AGING
Ed Friedlander, M.D., Pathologist
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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

I am active in HealthTap, which provides free medical guidance from your cell phone. There is also a fee site at www.afraidtoask.com.


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Freely have you received, give freely With one of four large boxes of "Pathguy" replies.

I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.

Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.

I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:

Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of requests for information weekly, all as a public service.

Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

If you're a private individual who's enjoyed this site, and want to say, "Thank you, Ed!", then what I'd like best is a contribution to the Episcopalian home for abandoned, neglected, and abused kids in Nevada:

I've spent time there and they are good. Write "Thanks Ed" on your check.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.

During the eighteen years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at William Carey for making it still possible, and my teaching assistants over the years.

Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!

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Preventing "F"'s: For Teachers!
Medical Dictionary

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We grow too soon old and too late smart.

He who is ripe only in years is called "grown old in vain". He in whom dwell truth, virtue, non-violence, restraint, control -- he who is free from impurity and is wise, he is called an elder.

I grow old ever learning many things.

Someone asked Sophocles [when he was 90], "How do you feel now about sex? Are you still able to have a woman?" He replied, "Hush, man; most gladly indeed am I rid of it all, as though I had escaped from a mad and savage master."

You shall stand up before a grey-haired person, and honor the presence of an old person.

Let your body go in the service of others.

Age does not bring wisdom. Often it merely changes simple stupidity into arrogant conceit. Its only advantage is that it spans change. A young person sees the world as a still picture, immutable. An old person knows that it is a moving picture, forever changing.

Not so much to add years to life, as to add life to years.

Grow old with me!
The best is yet to be,
The last of life, for which the first was made:
Our times are in His hand
Who said, "A whole I planned",
Youth shows but half; trust God:see all, nor be afraid.

May you live as long as you want to. May you want to as long as you live.

Oh to be seventy again!

LEARNING OBJECTIVES

KCUMB Students
"Big Robbins" -- Cell Injury
Lectures follow Textbook

QUIZBANK

INTRODUCTION

    Shakespeare's Hamlet reflected that it is a "calamity" to live too long.

    In the coming years, you will learn a great deal about aging, both from your patients and your own experience. You'll be asked about "anti-aging therapies" (Hosp. Pract. 36: 43, 2001). Since the 1950's I've watched dozens of anti-aging schemes turn out to be expensive failures. Hormone replacement (as appropriate) and physical exercise help older folks far more than anything else we've discovered, but even these do not slow aging itself. As more people live longer, the numbers and percentages of elderly people will increase. This also means more disabled people (Am. J. Pub. Health 81: 443, 1991).

    It is almost impossible to predict who will and will not thrive during the later years (Am. J. Pub. Health 81: 63, 1991), though people can stack the odds in their favor (live longer, less disability at the end) by not smoking, by exercising, and by staying slender in middle age (NEJM 338: 1035, 1998). The implications of this to the health care provider are substantial.


Van Gogh, On the Threshold of Eternity

CELLULAR AGING

AGING OF ORGANS AND SYSTEMS

Robert Redford
Still fit at age 64

Sylvester Stallone
Age 65; looks fit
hair's dyed

Chuck Norris
Still fit at around 50

Charles Bronson
Still fit over age 50

Harrison Ford
Still fit at age 58

Clint Eastwood
Still fit at age 70

Dennis Quaid
Still fit at age 50

Kurt Russell
Still fit at age 47

Thomas Haden Church
Still fit at age 47

Jack Lalanne
Still fit at age 84

Tom Cruise
Still fit at age 48

Matthew McConaughey
Still fit at age 44

Brad Pitt
Still fit at age 50

{25015} senile atrophy of the skin

DISEASES OF AGING

"SYNDROMES OF ACCELERATED AGING"

    CLASSIC PROGERIA (* Hutchinson-Gilford syndrome) is a disease in which patients "appear to age too rapidly".

      This is now known to be a mutation in the lamin A gene (LMNA; * thanks once again, Dr. Collins); the abnormal protein is "progerin" (J. Clin. Inv. 121: 2833, 2011). This is the locus for six other known distinct syndromes (including an "atypical Werner's": Lancet 362: 40, 2003). The progeria mutation is almost always the same and always the result of a de-novo mutation in the sperm (Science 300: 1995, 2003). The gene loses fifty base pairs, and the abnormal product is called "progerin".

