This document summarizes research on ageless plants and animals that display negligible senescence. It discusses various theories of aging, including mutation accumulation, antagonistic pleiotropy, and programmed cell death. Examples of animals that may age slowly or not at all include yellow rockfish, tortoises, jellyfish, bowhead whales, and lobsters. Plants discussed include ancient bristlecone pines, aspen clones, and olive trees over thousands of years old. Factors like telomere length, antioxidants, and metabolism are hypothesized to influence longevity. Strategies for engineered negligible senescence in humans are also briefly outlined.

1. Ageless Animals and Plants
Richa Banthia
BIOL 4097
September 9th, 2014

2. Introduction & Outline
• Ageless Plants and Animals – Where is this
research heading? Is aging not a requirement?
• What is Aging?
– Mechanisms of Aging
– Theories of Aging
• What is Negligible Senescence?
• Review of Plants & Animals displaying NS
• Conclusion and modern day Research

3. Survivorship vs. Age
http://poseidonsciences.scienceblog.com/files/2010/08/Aging-Scienceblog-Survivorship-curve-2006-Census.jpg

4. Average Life Span in the US
• Current Life Expectancy
78.74 years
http://i.dailymail.co.uk/i/pix/2013/01/09/article-2259763-16D65AD6000005DC-767_306x423.jpg

5. Supercentenarians
• Jeanne Calment (1875-1997)
• Longest living person at 122 years old
• Met Vincent van Goh, ate 2 lbs. of chocolate EVERY
week, rubbed her skin with olive oil
http://www.nytimes.com/1997/08/05/world/jeanne-calment-world-s-elder-dies-at-122.html

6. Supercentenarians: 127 year old
Leandra Lumbreras
http://metrouk2.files.wordpress.com/2014/08/166.png

7. Supercentenarians
• Mexican woman Leandra Becerra
Lumbreras turned 127 years old on Sunday,
August 31st.
• Born: August 31st, 1887 (no birth certificate)
• 73 great-grand children
• 55 great-great grand children
• Secrets to long life: sing, eat chocolate,
sleep and don’t get married
http://www.dailymail.co.uk/news/article-2739036/Mexican-woman-Leandra-Becerra-Lumbreras-oldest-
person-lived-127.html

8. What is aging?
• Defined as “the condition or process of
deterioration with age” and “the loss of a
cell’s power of division and growth.”
• Involves deterioration of cardiovascular,
digestive, nervous, reproductive and urinary
systems.
• More prone to development of age related
diseases
http://www.hindawi.com/journals/tswj/2002/704240/abs/

9. Challenges of Aging
Age Related Diseases
• Arthritis
• Cancer
• Alzheimer’s
• Diabetes
• Heart Disease
• Depression
Age Related Conditions
• Loss of hearing, vision,
etc.
• Loss of coordination
• Increased proportion of
fat to muscle
• Loss of bone density

10. Three Classical Theories of Aging
1. Mutation Accumulation Theory
Sir Peter Medawar 1952
• Suggests that random mutations accumulate
later in life such that they cannot be selected
against
• Why? By this time, you will have already
passed your genes to offspring.
• Over time, these mutations accumulate
leading to increased mortality in later life.
http://www.hindawi.com/journals/tswj/2002/704240/abs/

11. Three Classical Theories of Aging
2. Antagonistic Pleiotropy Theory
George C. Williams 1957
• Pleiotropy: one gene influences multiple
phenotypic traits
• Tradeoff between fertility and longevity
• Genes that are beneficial early in life in order
to reproduce, become harmful later in life
• Suggests that if the benefits outweigh the
negatives, the gene will always be selected for.
http://www.hindawi.com/journals/tswj/2002/704240/abs/

12. 2. Antagonistic Pleiotropy Theory
George C. Williams 1957
Example: Testosterone production in males
In early life, production of testosterone controls sex
drive, sperm production, muscle mass, etc. Later in
life, this same action can cause prostate issues.
http://awarnach.mathstat.dal.ca/~joeb/biol3046/projects/AGE2/Antagonistic%20Pleiotropy%20Theory.ht
m

