Imortalidade - Em busca de Como Não Morrer - Synbio USP

Imortalidade
A TECNOLOGIA NOS PERMITIRÁ VIVER PARA SEMPRE?

Um desejo Antigo
Edwin Smith Papyrus: “O início do livro
para fazer de um homem velho,
jovem...”
The Book of Immortality: The Science, Belief, and Magic Behind Living Forever Por Adam Gollner
Epopeia de Gilgamesh: “A vida que você
procura nunca encontrará."

Ao longo dos séculos
Luigi Cornaro
1467 - 1566
Francis Bacon
1561 -1626
“Para falar com clareza e simplicidade, esse fim
consiste na descoberta de todas as operações e
possibilidades de operação: desde a imortalidade
(se é possível) até a mais desprezada arte mecânica”
ZATERKA, Luciana. Francis Bacon e a questão da longevidade humana. Sci. stud.[online]. 2015, vol.13, n.3 [cited 2016-05-09], pp.495-517. Available from:
<http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-31662015000300495&lng=en&nrm=iso>. ISSN 2316-8994. http://dx.doi.org/10.1590/S1678-31662015000300002.
“The rapid progress true science now makes,
occasions my regretting sometimes that I was born
too soon. (...) all diseases may by sure means be
prevented or cured, (not excepting even that of old
age,) and our lives lengthened at pleasure, even
beyond the antediluvian standard.”
Benjamin Franklin
1706 -1790

O que é Envelhecimento e Morte?
 Envelhecimento
 Alterações biológicas, psicológicas, cognitivas e sociais que aumentam a predisposição a
situações de incapacidade funcional, multimorbidade e aumento de risco a situações de
vulnerabilidade. (Perracini et al., 2009)
 Envelhecimento biológico, ou senescência, é a deterioração progressiva da quase totalidade
das funções do organismo ao longo do tempo. (Austad, 1997)
 Morte
 “Com a descoberta dos aparelhos de ventilação pulmonar, o conceito de morte evoluiu do
último suspiro para uma hierarquia de valores na qual certas atividades do sistema nervoso
central valem mais do que todas as outras do organismo. São atividades essenciais para
caracterizar a condição humana. Na ausência delas, admitimos extinta a vida, mesmo que os
outros órgãos continuem saudáveis.” (O MOMENTO DA MORTE. Drauzio Varella, 2011)
AUSTAD, Steven N.; Why we age; Nova Iorque; John Wiley & Sons, Inc; 1997.
PERRACINI,Monica Rodrigues et al.Funcionalidade e envelhecimento. Guanabara koogan, Rio de janeiro ,2009.
http://drauziovarella.com.br/drauzio/o-momento-da-morte/

Idade X Morte
Mortality rates, expressed in deaths per 100,000 people, as a function of age for the 2002 US population. The black line represents the Gompertz function extrapolated
from the mortality rates after maturity. Source: CDC/NCHS, National Vital Statistics System, Mortality Data.

Idade X Doeças
Mortality rates, expressed in deaths per 100,000 people, as a function of age for the 2002 US population. The black line represents the Gompertz function extrapolated
from the mortality rates after maturity. Source: CDC/NCHS, National Vital Statistics System, Mortality Data.

Entendendo a Senescência:
Alex e o coraçãozinho de frango
On January 17, 1912
Alex Carrel placed a
slice of heart muscle
from a chick embryo
in a culture medium.
The cells lived until
1946. They stopped
pulsating two years
after Carrel himself
died of a heart attack.

O Limite de Hayflick
Hayflick L, Moorhead PS (1961). "The serial cultivation of human diploid cell strains". Exp Cell Res 25 (3): 585–621. doi:10.1016/0014-4827(61)90192-6. PMID 13905658.

