NORMAL AGINGDefinition of aging, Life expectancy/maximum lifespan, cellular and organismal aging, Rapamycin, progeria, telomeres, 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 PsychosocialDevelopment

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 moreImportant-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, telomerase 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 LacksHe-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 informpatients of medications and medical conditions that canimpair 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” sections2800-2812.