13. Three Classical Theories of Aging
3. Programmed Death Theory
August Weismann 1882
• Aging of cells is genetically programmed
• Supported by the idea that within species, life
span is fairly constant
• Suggested that life span of species is dependent
on the number of somatic cell regenerations
• Other evidence: “senescent cells are resistant to
apoptosis” by inhibiting caspase 3 (part of
programmed cell death pathway) which causes
dysfunction of various tissues
http://www.discoverymedicine.com/Jie-Shen/2009/11/24/programmed-cell-death-and-apoptosis-in-aging-and-life-span-regulation/

14. Programmed Cell Death Pathway
http://www.bumc.bu.edu/phys-biophys/files/2010/04/intrinsic-apoptotic-pathway.
jpg

15. Hayflick’s Limit: Molecular Clock
Leonard Hayflick 1961
• A cell can multiply a limited number of times
• 3 phases of cell growth:
– Phase 1: Rapid cell division
– Phase 2: Cell division slows
– Phase 3: Cells stop dividing : “senescence” and cell
death occurs.
• Human cell’s stop dividing after 50 divisions
http://longevity-science.org/Evolution.htm

16. Hayflick’s Limit
http://www.nature.com/nrm/journal/v1/n1/fig_tab/nrm1000_072a_F3.html

17. Mechanisms of Aging
http://cubocube.com/files/images/e/2/e2ebd42c8333191ad90b0db81f44957566f1961b.jpg

18. Closer Look: Telomere Shortening
• Telomere length and telomere capping both
contribute to cellular senescence
• DNA Polymerase cannot fully
synthesize 3’ end of lagging
strand: End Replication
Problem
• Telomerase synthesizes short
repeating sequence TTAGGG
added to 3’ end of DNA
lagging strand
• Telomere shortening could act
as a cellular time keeper
http://www.senescence.info/telomeres_telomerase.html

19. Telomerase length vs. Age
http://www.nature.com/nrg/journal/v13/n10/images/nrg3246-
f2.jpg

20. Closer Look: Telomere Capping
• Structure via electron
microscopy
• Telomeres form T-loops
that contains TRF-1 and
TRF-2 (Telomere repeat
binding factor)
• Loops prevent telomeres
from being identified as
damaged DNA.
• Also provide stability.
http://www.senescence.info/telomeres_telomerase.html
http://web.pdx.edu/~newmanl/TelomereLoop.gif

21. TRF Length (Capping) vs. Age
http://www.anti-agingfirewalls.com/2014/02/03/nuclear-aging-the-view-from-the-telomere-
end-of-the-chromsome-part-1-context-history-and-about-telomere-lengths-2/

22. Fin? Noggin’? DUUUUDE!
• https://www.youtube.com/watch?v=9YkxZvdCvYM

23. What is negligible senescence?
• What is it? And what does it mean?
According to John C. Guerin…Director
of the Centenarian Rockfish Project at
Oregon State University
• “not only long lived, but they
don’t grow old”
• “Chronological aging without
increased mortality”
• “Continue to grow and reproduce
after reaching maturity but show
no evidence of senescence. In fact
fecundity often increases with
increasing age.”
http://www.lef.org/magazine/mag99/june99-report4.htm

24. Research and Measurement
Techniques
• Determining the age of
animals:
• Whales
– Harpoon points
– Otolith growth rings
– Otolith: structure in
inner ear
• Fish
– Otolith growth rings
http://www.nmfs.noaa.gov/gallery/images/images/photos/20110404_55893
34674.jpg

25. Research and Measurement
Techniques
• Turtles
– Mark and recapture
methods
• Lobster
– Estimation of body size
• Mollusks
– Growth rings in shell

26. ANIMALS DISPLAYING
NEGLIGIBLE SENESCENCE

27. Yellow Rockfish
• Known to live up to 205
years old.
• 2013 Fishing
controversy!
• Found from San Diego
to the Bering Sea
• 16% sold are over the
age of 50

28. Yellow Rockfish
• Hypothesis: Don’t age due to
telomerase expression that
doesn’t decrease with age
• Age measured by examining
the otolith, a structure in the
inner ear.
• Study by Dr. Guido Krupp
shows that telomerase levels
are independent of age.
http://www.agelessanimals.org/research2.htm

