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Aging with Meaning
Definition of aging, Life
expectancy/maximum
lifespan, cellular and organismal
aging, Rapamycin, progeria, telomer
es, aging and cancer, elderly driver
ADONIS SFERA,MD
Rembrandt's self-portrait age 63
Eos and Tithonus
Eos locked Tithonus in a bedroom cupboard and threw away the key in disgust
Aging Offers No Evolutionary
Advantage
 From the evolutionary perspective living past the age of
procreation does not make sense.
Is Old Age a Human Achievement
Wrestled From Nature?
 Most Qualities of Old Age Are Uniquely Human:
-Only human beings care and honor the oldest
members of the species.
-Only human beings care for and remember their
dead.
Harry R. Moody; Aging Concepts and Controversies, 6th ed. Pine Forest Press 2010
Human Beings Have an Inborn
Longing for Meaning
 In old age the question of the ultimate
meaning cannot be postponed any
longer.
Facing the Unknown
 Do not cast me off in old age; when my
strength fails do not forsake me
Psalm 71:9
Facing Memory Loss
“Bodily decay is gloomy in prospect, but of all
human contemplations the most abhorrent is
body without mind”
Thomas Jefferson
G.O.M.E.R—Get Out of My ER
GOMERS –Modern Version of
Tithonus
 Gomers are human beings who have lost
what goes into being human beings. They
want to die, and we will not let them.
We’re cruel to the gomers, by saving
them, and they are cruel to us, by fighting
tooth and nail against our trying to save
them. They hurt us, we hurt them.
Samuel Shem ―The House of God‖
Shall we ration medical care of the
elderly?
 The “fair innings” argument
 Medical ethicist Daniel Callahan
writes:
―Is there an obligation to keep the elderly alive as
long as possible, regardless of the cost of doing
so? Perhaps there is a duty to help young people
to become old people, but not to help the old
become still older indefinitely.‖
―The Crowning Glory of Old Age‖.
 Aging is the goal of life - makes us complete
Freed from the youthful intensity of
physical passions and girded with
knowledge and wisdom, the accrued
influence is “the crowning glory of old
age”.
―Of Old Age‖ Cicero
Cicero
Carl Jung: Aging with Meaning
“A human being would certainly not grow to be seventy or eighty
years old if this longevity had no meaning for the species. The
afternoon of human life must also have a significance of its own and
cannot be merely a pitiful appendage of life’s morning.”
Viktor Frankl: Man's Search for
Meaning
 The primary motivational force in man is the striving to find a
meaning.
 When we are no longer able to change our situation - we
are challenged to change ourselves.
Gene Cohen (1944-2009)
 Cohen suggests the development of a “social portfolio”
to enable everyone to cultivate a sense of
meaning, vitality and dignity in later life.
 Changed the image of aging from one of senescence
and senility to a period of creativity.
Marc E. Agronin; “How We Age”A Doctor’s Journey Into the Heart of Growing Old; Da Capo Press 2011
Free to Find Meaning
Harvard Grant Study
 Began in 1938 - follows the health, happiness and fortunes of
268 male Harvard students, and goes on to this day.
 Continues to yield a treasure trove of data about how
people behave, and change in old age including
predictions of strong indicators to a happy life.
Longitudinal Study of Aging Danish
Twins
Genetics account for 25% of the variation in longevity among
twins, and environmental factors for 50%.
With greater longevity (to age 90 or 100), genetic influences become
more important than environmental factors.
The Blue Zones
Blue Zones: four different regions around the
world in which the highest percentage of
centenarians live.
-Sardinia, Italy;
-Okinawa, Japan;
-Loma Linda, California; and the
-Nicoya Peninsula, Costa Rica.
Buettner asserts that centenarians live longer
and better because of the foods they
eat, the social circles they keep, and their
outlook on life.
―Age I must, but I would rather not‖
“Endpoint” John Updike
 Definition of Aging: a series of time
dependent anatomical and physiological
changes that reduce physiological
reserve and functional capacity (Ahmed
and Tollefsbol 2001).