Radicais Livres de Harman
https://en.wikipedia.org/wiki/Denham_Harman

McCay, C. M.; Crowell, Mary F.; Crowell (November 1934). "Prolonging the Life Span". The Scientific Monthly 39 (5): 405–414. Bibcode:1934SciMo..39..405M. JSTOR 15813.
The Scientific Monthly © 1934
Os ratos magros do Dr. McCay

Os vermes mutantes de Klass
Klass MR (1983). "A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results". MECHANISMS OF AGEING AND DEVELOPMENT 22 (3-4): 279–
286. doi:10.1016/0047-6374(83)90082-9. PMID 6632998.
Ayyadevara S, Alla R, Thaden JJ, Shmookler Reis RJ (2008). "Remarkable longevity and stress resistance of nematode PI3K-null mutants". Aging Cell 7(1): 13–22. doi:10.1111/j.1474-
9726.2007.00348.x.PMID 17996009.
Over 1800 genes altering
lifespan in model organisms

Seres vivos (praticamente) imortais
Espécies de HidraSilene acaulis
Pinus aristata
Lagosta americana
Rato-toupeira-pelado
http://www.bbc.com/earth/story/20150622-can-anything-live-forever

Causas de envelhecimento
https://www.futurelearn.com/courses/ageing/

Genetic factors are suggested to account for up to
16–25% of the variation in long-livedness
Genética do envelhecimento

Síndromes progeróides
 Síndrome de Werner
 Causada por mutação no gene WRN que
desenrola o DNA na replicação do DNA.
 Síndrome de Hutchinson-Gilford
 Causado por uma mutação no gene LMNA
(c.C1824T/p.G608G)

Criogenia
• Idealizado inicialmente em 1922 por Alexander
Yaroslavsky
• James Bedford foi o primeiro homem
criopreservado, em 1967 (Bedford Day)
• 250 pessoas criopreservadas nos EUA
(entre corpos inteiros e cabeças)
• 33 animais de estimação
Moen, Ole Martin. "The case for cryonics." Journal of medical ethics 41.8 (2015): 677-681.
https://en.wikipedia.org/wiki/Cryonics

David Sinclair, Vinho e a Indústria Farmacêutica
Howitz, Konrad T., et al. "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan." Nature 425.6954 (2003): 191-196.

David Sinclair, Vinho e a Indústria Farmacêutica

Ativadores da Telomerase
 Bill Andrews

A “invenção” da Telomerase
de Bill Andrews
http://www.google.com/patents/US6261836?hl=pt-BR&dq=6261836

A “invenção” da Telomerase
de Bill Andrews

De Grey, Adelaide e as fundações
AdG: My mother died in May 2011 and I was her only child; the upshot is that I inherited roughly $16.5 million. Of that,
I assigned $13 million to SENS. (http://www.lifeextension.com/magazine/2013/7/Interview-with-Aubrey-de-Grey-
PhD/Page-01)

Ray Kurzweil e a
Singularidade

Ray’s Breakfast
• porridge (150-350 calories for a half cup, depending on
ingredients)
• berries (85 calories for a cup)
• smoked salmon and mackerel (100 calories for a 3-ounce
serving)
• dark chocolate infused with espresso (170 calories for an ounce)
• vanilla soy milk (100 calories for a cup)
• stevia (zero calories)
• green tea (zero calories)
http://www.techinsider.io/ray-kurzweil-futurist-100-pills-live-forever-2015-11
http://www.businessinsider.com/what-ray-kurzweil-eats-to-live-forever-2016-4
Ray’s +100 pills
• Metformina
• Fosfatidilcolina
• Coenzima Q10
• Testosterona

Human Longevity Inc.
April 21, 2016: up to 500,000 DNA samples
from AstraZeneca clinical trials.

http://www.churchofperpetuallife.org/

Restrição calórica em Humanos
http://archinte.jamanetwork.com/article.aspx?articleid=2517920
Conclusion: Compared with the AL group, the CR
group had significantly:
• improved mood,
• reduced tension,
• improved general health
• Improve sexual drive and relationship
• Improved sleep duration at month.

Restrição proteica em Humanos?
http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00062-X

Comida da Vovó Dora
(Dieta do Mediterrâneo)

The project was conducted in five European
countries: France, Italy, the Netherlands, Poland and
the UK and involved 1,296 participants.
http://www.eufic.org/jpage/en/page/PRESS/fftid/a_mediterranean_style_diet_decreases_levels_of_the_inflammatory_marker/

Restrição calórica em Humanos

Rapamicina
 Medicamento imunossupressor
utilizado em transplantes renais
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356109/

Rapamicina
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786175/
Expressed as life expectancy at 600 days (the age of first
exposure to rapamycin), the effect sizes were 28% for
males and 38% for females.

Partiu tomar rapamicina?
 Ibuprofeno
 Everolimus
Mannick, Joan B.; Del Giudice, Giuseppe; Lattanzi, Maria; Valiante, Nicholas M.; Praestgaard, Jens; Huang, Baisong; Lonetto, Michael A.; Maecker, Holden T.; Kovarik, John (2014-12-24). "mTOR inhibition
improves immune function in the elderly". Science Translational Medicine 6 (268): 268ra179. doi:10.1126/scitranslmed.3009892. ISSN 1946-6242. PMID 25540326.
http://physiolgenomics.physiology.org/content/23/3/343
http://www.bizjournals.com/sanfrancisco/blog/biotech/2014/12/ibuprofen-aging-buck-institute-calico-google.html
 Rapamicina
 Fenformina
 Dasatinibe
 Quercetina

Metformina: a pílula grátis da longevidade
 Medicamento antidiabético usado mais prescrito do Brasil
 Sem efeitos colaterais importantes (redução de B12 a longo prazo)
 Distribuído gratuitamente na rede pública
 Alguns estudos já apontavam redução de doenças cardíacas e cânceres

https://clinicaltrials.gov/ct2/show/NCT02432287

https://www.youtube.com/watch?v=pmeVatAKqVY

Mate as células senescentes, antes que
elas te matem

Mate as células senescentes, antes que
elas te matem
http://dx.doi.org/10.1038/nature16932

Nova classe: Senolíticos
 Dasatinibe  Quercetina
http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract

Aumentar seus telômeros
Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing
mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity,
osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly,
telomerase-treated mice did not develop more cancer than their control littermates.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494070/

https://med.stanford.edu/news/all-news/2015/01/telomere-extension-turns-back-aging-clock-in-cultured-cells.html

Liz Parrish, a primeira pessoa a rejuvenescer?
https://www.inverse.com/article/14614-gene-therapy-makes-bioviva-ceo-elizabeth-parrish-younger-blunter-and-resolute

Liz Parrish, a primeira pessoa a rejuvenescer?
In March 2016, the same tests were taken again by SpectraCell revealed that her telomeres had lengthened by
approximately 20 years, from 6.71kb to 7.33kb. This implies that Parrish’s white blood cells (leukocytes) have become
biologically younger. These findings were independently verified by the Brussels-based non-profit HEALES (HEalthy
Life Extension Company), and the Biogerontology Research Foundation, a UK-based charity committed to combating
age-related diseases.
http://bioviva-science.com/2016/04/21/first-gene-therapy-successful-against-human-aging/
https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_name_is_liz_parrish_ceo_of_bioviva_the/?sort=old

Parabiosis e o rato que rejuvenesce
http://science.sciencemag.org/content/344/6184/649.long

Parabiosis e o rato que rejuvenesce

GDF11 e o rato que rejuvenesce
Growth differentiation factor 11 is
closely related to myostatin. Both are
involved in the regulation of
cardiomyocyte proliferation.

Nanotecnologia
e Engenharia de Tecidos
 Reparo nas células
 Prevenção de doenças
cardiovasculares
 Curando o câncer
 Novos tecidos
 Novos órgãos
 Medicina regenerativa
http://www.understandingnano.com/life-extension-nanotechnology.html http://bme240.eng.uci.edu/students/06s/cphuang/conclusion.html

Nanotecnologia
e Engenharia de Tecidos
http://www.theguardian.com/education/2014/oct/04/penis-transplants-anthony-atala-interview

Hábitos “normais”
http://www.heart.org/HEARTORG/Healthy
Living/PhysicalActivity/FitnessBasics/Ameri
can-Heart-Association-
Recommendations-for-Physical-Activity-
in-
Adults_UCM_307976_Article.jsp#.VzERWo
QrLIV
Chetty, Raj, et al. "The
association between
income and life
expectancy in the United
States, 2001-
2014." JAMA 315.16
(2016): 1750-1766.
http://www.health.harvard.edu/mind-and-mood/happiness-may-not-extend-life
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1000316
Happiness may not
extend life, but friends do
150 minutes per week of
moderate exercise
Higher income was associated
with greater longevity

Ricardo di Lazzaro Filho
@RicLazzaro
www.comonaomorrer.com
Como não Morrer

Imortalidade - Em busca de Como Não Morrer - Synbio USP

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