29. Aldabra, the giant tortoise
• Aldabra, the giant Tortoise
• Calculated life span of 255
years
• Died early in a zoo in India
due to liver failure and
infection – NOT AGE.
http://io9.com/5618046/the-mystery-of-why-turtles-never-grow-old---and-how-we-can-learn-from-it
http://www.sciencephoto.com/image/378918/350wm/Z7520265-Aldabra_Giant_Tortoise-SPL.jpg

30. Aldabra, the giant tortoise
• Hypothesis: Don’t age due to reactive oxygen
species/ oocyte regeneration/ high telomerase
expression
• ROS: “chemically active free radicals” that are
formed by metabolic energy production. Animals
with slower metabolism have better control of
ROS, thus less likely to have DNA damage.
http://90ways.com/sciarchive/sci61.php

31. Antarctic giant Sponge
• Antarctic sponge estimated to be 10, 000 years old
• Average water temper of 4˚ Celsius slows biochemical
processes
• “Slow motion” living
• Lower rates of respiration, reproduction and
metabolism
http://www.montereyinstitute.org/noaa/lesson06/l6text.htm

32. Jellyfish
• Turritopsis dohrnii
• Benjamin Button jellyfish
• Found in Mediterranean
sea and waters near Japan
• “Immortal” in the sense
that it reverts back to
embryonic form under
stress…keeps rewinding life
cycle.
http://www.ibtimes.com/immortal-jellyfish-ageless-aspen-trees-animals-plants-who-found-fountain-
youth-998646

33. How does it work?
• Jellyfish forms cyst
• Develops into polyp colony
• Jellyfish cells are often totally transformed in
this process. https://www.fightaging.org/archives/2011/04/ageless-animals-the-jellyfish-
edition.php

34. Bowhead Whales
- Discovered to be up to 210 years old
- Age is estimated by investigating the types of
harpoon found in the whale blubber
http://img-fotki.
yandex.ru/get/6713/207833497.1/0_ab022_6b3333a5_XL.jpg

35. Lobsters
• Age is difficult to
measure due to molting
• Only way to estimate
age is based on size
observation
• Some over 3 feet long
• Longevity could be due
to telomerase activity
http://www.smithsonianmag.com/science-nature/dont-listen-to-the-buzz-lobsters-arent-actually-immortal-
88450872/?no-ist

36. Leach’s Storm Petrel
• Small seabird
• Average Life Span: 20
years
• Maximum recorded
lifespan of 36 years.
• How? Telomere length
increases with age.
http://www.bucknell.edu/x45446.xml

37. Leach’s Storm Petrel
Elongation hypothesis: Long lived birds tend to have increasing
length of telomeres
Selection hypothesis: Long lived birds start off with the longest
telomeres http://mbe.oxfordjournals.org/content/25/
1/220.full.pdf+html

38. Naked mole rat
• Only mammal to show
negligible senescence
• Live to 28 years old
• Most rodents of similar
size only live 1-3 years

39. Quahog Clam
• Artica islandica
• Can live up to 400 years
• Found off the coast of
Iceland
• Suggested that
maintained antioxidant
activity increases life
span
http://news.nationalgeographic.com/news/2007/10/071029-oldest-clam.html

40. PLANTS DISPLAYING
NEGLIGIBLE SENESCENCE

41. World’s Oldest Tree: Old Djikko in
Dalarna Province, Sweden
• Spruce tree estimated
to be 9,500 years old
• Dating back to last ice
age using C-14 dating
• Current tree is a clone

42. Pando – The Trembling Giant
• Clonal colony of aspen
trees made up of
50,000 clones
• Located in Utah
• 80, 000 year old root
system
• Common root system
spans 110 acres
http://www.leaflimb.com/blog/wp-content/uploads/2010/04/Pando1.jpg

43. The Senator
• Bald cypress in
Seminole County, FL
• Tardium distichum
• Was the oldest known
Cyprus tree at 3500
years old
• Burned down in 2012
https://www.gunandgame.com/attachments/gen-sherman-jpg.
46821/

44. Methuselah
• Oldest non-clonal tree
estimated to be 4,841
years old
• Bristlecone pine
• White Mountains,
California
• Precise location is a
secret to prevent
damage
http://www.mnn.com/sites/default/files/styles/featured_blog/pub
lic/METHUSELAH.jpg