What is Old?
 Young-old adults: 55-75 y/o
 Old-old adults: 75-85 y/o
 Oldest-old adults: 85+ y/o
Life Expectancy vs. Maximum
Lifespan
 Life expectancy – the average number of years an
individual is expected to live.
 Maximum lifespan –the longest a member of each
species can survive.
Life Expectancy - Increasing
 The number of people over 65 is growing rapidly.
 In 1870 there were 1 million people over 65 in the
US
 In 2000 there were 35 million people over 65.
Maximum Lifespan - Unchanged
 Jeanne Calment (1875-1997)
She reportedly
smoked and
drank a glass of
Port up until the
age 117.
How We Age?
 Sophocles, wrote the story of Oedipus when he was 90.
 Oedipus became king because he solved the famous riddle
of the Sphinx :
“What creature walks on four legs in the morning, two legs at
noon, and three legs in the afternoon?”
Erikson - Stage Nine of Psychosocial
Development

Joan Erikson:
-In the ninth stage the old
person confronts all previous
eight stages again, but this
time all stages converge at
the same time.
-The negative pole now takes
the dominant role over the
positive.
For instance, instead of
confronting trust versus
mistrust, in the ninth stage the
elder confronts mistrust versus
trust
Lars Tornstam - Gerotranscendence
-Becoming less self-occupied
-Increased feeling and attachment with
past generations
-Decreased interest in superficial or
unnecessary social interaction
-Taking care of the body without being
obsessed about it
-Decreased interest in material things
-Positive solitude becomes more
Important
-Decrease in right-wrong duality is
accompanied by an increased
broadmindedness & sense of tolerance
-Fear of death disappears and a new
understanding of life & death emerges
- Increased feeling of cosmic communion
and a redefinition of time, space, life and
death.
Gerotranscendence ?
Why We Age?
 Over 300 theories, but there is no unified theory
of aging.
 Organismal and Cellular Aging
Organismal Aging
-As we age there is a steady
decline in physiologic
reserves
-Recovery takes longer
-Reduced ability to
compensate for illness or
physiologic demands
-Illnesses accumulate in
number and severity
-Physiologic decline plus
disease results in excess
morbidity and disability
Homeostasis, Homeostenosis
and Reserve Capacity
-Reduced capacity to maintain homeostasis during stress
-Decompensation under a variety of mild perturbations- homeostenosis.
Richard W. Besdine, Dinfu Wu;Aging of the Human Nervous System: What do We Know”;Geriatrics, Vol 91,May 2008
Brain Vulnerability and Cognitive
Reserve
 Reduced capacity to maintain homeostasis
 Vulnerability of elderly for delirium even with mild illnesses or
adverse effects of drugs.
Cognitive Reserve A Poet’s
View
My history falls away, like sacks of grain from
a careless farmer’s wagon.
I begin to forget everything.
Joseph Skibell ―A Blessing On The Moon‖
Cellular Aging
 In 1961 Dr. Leonard Hayflick published a
classic paper on cellular aging.
 Normal cells could undergo a limited number
of divisions.
 The Hayflick limit specifies that fetal cells can
only divide 40-60 times before their death.
 Telomeres shorten with each division
Telomeres - ticking ―cellular
clocks‖
 Resemble aglets on the ends of shoelaces
 Each time a cell divides, its telomeres
shorten
Telomerase – lengthen telomeres
during early development
Telomerase is a protein
that is found in all
cells, but in normal
cells, it is turned off.
In abnormal cells like
tumors and germ
cells, however, telomer
ase is active it is
capable of producing
new telomeres in aging
cells.
Telomere Shortening and
Increased Telomerase Activity
 Has been observed in many human diseases,
including atherosclerosis, cancer, aging
syndromes, Alzheimer disease and schizophrenia.
Telomere Shortening in Schizophrenia
 Shortened telomere length in chronic schizophrenia may be contributing to the
progressive deterioration in treatment-resistant schizophrenia.
