Aging: The First Obstacle to Transhumanists 2...Aging: The First Obstacle to Transhumanists João...
Transcript of Aging: The First Obstacle to Transhumanists 2...Aging: The First Obstacle to Transhumanists João...
October 20, 2018
TransVision
Madrid, Spain
Aging: The First Obstacle to
Transhumanists
João Pedro de Magalhães
Integrative Genomics of Ageing Group
Institute of Ageing and Chronic Disease
University of Liverpool, UK
2
TransVision 2001
“The knowledge that every ambition is doomed to
frustration at the hands of a skeleton have never prevented
the majority of human beings from behaving as though
death were no more than an unfounded rumor.”
Aldous Huxley
50% of people die
within 14 years (75%
in 25 year period)
What will kill you
~50% will die of heart disease and cancer
Almost 75% will die of heart and vascular disease,
cancer and neurodegenerative diseases
Ageing is a sexually transmitted terminal disease
0%
20%
40%
60%
80%
100%
0 500 1000 1500 2000 2500 3000 3500
% a
live
Age (yrs)
Species with negligible senescence
Galapagos photo by Matthew Field; other photos in Public Domain
age-1 identified in 1988
Ageing can be manipulated
by genes and interventions
“...it’s possible that we
could change a human
gene and double our life
span.” – Cynthia Kenyon
Ageing process is plastic
Entries in GenAge Mice Flies Worms Yeast Total
Number of genes 136 193 877 909 2,152
Greatest lifespan
increase46% 150% 10-fold 6-fold -
Tacutu et al. Nucleic Acids Res, 2018
With Fraifeld lab (Israel)
Genes modulating longevity
Longevity pathways from GenAge
Fernandes et al. Hum Mol Genet, 2016
Species Pro-longevity Anti-longevity
Mice p53-signaling pathway
and cell cycle
growth hormone and insulin
signaling, IGF-1 receptor
Flies hypoxia response via HIF
activation
PI3 kinase pathway,
oxidative phosphorylation
and IGF pathway
Worms autophagy oxidative phosphorylation,
mTOR signaling pathway
Yeast ribosome
It is possible to manipulate ageing
Ageing is not merely the sum of age-
related diseases
Manipulations of genes, inc. by diet
and drugs, could dramatically
improve human health
McCay et al. 1935. J Nutrit 10:63-75.
Caloric restriction
Reducing calories extends
healthy lifespan and delays
age-related diseases
Okinawans undergo mild CR and have
better health
CR can help identify drug target genes
(e.g., rapamycin which targets TOR)
“You can live to be a hundred if you give up all the things that make you want to live to be a hundred.” ― Woody Allen
de Magalhaes et al. Pharmacol Rev, 2012
CR health paradigm
http://genomics.senescence.info/drugs/
Barardo et al. Aging Cell, 2017
1316 entries from 27 model organisms
418 drugs/compounds
325 publications
Drugs modulating longevity
Big data approaches
Repurposing compounds for life-extension
de Magalhaes et al., Pharmacol Rev, 2012;
Calvert et al., Aging Cell, 2016
Overlap between longevity
signatures and drugs
4/5 drugs tested in worms
extended lifespan (inc. allantoin)
Burgeoning anti-aging biotech sector
de Magalhaes et al., Trends in Biotech, 2017
Consult/advisor:
Five Alarm Bio, Xobaderm,
Ingenet, P3M Clinic, Apollo
Thera, Genescient,
Androcyte, 4D Pharma,
Aviva
Playing devil’s advocate
Few % companies becomes profitable
Only 1/5000 drug candidates obtains
approval
Long validation times in aging
de Magalhaes et al., Trends in Biotech, 2017
Drug longevity effects in animals
Barardo et al. Aging Cell, 2017
From model organisms to humans
de Magalhaes et al., Trends in Biotech, 2017
Human ageing remains a mystery
Poor biological understanding of human ageing
Poor understanding of the genetics of human longevity
de Magalhaes Cell Cycle, 2014; Trends in Biotech, 2017
• Ageing remains a mystery of biology
– Why do we age?
• Genes (>2000) and drugs (>400) can extend longevity
in animals
– Will they extend human longevity? And by how much?
• Big data to prioritize drugs and targets
– How can we predict clinical outcomes?
• Growth in anti-ageing biotech
– Which intervention will work?
Summary & questions
http://pcwww.liv.ac.uk/~aging/
Lab members:
Daniel Thornton,
Dominic Bennett,
Jacob Edogbanya,
Daniel Palmer, Kasit
Chatsirisupachai,
Saara Marttila,
Daniela Martinez,
Gulam Altab,
Priyanka Raina,
Roberto Avelar
Funding sources: