Biology of Ageing (by Dr JB Lim)

The Blogger's note: The following email has been circulated among the e-buddies lately and an insightful response by Dr JB Lim is reproduced below this:

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Ageing Process - Different parts of our body that age at different times.WE all accept that getting older is inevitable, and now leading clinicians have revealed the exact age when different body parts start to decline, most alarming being the brain and lungs.

French doctors have found that the quality of men's sperm starts to deteriorate by 35, so that by the time a man is 45 a third of pregnancies end in miscarriage.

Here, with the help of leading clinicians, Angela Epstein tells the ages when different parts of the body start to lose their battle with time.

BRAIN - Starts ageing at 20.
As we get older, the number of nerve cells - or neurons - in the brain decrease.
We start with around 100 billion, but in our 20s this number starts to decline.
By 40, we could be losing up to 10,000 per day, affecting memory, co-ordination and brain function.

GUT - Starts ageing at 55.
A healthy gut has a good balance between harmful and 'friendly' bacteria. But, levels of friendly bacteria in the gut drop significantly after 55, particularly in the large intestine,says Tom MacDonald, Professor of Immunology at Barts and The London Medical School.
As a result, we suffer from poor digestion and an increased risk of gut disease.
Constipation is more likely as we age, as the flow of digestive juices from the stomach, liver, pancreas and small intestine slows down.

BREASTS - Start ageing at 35.
BY their mid-30s, women's breasts start losing tissue and fat, reducing size and fullness.
Sagging starts properly at 40 and the areola (the area surrounding the nipple) can shrink considerably.

BLADDER - Starts ageing at 65.
Loss of bladder control is more likely when you hit 65.
Women are more vulnerable to bladder problems as, after the menopause, declining estrogen levels make tissues in the urethra - the tube through which urine passes - thinner and weaker, reducing bladder support.
Bladder capacity in an older adult generally is about half that of a younger person - about two cups in a 30-year-old and one cup in a 70-year-old. ....

LUNGS - Start ageing at 20.
Lung capacity slowly starts to decrease from the age of 20.
By the age of 40, some people are already experiencing breathlessness.
This is partly because the muscles and the rib cage which control breathing stiffen up.

VOICE - Starts ageing at 65.
Our voices become quieter and hoarser with age.
The soft tissues in the voice box (larynx) weaken, affecting the pitch, loudness and quality of the voice.
A woman's voice may become huskier and lower in pitch, whereas a man's might become thinner and higher.

EYES - Start ageing at 40.
Glasses are the norm for many over-40s as failing eyesight kicks in - usually long-sightedness, affecting our ability to see objects up close.

HEART - Starts ageing at 40.
The heart pumps blood less effectively around the body as we get older. This is because blood vessels become less elastic, while arteries can harden or become blocked because of fatty deposits forming on the coronary arteries - caused by eating too much saturated fat.
The blood supply to the heart is then reduced, resulting in painful angina.
Men over 45 and women over 55 are at greater risk of a heart attack.

LIVER - Starts ageing at 70.
This is the only organ in the body which seems to defy the aging process.

KIDNEYS - Starts ageing at 50.
With kidneys, the number of filtering units (nephrons) that remove waste from the bloodstream starts to reduce in middle age.

PROSTATE - Starts ageing at 50.
The prostate often becomes enlarged with age, leading to problems such as increased need to urinate, says Professor Roger Kirby, director of the Prostate Centre in London. This is known as benign prostatic hyperplasia and affects half of men over 50, but rarely those under 40. It occurs when the prostate absorbs large amounts of the male sex hormone testosterone, which increases the growth of cells in the prostate. A normal prostate is the size of a walnut, but the condition can increase this to the size of a tangerine. Having regular sex (once a week) may help slow down the growth of cells in the prostate.

