A Research Guide for Students by I Lee

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Genetics: As Time Ticks On
(Genetics of Human Aging)

By Dr. Peter W. Kujtan, B.Sc., M.D., Ph.D.

Portrait of Dr. Peter W. Kujtan, supplied 2005
Dr. Peter W. Kujtan

This week, we start a multi-part series on aging.

Topics of discussion will center on golden year club members, time-testers, pensioners, seasoned survivors, snow birds, and retirees. I have had many opportunities to address audiences drawn from this ever-increasing demographic and still find myself lost at how best to address this group. How do you know whom to include in this bunch? In general, they have been around the block and learned a thing or two on the way. Youth and vigor are always on their mind. The only thing worse than a four-letter word is a three-letter word spelt O-L-D as Fred Hilditch's gang was quick to point out. Things once clear are now blurry, open things become blocked, and some things remain firm but in the wrong places. Dryness replaces wetness and funerals begin to outnumber weddings.

As we desiccate, shrink and shrivel, it is worthwhile to attempt to understand how this process functions. It is your best chance to stay ahead of it. The process of growing old is probably better referred to as senescence. Some people now believe that "aging" is solely due to an accumulation of damage to your DNA resulting in loss of the ability for your cells to divide. They feel that free radicals are the main culprits. These are molecules such as super oxide and nitric oxide with unpaired electrons in their outer orbits. They are highly reactive and can damage proteins, lipids and especially DNA. They often result from our poor food choices.

If it were as simple as accumulated DNA damage, then we would expect to see a wide range of older people. Currently, there is an upper limit to human chronological age. Our maximum life span seems to be between 115-120 years. Human cells lose the ability to duplicate themselves after about fifty repetitions. Interestingly, this magic number of 50 seems to hold steady across the animal kingdom. The cells in birds with a two-year lifespan or those in a 150 year old giant tortoise lose abilities after fifty multiplications. As we slowly lose that ability, things start to look it. Another widely accepted theory of aging suggests that certain cells are preprogrammed to only last a certain amount of time. The programming can vary within your body. For example, the female reproductive organs seem to age the fastest and lose their function by age fifty. Menopause is a relatively new concept in human history. For most of the last millennium, women rarely made it to that age so that cellular preprogramming may not have mattered. But even today, women tend to outlive men. So, the loss of sex hormones may be linked to aging. Historically, eunuchs, who are males without testes, tended to live longer as do sterilized cats and dogs. The commonest cause of death of the elderly in our culture is cardiovascular disease. Estrogen is a sex hormone that until recently has been naturally augmented when ovarian supplies fail. In addition to the numerous beneficial actions, recent data has noted a slight increase in cardiovascular problems with its use.

The advent of better sanitation and medical care has increased our life expectancy significantly. Curing disease will get more people closer to the 120 maximum, but not beyond. Living a perfect life punctuated with the perfect diet can only get us so far. With a lot more older folks around, someone had to study and look after them, so a whole new field of medicine called Geriatrics came to be. Interestingly, it is accepted that more and more people are not dying of any particular disease, but simply "old age". Cellular repair mechanisms in essential organs such as heart and lung cease to function. This lends support to the genetic program theory of cell death. It also provides hope. By unlocking the code for the cascade of proteins or enzymes that terminate cell propagation we might be able to block it. This might result in an unlimited ability to repair and multiply and raise life expectancy into the hundreds of years.

How and Why We Age
by Leonard Hayflick Ph.D.
Jan 23, 1996

How and Why We Age (Paperback) by Leonard Hayflick, Ph.D.
    Maximum Life Span
by Roy L. Walford M.D.
Jan 1, 1981

Maximum Life Span by Roy L. Walford, M.D.
    Lifespan: Why We Age
and Why We Don't Have To
by David A. Sinclair PhD,
and Matthew D. LaPlante,
Sep 10, 2019

Lifespan: Why We Age - and Why We Don't Have To,  Hardcover - Illustrated, September 10, 2019 by David A. Sinclair PhD, and Matthew D. LaPlante

Related resources:

36 Living Actors Over 80 Years Old | Then And Now 2019. YouTube video, 10:08 min. Published by All Things Famous, Apr 7, 2019.

Mechanisms of Aging by Ben Best. An excellent, lengthy and detailed essay started by Ben in the mid-1990s and has since been revised every year.
See also Articles about Life Extension by Ben Best.

What Do We Know About Healthy Aging? From National Institute on Aging (NIA), National Institutes of Health (NIH). Topics include: Get moving: Exercise and physical activity
Healthy eating: Make smart food choices
Getting a good night's sleep
Quit smoking
Alcohol and other substances
Go to the doctor regularly
Social isolation and loneliness
Depression and overall mood
Leisure activities and hobbies
How different factors affect cognitive health
How cognitive training affects health outcomes ● Tips to Boost Your Health as You Age from National Institute on Aging (NIA), National Institutes of Health (NIH). Small lifestyle changes may go a long way in supporting healthy aging. Learn about steps you can take to help support your physical, mental, and cognitive well-being later in life.

11 ways to reduce premature skin aging from American Academy of Dermatology (AAD), Feb 24, 2021.

Anti-ageing: Is it possible, and would we want it? By Peter Ray Allison, BBC Future, Oct 2, 2017. Eternal youth has been a human preoccupation for millennia. But what would happen if we could actually halt the ageing process?

Life Expectancy Calculator from Project Big Life.ca.

Lifespan Calculator. How long you have already lived is one of the best predictors of how long you may live. Answer 13 questions to find out how long you're predicted to live.

Life Span. 1. The duration of life of an individual. 2. The normal or average duration of life of members of a given species.
Medical definition: 1. A lifetime. 2. The average or maximum length of time an organism, a material, or an object can be expected to survive or last - from American Heritage® Medical Dictionary.

Lifespan from Science Direct. Lifespan is defined as the maximum number of years that a human can live, while life expectancy is the average total number of years that a human achieves ~ A Roadmap to Non-hematopoietic Stem Cell-Based Therapeutics: From the Bench to the Clinic, edited by Xiao-Dong Chen, published in 2019 by Elsevier Inc. Reviews of numerous books on Lifespan and Aging:
Developmental Psychology by R.A. Dixon, in International Encyclopedia of the Social & Behavioral Sciences, 2001.
Life Span Theory by W.J. Hoyer, in Encyclopedia of Gerontology (Second Edition), 2007.
The Budding and Fission Yeast Model Systems for Aging Biology by Kurt W. Runge, Haitao Zhang, in Conn's Handbook of Models for Human Aging (Second Edition), 2018.
Mechanisms of Action of Curcumin on Aging by Ana C.Carvalho, Andreia C. Gomes, Cristina Pereira-Wilson, and Cristovao F. Lima, in Molecular Basis of Nutrition and Aging, 2016.
Genetics of Aging by M. Kaeberlein, in Brenner's Encyclopedia of Genetics (Second Edition), 2013. ● What Is Aging? from senescence.info. "Aging is one of the most complex biological processes, whose definition is intrinsically related to its phenotype ... Aging has been defined as the collection of changes that render human beings progressively more likely to die (Medawar, 1952)."

Life expectancy from Wikipedia, the free encyclopedia. Definition of Life expectancy: The average number of years a person can expect to live, or the average number of years of life remaining at a given age.

Maximum life span from Wikipedia, the free encyclopedia.

How Long Will I Live? Calculate Life Expectancy. Calculator developed by Professors at the University of Pennsylvania. Find out your customized life expectancy based on 400,000 NIH data samples and a short quiz about your lifestyle.
How Long Will I Live? (Short quiz of 4 questions).
How Long Will You Live? How Calculations Are Done.

Life Expectancy Calculator from Living to 100.

senescence.info. An educational resource on the science of aging.

Differences Between Human Life Span and Expectancy by Mark Stibich, PhD, Medically reviewed by Rochelle Collins, DO, May 5, 2020. While the term lifespan refers to the maximum number of years an individual can live, life expectancy refers to an estimate or an average number of years a person can expect to live.