45. Chestnut Tree of One Hundred Horses
• Chestnut tree on Mount Etna in Sicily – 5 miles from an
active volcano.
• Estimated to be between 2,000 – 4,000 years old
• Circumference of 190 feet – “greatest tree girth” according
to Guinness World Records
• Name comes from a legend where a queen and her 100
knights were able to take shelter under this tree during a
storm.
https://yy2.staticflickr.com/3291/2817869138_30eb23d70d.j
pg

46. Mediterranean Sea Grass
• Posidonia oceanica
• Grass like plants that is
found at the bottom of
the ocean
• Found near Ibiza, Spain
• Spans 5 miles
• Estimated to be
100,000 years old –
world’s oldest organism
http://science.time.com/2014/02/25/worlds-oldest-things/
photo/08_sussman_seagrass_0910_0753_1068px/

47. Olive Tree of Vouves
• Found in the island of
Crete in the Greek isles
• Age: 3200 years
• Continues to produce
high quantity of olives
• Resistant to stressors
such as insects,
droughts, fire, etc.

48. Strategies for Engineered Negligible
Senescence (SENS)
• Dr. Aubrey de Grey
• CEO of SENS
• “master plan to cure aging” by
proposing engineering solutions to
the 7 types of cell damage
• SENS is an extremely controversial
topic
• Goal directed organization to
prevent aging by bringing together
scientists from various fields –
gerontology and engineering.
• Results to completely defeat aging
are still far off in the foreseeable
future
http://mavericksofthemind.com/dr-aubrey-de-grey/6

49. SENS
http://www.sens.org/research/introduction-to-sens-research

50. Conclusion
• Aging is not a requirement and there are many
organisms that display negligible senescence
• Many hypotheses involving telomere length –
continued focus in research.
• Still a controversial topic to apply goals of
negligible senescence to humans
• So for now….eat as much chocolate as possible!
• Questions?

51. References
http://www.smart-publications.com/interviews/mavericks-of-medicine/john-guerin
http://genetics.thetech.org/original_news/news10
http://www.agelessanimals.org/
http://www.hindawi.com/journals/tswj/2002/704240/abs/
http://awarnach.mathstat.dal.ca/~joeb/biol3046/projects/AGE2/Antagonistic%20Pleiotropy%20Theory.htm
http://www.programmed-aging.org/theories/antagonistic_pleiotropy.html
http://poseidonsciences.scienceblog.com/files/2010/08/Aging-Scienceblog-Survivorship-curve-2006-Census.jpg
http://books.google.com/books?id=X5Po92PzOtAC&pg=PA79&lpg=PA79&dq=depletion+of+follicle+and+antagonistic+pleiot
ropy&source=bl&ots=Nh_xGTzbDz&sig=VrQcJUMAcI0EDKkYstp1bCwNG5M&hl=en&sa=X&ei=K_oIVOadB4PgiwK414CgDQ&
ved=0CC8Q6AEwAg#v=onepage&q=depletion%20of%20follicle%20and%20antagonistic%20pleiotropy&f=false
http://www.dailymail.co.uk/news/article-2739036/Mexican-woman-Leandra-Becerra-Lumbreras-oldest-person-lived-
127.html
http://www.discoverymedicine.com/Jie-Shen/2009/11/24/programmed-cell-death-and-apoptosis-in-aging-and-life-span-regulation/
http://www.nmfs.noaa.gov/gallery/images/images/photos/20110404_5589334674.jpg
http://www.mnn.com/sites/default/files/styles/featured_blog/public/METHUSELAH.jpg
http://www.smithsonianmag.com/science-nature/dont-listen-to-the-buzz-lobsters-arent-actually-immortal-88450872/?no-ist
https://www.fightaging.org/archives/2011/04/ageless-animals-the-jellyfish-edition.php
http://www.ibtimes.com/immortal-jellyfish-ageless-aspen-trees-animals-plants-who-found-fountain-youth-998646
http://www.mavericksofthemind.com/wp-content/uploads/2011/11/John-Guerin-Photo.jpg
http://www.senescence.info/telomeres_telomerase.html
http://longevity-science.org/Evolution.htm
http://www.sens.org/research/introduction-to-sens-research
http://mavericksofthemind.com/dr-aubrey-de-grey/6
http://science.time.com/2014/02/25/worlds-oldest-things/photo/08_sussman_seagrass_0910_0753_1068px/