BONES - Start ageing at 35.
'Throughout our life, old bone is broken down by cells called osteoclasts and replaced by bone-building cells called osteoblasts - a process called bone turnover,' explains Robert Moots, Professor of Rheumatology at Aintree University Hospital in Liverpool.
Children's bone growth is rapid - the skeleton takes just two years to renew Itself completely.
In adults, this can take ten years.
Until our mid-20s, bone density is still increasing.
But at 35 bone loss begins as part of the natural ageing process.

TEETH - Start ageing at 40.
As we age, we produce less saliva, which washes away bacteria, so teeth and gums are more vulnerable to decay. Receding gums - when tissue is lost from gums around the teeth - is common in adults over 40.

MUSCLES - Start ageing at 30.
Muscle is constantly being built up and broken down, a process which is well balanced in young adults. However, by the time we're 30, breakdown is greater than buildup, explains Professor Robert Moots. Once adults reach 40, they start to lose between 0.5 and 02 per cent of their muscle each year.
Regular exercise can help prevent this.

HEARING - Starts ageing mid-50s.
More than half of people over 60 lose hearing because of their age, according to the Royal National Institute for the Deaf.

SKIN - Starts ageing mid-20s.
The skin starts to age naturally in your mid-20s.

TASTE AND SMELL - Start ageing at 60.
We start out in life with about 10,000 taste buds scattered on the tongue.
This number can halve later in life.
After we turn 60, taste and smell gradually decline, partly as a result of the normal ageing process.

FERTILITY - Starts ageing at 35.
Female fertility begins to decline after 35, as the number and quality of eggs in the ovaries start to fall.
The lining of the womb may become thinner, making it less likely for a fertilised egg to take, and also creating an environment hostile to sperm.

HAIR - Starts ageing at 30.
Male hair loss usually begins in the 30s. Hair is made in tiny pouches just under the skin's surface, known as follices. A hair normally grows from each follicle for about three years, is then shed, and a new hair grows.
Most people will have some grey hair by the age of 35.
When we are young, our hair is coloured by the pigments produced by cells in the hair follicle known as melanocytes.

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Thanks for your e-mail circular, and also soliciting my opinion.

I do not know how Angela Epstein (pic left) with the help of clinicians came to these conclusions on the ages of the organs?
First of all, no scientific reference in the literature was given. They were just unsubstantiated claims. The names of the clinicians and their credentials were also all not given.
Secondly, how did they conduct their studies, namely the methodology (study designs), numbers of subjects in the population under study, the cohorts, whether cross-sectional or longitudinal study, the time frame, gender, age-group, ethnicity, confronting factors, etc…, and importantly the analysis and interpretation of the data. All these vital scientific data were not quoted and given. How could I, as a professional member of the scientific community concur with these claims? It would be highly unprofessional and unethical.
Thirdly, where were their findings published? Inside these junk chain e-mails passed on from one ignorant person to the next ignorant person, inside a newspaper meant for wrapping left-over foods for the garbage-bin the next morning, or were their findings published in a peer-reviewed, international refereed scientific journal. If it was, where is the literature reference?
Fourthly, Angela and her team of doctors are just clinicians. A clinician is a medical doctor who merely practices routine, standard, bedside medicine on his patient in a hospital ward. They are not the type of doctors like their medical colleagues and counterparts who practices investigative, diagnostic and experimental medicine in a medical laboratory using sophisticated, high-tech equipments. These medical researchers are normally also armed with PhDs or other doctorate degrees, and not just a mere MBBS, or MD to assist them in their investigations.
How is it possible for these clinicians by mere routine physical (clinical) examinations give the various ages of the organs, when even medical researchers with their far more sophisticated and in depth knowledge of medical sciences, and who are the frontiers in the advancement of medicine, are not able to exactly measure the dates, age, and life-span of a single organ, let alone compare the ages of various organs? I think Angela and her clinicians are talking nuts.