H-T Kao, R M Cawthon, L E DeLisi, H C Bertisch, F Ji, D Gordon, P Li, M M Benedict, W M Greenberg and B Porton; Rapid telomere
erosion in schizophrenia; Molecular Psychiatry (2008) 13, 118–119; doi:10.1038/sj.mp.4002105
Progeria - telomere damage increases
progerin production
 Patients with progeria experience premature aging.
 Accelerated aging begins at around 16 to 18 months of
age, and by the time they are 10, the children look 70-80.
 Patients on average die of stroke or heart disease
complications by the age of 13
Rapamycin and Progeria
 Sirolimus (Rapamycin) is an immunosuppressant
drug used to prevent rejection in organ
transplantation.
 It was recently shown that rapamycin may treat
the accelerated aging condition progeria.
Fountain of Youth
Lucas Cranach the Elder 1546
Is it possible for the cells of our bodies
to become immortal?
 The answer is YES, but there is a catch. We have to get
cancer to do it.
Henrietta Lacks
He-La cells
Aging vs. Cancer
Longevity - the extent to which the cells retain the capacity to
repair damage done to the DNA.
S Dan Zhang, Yufei Liu, and Danica Chen; SIRT-ain relief from age-inducing stress; AGING, Vol 3, No 2 , pp 158-161
SIRT 3 Protects Genomic Stability to Combat
Aging and Cancer
Damage to DNA
activates "gate-keeping"
tumor suppressors like
p53, which protect
against cancer, but can
promote aging.
"Care-taking" tumor
suppressors like SIRT3
protect against DNA
damage, which may
result in protection
against both aging and
cancer.
Katharine Brown, Stephanie Xie, Xiaolei Qiu, Mary Mohrin, Jiyung Shin, Yufei Liu, Dan Zhang, David T. Scadden , and Danica
Chen ;SIRT3 Reverses Aging-Associated Degeneration; Cell Reports, doi:10.1016/j.celrep.2013.01.005
―Can’t see, can’t hear, can’t
walk, but at least I can drive
Why Is Driving an Issue?
 Automobile crashes are the third leading
cause of death and injury in the United States
with 40,000 to 50, 000 people killed in about 2
million accidents per year.
 In 2001-2002 drivers over the age of 75 had a
higher rate of fatal accidents nationwide. This
problem is expected to grow because by
2024, one in four U.S. drivers will be over age
65.
National Older Driver Research and Training Center
Crashes by Driver Age
(Source: Cerrelli, 1998)
The Law
AD was added to the list of the
disorders that may make driving
hazardous
California is one of the six states in the Nation with mandatory reporting
of persons with disorders that may make driving hazardous, including
Alzheimer’s disease.
California Health and Safety
Code Section 103900
 They are specific to physicians and surgeons
per section 103900 of the Health and Safety
Code.
 The physicians who reports a patient
diagnosed with a disorder characterized by
lapses of consciousness, according to the
Health and Safety code 103900, shall not be
civilly or criminally liable to any patient for
making the report.
Liability
Physicians are considered negligent if they do not inform
patients of medications and medical conditions that can
impair driving
1. Physicians may be held liable for civil damages if they clearly
failed to report an impaired driver who causes a MVC.
2. Immunity is granted to the physician if the patient is reported
prior to a MVC.
3. Document all referrals, recommendations, conversations, and
reports (e.g. copy of a driver retirement letter and “do not
drive”
prescription).
Reporting to the local health
authority
2802 AD and related disorders. Means those illnesses that
damage the brain causing
irreversible, progressive, confusion, disorientation, loss of
memory and judgment.
2806 Disorders characterized by lapses of consciousness.
Loss of consciousness or a marked reduction of alertness
or responsiveness to external stimuli, inability to perform
one or more ADLs, the impairment of the sensory motor
functions used to operate a motor vehicle
California Code of Regulations (CCR) title 17 sub-chapter 2.5―
Disorders characterized by lapses of consciousness‖ sections
2800-2812.