Life expectancy in Canada from World Life Expectancy. Tom LeDuc, the founder of Global Life Partners, is one of America's top mortality marketing strategists. World Life Expectancy is an example of his profound belief in being willing to give before you receive.

Do you want to live to be 100? Answers from older people by Helena Karppinen, Marja-Liisa Laakkonen, Timo E. Strandberg, Emmi A. Huohvanainen, and Kaisu H. Pitkala, in Age and Ageing, Vol 45, Iss 4, July 2016, Pages 543?549, Published: 13 April 2016.

Those Who Live to 100 Have These Things in Common by Deborah Kan, Being Patient, Jan 11, 2019. Jason Prall, director of The Longevity Project, traveled to nine countries and three continents, interviewing some of the world's healthiest centenarians. Prall explored what it takes to live past 100 years old and whether it's possible to reach that age while maintaining peak health. He studied how their lifestyle, environment and mindset increases longevity.

What is the oldest living thing on earth? Who has the secrets to longevity? By jstankevicz, from HubPages.

The Oldest Living Things in the World: Photographs by Rachel Sussman. Images include a 2,200 year-old Patagonian Cypress, 3,000 year-old lichen in Greenland, and an 80,000 year-old clonal colony of Quaking Aspens, with Location Map of living things, 2000 years old and older.

Life extension from Wikipedia.

Who's Afraid of Life Extension? by Harry R. Moody, Institute for Human Values in Aging, International Longevity Center-USA. Discusses two forms of life extensions: 1. "Weak" life extension means increased average life expectancy ... from 76 to 100, combined with compressed morbidity, with maximum lifespan remaining unchanged (at around 120 years). 2. "Strong" life extension means dramatically increased life expectancy ... from 76 to 200 years, with continued compression of morbidity, and maximum lifespan rising to something like 240 years.

Who's Afraid of Life Extension? From Fight Aging, Aug 1, 2004.

The Experience of Aging and Perceptions of "Aging Well" Among Older Migrants in the Netherlands by Nina Conkova, PhD, Jolanda Lindenberg, PhD. The Gerontologist, Vol 60, Iss 2, Mar 2020, Pages 270-278. Published: Sep 30, 2019.

The Aging Experience: Diversity and Commonality across Cultures by Jennie Keith, Christine L. Fry, Anthony P. Glascock, Charlotte Ikels, Jeanette Dickerson-Putman, Henry C. Harpending, and Patricia Draper, SAGE Publications, Inc., 1994. Online pub date: June 19, 2012.

Can People Really Die of Old Age? The answer is no. People don't die of old age. Article by Chris Weller, The Unexamined Life, Medical Daily, Jan 21, 2015. What is aging? Being Older (and Braver), Can we live forever?

Senescence from Wikipedia, the free encyclopedia. Senescence is a process induced by evolution into an organism's genetic make up so that it may live to its healthiest until its reproductive age and die slowly and gradually thereafter ... The word senescence is derived from the Latin word senex, meaning "old man" or "old age" or "advanced in age".

AnAge: The Animal Ageing and Longevity Database. The Human Ageing Genomic Resources (HAGR) is a collection of databases and tools designed to help researchers understand the genetics of human ageing through a combination of functional genomics and evolutionary biology.

The Evolution of Ageing from Human Ageing Genomic Resources (HAGR). "Our aim in this project is to study the events, including genetic changes, shaping longevity in different lineages to help understand why different species age at different paces."

Species with Negligible Senescence. List of seven species that appear not to age, e.g. Eastern box turtle - Longevity: 138, Rougheye rockfish - Longevity: 205, Ocean quahog - Longevity: 400, Great Basin bristlecone pine - Longevity: 4,731 years.

Evolution of ageing from Wikipedia, the free encyclopedia. "Enquiry into the evolution of ageing aims to explain why almost all living things weaken and die with age . . . The evolutionary origin of senescence remains a fundamental unsolved problem in biology."

The Evolutionary Theory of Aging from senescence.info.

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