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As a former senior medical researcher at the prestigious Massachusetts Institute of Technology (MIT) and at Malaysia’s Institute for Medical Research (IMR), and a current Special Medical Adviser to an international pharmaceutical group, I am very sticky about all these claims and chain e-mails, especially on medical and scientific issues.

Let me explain briefly in a very simple and reachable way.

Scientists are not gods:

Albeit it may be true that different systems and organs in the body age at different times, and at different levels, we cannot give exact and specific ages or dictate the life-span to these organs. As medical scientists and doctors we must not pretend to be gods. We are definitely not to give the age, life span of any organ or to tell any person or patient how long more can he / she live? We have absolutely no right to do this. We are absolutely bogus ‘professionals’ if we make such claims.

The Power of Statistics:
We can only extrapolate and roughly guess age and life span based on previous or existing medical statistics. What we do normally is to look at the distribution of occurrences in a histogram. We look at the normal distribution of a set of data and examine how tightly all the various data are clustered around the median (‘average’). There will always be a few individuals who are at both ends of a normal distribution (standard deviation). We use these statistical yardsticks to predict the chances of ageing, morbidity and mortality or risk of any medical events in a set of measured data.
When the observation is tightly bunched together and the bell-shaped curve is steep, as scientists-statisticians, we say that the standard deviation is small. This is the best we can do. We are definitely not gods, semi-gods, magicians, or fortune-tellers as the lay public thinks. We base the estimates loosely on past studies or matured clinical experiences, but best of all, it should be on solid statistics complied over a very large population under study. Scientists and clinicians must rely on data to make an inference, because statistics don’t lie. This is what we call Science, not fortune-telling.

That is the best guess or estimate clinical scientists need rely on, and it should only be based on previous measurements, experiences, and published epidemiological data, and not hear-say and wild guesses. We are not gods or fortune tellers. Even on medical statistics, sometimes this is unpredictable due to varying biological responses from individual to individual. This is clearly shown by the standard deviation clustering around the medium in a histogram distribution. There will always be a small proportion in a population that deviate from the mean or ‘average’ in loose statistical jargon.

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The stupid ignorant public:

But the ignorant public thinks we are semi-gods to be able to ‘predict’ the prognosis of a disease, the age of an organ, or when we shall die. Stupid, stupid, public! Absolutely only God and Mother Nature can pass the death sentence, and no one else. Once again we must not pretend to be gods, maybe bogus gods, yes, and a big yes.

An almost impossible study:

Such a study on ageing and time of death to any organ in humans is exceedingly difficult to undertake, if not impossible to conduct. No human is going to donate their various organs for such unethical study, and no pathologist can determine age-differentiation of the cells and tissues based on histopathology alone.

Neither can physiologists match and compare physiological functions of one organ with another. They can only at best, measure or evaluate degrees of physiological functions (not age) of just one organ, say of the heart or lungs over a time scale. Physiologists can measure the efficacy of renal function (example) by looking at the filtration rate, urinary and plasma concentrations of some physiologically important substances (glucose, Na+, urea, creatinine), but these only measure the functionality of the kidneys, and not the age. How can a clinician claim he can do this by mere clinical examination? It beats me. Even a highly qualified renal physiologist cannot determine the age of the kidney? A rough guess perhaps, based on its size, morphology, and cellular structures (histology). It beats me. The same criteria for the measurements of cardiac, lungs, liver and other organ functions without going into medical and physiological details.

One of my university degrees is in physiology, some biochemistry and pharmacology thrown in as one, but despite my academic training, I do not know of any scientific procedure that can measure age or life span of any organ as claimed by Angela Epstein and his clinicians? As far as I know, no literature has been published on such a study. I think all these claims circulating around in e-mails are by bogus people.

Factors that dictates:

There are many factors that determine ageing, among them our genetic make up, our diet and nutrition, our exposure to damaging environments and agents such as free radicals, toxins, radiation, drugs, chemical injuries, metabolites, endogenous and exogenous stresses, and also the body’s compensatory repair mechanisms that enables it to repair all damages especially the DNA. It is estimated there are about 10 million molecular lesions per cell per day, and this escalates with the ageing process, because the body fails to repair the continuous damages every second in our life, and our organs as a whole.