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Aging with meaning

  • 1. Aging with Meaning Definition of aging, Life expectancy/maximum lifespan, cellular and organismal aging, Rapamycin, progeria, telomer es, aging and cancer, elderly driver ADONIS SFERA,MD Rembrandt's self-portrait age 63
  • 2. Eos and Tithonus Eos locked Tithonus in a bedroom cupboard and threw away the key in disgust
  • 3. Aging Offers No Evolutionary Advantage  From the evolutionary perspective living past the age of procreation does not make sense.
  • 4. Is Old Age a Human Achievement Wrestled From Nature?  Most Qualities of Old Age Are Uniquely Human: -Only human beings care and honor the oldest members of the species. -Only human beings care for and remember their dead. Harry R. Moody; Aging Concepts and Controversies, 6th ed. Pine Forest Press 2010
  • 5. Human Beings Have an Inborn Longing for Meaning  In old age the question of the ultimate meaning cannot be postponed any longer.
  • 6. Facing the Unknown  Do not cast me off in old age; when my strength fails do not forsake me Psalm 71:9
  • 7. Facing Memory Loss “Bodily decay is gloomy in prospect, but of all human contemplations the most abhorrent is body without mind” Thomas Jefferson
  • 8.
  • 10. GOMERS –Modern Version of Tithonus  Gomers are human beings who have lost what goes into being human beings. They want to die, and we will not let them. We’re cruel to the gomers, by saving them, and they are cruel to us, by fighting tooth and nail against our trying to save them. They hurt us, we hurt them. Samuel Shem ―The House of God‖
  • 11. Shall we ration medical care of the elderly?  The “fair innings” argument  Medical ethicist Daniel Callahan writes: ―Is there an obligation to keep the elderly alive as long as possible, regardless of the cost of doing so? Perhaps there is a duty to help young people to become old people, but not to help the old become still older indefinitely.‖
  • 12.
  • 13. ―The Crowning Glory of Old Age‖.  Aging is the goal of life - makes us complete Freed from the youthful intensity of physical passions and girded with knowledge and wisdom, the accrued influence is “the crowning glory of old age”. ―Of Old Age‖ Cicero Cicero
  • 14. Carl Jung: Aging with Meaning “A human being would certainly not grow to be seventy or eighty years old if this longevity had no meaning for the species. The afternoon of human life must also have a significance of its own and cannot be merely a pitiful appendage of life’s morning.”
  • 15. Viktor Frankl: Man's Search for Meaning  The primary motivational force in man is the striving to find a meaning.  When we are no longer able to change our situation - we are challenged to change ourselves.
  • 16. Gene Cohen (1944-2009)  Cohen suggests the development of a “social portfolio” to enable everyone to cultivate a sense of meaning, vitality and dignity in later life.  Changed the image of aging from one of senescence and senility to a period of creativity. Marc E. Agronin; “How We Age”A Doctor’s Journey Into the Heart of Growing Old; Da Capo Press 2011
  • 17. Free to Find Meaning
  • 18. Harvard Grant Study  Began in 1938 - follows the health, happiness and fortunes of 268 male Harvard students, and goes on to this day.  Continues to yield a treasure trove of data about how people behave, and change in old age including predictions of strong indicators to a happy life.
  • 19. Longitudinal Study of Aging Danish Twins Genetics account for 25% of the variation in longevity among twins, and environmental factors for 50%. With greater longevity (to age 90 or 100), genetic influences become more important than environmental factors.
  • 20. The Blue Zones Blue Zones: four different regions around the world in which the highest percentage of centenarians live. -Sardinia, Italy; -Okinawa, Japan; -Loma Linda, California; and the -Nicoya Peninsula, Costa Rica. Buettner asserts that centenarians live longer and better because of the foods they eat, the social circles they keep, and their outlook on life.