        * As important proteins within the nucleus, the laminopathies cause altered DNA expression and repair, and perhaps this accounts for the increase in "degenerative disease" such as atherosclerosis in these children (Nat. Med. 11: 718, 2005). The abnormal morphology of the nucleus is best seen in cell culture (loss of all heterochromatin; strange blebbings especially when stained for lamin A; Nat. Med. 11: 440, 2005).

        The illness is so rare that it took the NIH until 2008 to publish a series of 15 patients, further characterizing the syndrome (NEJM 358: 592, 2008).

Hutchinson-Gilford Progeria
Hutchinson-Gilford Progeria, ages 4 and 5

{25627} progeria

NOT THE LAST WORD ABOUT AGING:

Anything you can turn your hand to, do with whatever power you have; for there will be no work, nor reason, nor knowledge, nor wisdom in the grave where you are going.

Ah, great it is / To believe the dream
As we stand in youth / By the starry stream;
But a greater thing / Is to fight life through
And say at the end, / The dream is true!

The National Academy of Sciences mandate for research in aging and training of geriatricians: NEJM 324: 1825, 1991 and Science 252: 1483, 1991. That's nice. One HMO generated a tremendous amount of paperwork "having a specialty team evaluate all its elderly people" without any apparent real-life benefit whatsoever to the patients (NEJM 332: 1345, 1995). By contrast, when a hospital wing actually DOES some common-sense things to help the elderly get around during and after hospitalization, the benefit is striking (NEJM 332: 1338, 1995).

Nursing homes scandals have repeatedly showcased medicine-for-profit at its worst. The politicians' response has been to mandate that many tasks that any decent person could perform be relegated to high-paid people instead. Sorry, Uncle Sam; skill-and-caring isn't the same as educational-level. This cynical "solution", and the attendant bureaucracy, has led to ridiculous increases in the already-high costs of long-term care (JAMA 273: 1376, 1995).

One robust finding is that long-term severe calorie restriction in rats does prolong maximum lifespan, as well as average lifespan. Despite earlier claims of a spectacular increase, the newer studies show a prolongation of only about 10%, and these rats aren't exercising. By contrast, rats in the study that did a lot of aerobic exercise had prolonged average lifespans but the maximum lifespan was not increased (J. Appl. Physiol. 82: 399, 1997). Perhaps body cells undergo fewer divisions in the undernourished, as these rats' telomeres remain longer etc. (J. Geront. A 54: B502, 1999). Cells in these rats have less tendency to undergo apoptosis when stressed (as in the p66(shc)-knockout mouse): Science 305: 390, 2004. Works for roundworms too, though it offers no further benefit for the Dorian Gray strains (Proc. Nat. Acad. Sci. 95: 13091, 1998); current talk is that calorie restriction probably works by way of the IGF-1 receptor. Stay tuned. It's a provocative and well-substantiated claim -- but how productive do you think you'd be if you subsisted on only half of what a healthy person eats today?

* Speaking of roundworms, initial reports are that the anticonvulsants ethosuximide, trimethadione, and one that people don't use slow aging and prolong lifespan in roundworms (Arch. Neur. 63: 491, 2006). Just a pilot study; the neurodegenerative changes of older roundworms seemed to be what was delayed.

* Ask a health food store proprietor how, where, and at what age Old Man Rodale, the founder and guiding light of Prevention Magazine died. Also, his last remarks about his life expectancy....

* "Aging" role-playing game: JAMA 262: 1507, 1989.

Elder abuse and neglect: NEJM 332: 437, 1995; Arch. Path. Lab. Med. 130: 1290, 2006 ("differential diagnosis"). Sometimes this is the revenge for which the child has waited a lifetime; sometimes not; regardless, you need to intervene to protect the old person, Doctor.

For a chilling tale about a group of "immortal" geriatric cases, read Jonathan Swift's account of the "Struldbrugs" in Gulliver's Travels, book III.

The historic Cyrano de Bergerac wrote an early science-fiction piece about a voyage to the moon (published 1657). When a Lunar citizen feels the mind and body wearing out, the community holds a party and the citizen reviews his or her life. If the peers decide the life was a good one, they kill the person. If not, the punishment is old age.

Shakespeare's King Lear (a must-read). Among the homeless mentally ill, the old king finally realizes that....
His jester and King Lear

Andrew Marvell's To His Coy Mistress: Any English poetry anthology.

Shel Silverstein, The Giving Tree

Socrates's allegory of the cave: Plato's Republic.

BIBLIOGRAPHY / FURTHER READING

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Teaching Pathology

Pathological Chess


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