help!

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