  • 21. ―Age I must, but I would rather not‖ “Endpoint” John Updike  Definition of Aging: a series of time dependent anatomical and physiological changes that reduce physiological reserve and functional capacity (Ahmed and Tollefsbol 2001).
  • 22. What is Old?  Young-old adults: 55-75 y/o  Old-old adults: 75-85 y/o  Oldest-old adults: 85+ y/o
  • 23. Life Expectancy vs. Maximum Lifespan  Life expectancy – the average number of years an individual is expected to live.  Maximum lifespan –the longest a member of each species can survive.
  • 24. Life Expectancy - Increasing  The number of people over 65 is growing rapidly.  In 1870 there were 1 million people over 65 in the US  In 2000 there were 35 million people over 65.
  • 25. Maximum Lifespan - Unchanged  Jeanne Calment (1875-1997) She reportedly smoked and drank a glass of Port up until the age 117.
  • 26. How We Age?  Sophocles, wrote the story of Oedipus when he was 90.  Oedipus became king because he solved the famous riddle of the Sphinx : “What creature walks on four legs in the morning, two legs at noon, and three legs in the afternoon?”
  • 27. Erikson - Stage Nine of Psychosocial Development  Joan Erikson: -In the ninth stage the old person confronts all previous eight stages again, but this time all stages converge at the same time. -The negative pole now takes the dominant role over the positive. For instance, instead of confronting trust versus mistrust, in the ninth stage the elder confronts mistrust versus trust
  • 28. Lars Tornstam - Gerotranscendence -Becoming less self-occupied -Increased feeling and attachment with past generations -Decreased interest in superficial or unnecessary social interaction -Taking care of the body without being obsessed about it -Decreased interest in material things -Positive solitude becomes more Important -Decrease in right-wrong duality is accompanied by an increased broadmindedness & sense of tolerance -Fear of death disappears and a new understanding of life & death emerges - Increased feeling of cosmic communion and a redefinition of time, space, life and death.
  • 30. Why We Age?  Over 300 theories, but there is no unified theory of aging.  Organismal and Cellular Aging
  • 31. Organismal Aging -As we age there is a steady decline in physiologic reserves -Recovery takes longer -Reduced ability to compensate for illness or physiologic demands -Illnesses accumulate in number and severity -Physiologic decline plus disease results in excess morbidity and disability
  • 32. Homeostasis, Homeostenosis and Reserve Capacity -Reduced capacity to maintain homeostasis during stress -Decompensation under a variety of mild perturbations- homeostenosis. Richard W. Besdine, Dinfu Wu;Aging of the Human Nervous System: What do We Know”;Geriatrics, Vol 91,May 2008
  • 33. Brain Vulnerability and Cognitive Reserve  Reduced capacity to maintain homeostasis  Vulnerability of elderly for delirium even with mild illnesses or adverse effects of drugs.
  • 34. Cognitive Reserve A Poet’s View My history falls away, like sacks of grain from a careless farmer’s wagon. I begin to forget everything. Joseph Skibell ―A Blessing On The Moon‖
  • 35. Cellular Aging  In 1961 Dr. Leonard Hayflick published a classic paper on cellular aging.  Normal cells could undergo a limited number of divisions.  The Hayflick limit specifies that fetal cells can only divide 40-60 times before their death.  Telomeres shorten with each division
  • 36. Telomeres - ticking ―cellular clocks‖  Resemble aglets on the ends of shoelaces  Each time a cell divides, its telomeres shorten
  • 37. Telomerase – lengthen telomeres during early development Telomerase is a protein that is found in all cells, but in normal cells, it is turned off. In abnormal cells like tumors and germ cells, however, telomer ase is active it is capable of producing new telomeres in aging cells.
  • 38. Telomere Shortening and Increased Telomerase Activity  Has been observed in many human diseases, including atherosclerosis, cancer, aging syndromes, Alzheimer disease and schizophrenia.
  • 39. Telomere Shortening in Schizophrenia  Shortened telomere length in chronic schizophrenia may be contributing to the progressive deterioration in treatment-resistant schizophrenia. H-T Kao, R M Cawthon, L E DeLisi, H C Bertisch, F Ji, D Gordon, P Li, M M Benedict, W M Greenberg and B Porton; Rapid telomere erosion in schizophrenia; Molecular Psychiatry (2008) 13, 118–119; doi:10.1038/sj.mp.4002105
  • 40. Progeria - telomere damage increases progerin production  Patients with progeria experience premature aging.  Accelerated aging begins at around 16 to 18 months of age, and by the time they are 10, the children look 70-80.  Patients on average die of stroke or heart disease complications by the age of 13
  • 41. Rapamycin and Progeria  Sirolimus (Rapamycin) is an immunosuppressant drug used to prevent rejection in organ transplantation.  It was recently shown that rapamycin may treat the accelerated aging condition progeria.
  • 42. Fountain of Youth Lucas Cranach the Elder 1546
  • 43. Is it possible for the cells of our bodies to become immortal?  The answer is YES, but there is a catch. We have to get cancer to do it. Henrietta Lacks He-La cells
  • 44. Aging vs. Cancer Longevity - the extent to which the cells retain the capacity to repair damage done to the DNA. S Dan Zhang, Yufei Liu, and Danica Chen; SIRT-ain relief from age-inducing stress; AGING, Vol 3, No 2 , pp 158-161
  • 45. SIRT 3 Protects Genomic Stability to Combat Aging and Cancer Damage to DNA activates "gate-keeping" tumor suppressors like p53, which protect against cancer, but can promote aging. "Care-taking" tumor suppressors like SIRT3 protect against DNA damage, which may result in protection against both aging and cancer. Katharine Brown, Stephanie Xie, Xiaolei Qiu, Mary Mohrin, Jiyung Shin, Yufei Liu, Dan Zhang, David T. Scadden , and Danica Chen ;SIRT3 Reverses Aging-Associated Degeneration; Cell Reports, doi:10.1016/j.celrep.2013.01.005
  • 46. ―Can’t see, can’t hear, can’t walk, but at least I can drive
  • 47. Why Is Driving an Issue?  Automobile crashes are the third leading cause of death and injury in the United States with 40,000 to 50, 000 people killed in about 2 million accidents per year.  In 2001-2002 drivers over the age of 75 had a higher rate of fatal accidents nationwide. This problem is expected to grow because by 2024, one in four U.S. drivers will be over age 65. National Older Driver Research and Training Center
  • 48. Crashes by Driver Age (Source: Cerrelli, 1998)
  • 50. AD was added to the list of the disorders that may make driving hazardous California is one of the six states in the Nation with mandatory reporting of persons with disorders that may make driving hazardous, including Alzheimer’s disease.
  • 51. California Health and Safety Code Section 103900  They are specific to physicians and surgeons per section 103900 of the Health and Safety Code.  The physicians who reports a patient diagnosed with a disorder characterized by lapses of consciousness, according to the Health and Safety code 103900, shall not be civilly or criminally liable to any patient for making the report.
  • 52. Liability Physicians are considered negligent if they do not inform patients of medications and medical conditions that can impair driving 1. Physicians may be held liable for civil damages if they clearly failed to report an impaired driver who causes a MVC. 2. Immunity is granted to the physician if the patient is reported prior to a MVC. 3. Document all referrals, recommendations, conversations, and reports (e.g. copy of a driver retirement letter and “do not drive” prescription).
  • 53. Reporting to the local health authority 2802 AD and related disorders. Means those illnesses that damage the brain causing irreversible, progressive, confusion, disorientation, loss of memory and judgment. 2806 Disorders characterized by lapses of consciousness. Loss of consciousness or a marked reduction of alertness or responsiveness to external stimuli, inability to perform one or more ADLs, the impairment of the sensory motor functions used to operate a motor vehicle California Code of Regulations (CCR) title 17 sub-chapter 2.5― Disorders characterized by lapses of consciousness‖ sections 2800-2812.