An example:

For instance, it was stated in the e-mail claim that the “LIVER - starts ageing at 70. This is the only organ in the body which seems to defy the aging process”.

The above statement is not entirely true. While it is true that the liver is the only organ in the body that can regenerate itself when injured, and hence ‘live’ longer, the opposite is also true. If the liver, the only detoxifying organ in the body, is constantly subjected to powerful toxins and carcinogens like aflatoxins, and other mycotoxins, alcohol through alcoholism or when infected by groups of viruses such as HAV, HBV, HCV and HEV that cause various types of infective hepatitis, then the liver is the only organ that is going to go first. Its life span will drastically be cut far shorter than the brain or skin (example).

Every cell in our body has a programmable cell death called apoptosis (cellular suicide). For instance, the skin cells live 28 days and then die. Cells lining the cheeks of our mouth and intestines live 48 hours, and the red blood cells have a life span of 120 days.

But when cells become cancerous, they live forever. They lose apoptosis and override the cellular programme (cellular signaling) to self-destruct. Probably only embryonic stem cells and cancer cells do not die under normal cell-signaling mechanisms, but not the liver. The liver can be damaged by poisons, drugs, chemical agents and viruses, and they do lose its functionality, age and die from cirrhosis, and hepatocellular carcinoma (cancer of the liver).

Another study shows cytokines lymphotoxin can lead to liver cancer. The liver dies from liver failure, and the whole body dies with it. The statement given in the e-mail circular is not true.

Chromosomes and DNA:

Ageing to various parts of the body also depends on the chromosomal make-up. An individual with chromosomal defect such as Down Syndrome can expect to have very low life expectancy to almost all his organs especially in the 1920s, albeit advancement in medical sciences has extended the life expectancy of Down victims. There is a chromosomal structure at the end of each chromosome that dictates how long each cell is going to age and live. This protein structure sitting at the end of each chromosome actually dictates the life span of every cell, the life span of an organ which contains these specific and specialized cells.

A Nobel Prize discovery:

This was discovered jointly by three scientists; Elizabeth Blackburn, Carol Greider, and Jack Szostak who subsequently won the Nobel Prize in Medicine or Physiology. They were honored for characterizing the telomeres, specialized structures at the loose ends of the DNA structure. These loose ends of our DNA are necessary to determine if the cell (of an organ) is to continue to divide or just age and die off. This has nothing to do with any specific organ, whether heart, lungs, spleen, kidneys, skin, etc. It is the ability for another enzyme called telomerase that adds DNA sequence repeats ("TTAGGG" in human and all vertebrates) to the 3' end of DNA strands in the telomere regions, and that dictates it ageing and life-span. It is as simple as that.

This discovery has great and profound implication in medicine, as it is the blue print that decides everything from aging to cancer. It has nothing to do with individual organs as these clinicians think. They are talking nuts.

Nutrition:

The life span of any organ also depends on the nutritional status of an individual. For instance, a child in a state of severe protein deficiency, as shown in many cases of infants in Africa, will suffer from a nutritional disease called kwashiorkor. This is a very acute form of childhood protein-energy malnutrition clinically characterized by edema (water retention in the tissues) irritability, anorexia (refusal to eat), ulcerating dermatoses (skin ulceration), and hepatomegaly (enlarged liver) with fatty infiltrates.

The presence of edema caused by poor nutrition defines kwashiorkor. Kwashiorkor was thought to be caused by insufficient protein consumption but with sufficient calorie intake, distinguishing it from marasmus. More recently, micronutrient and antioxidant deficiencies have come to be recognized as contributory. In the event of protein and caloric deficiency (protein-energy malnutrition), the clinical characteristics are presented as marasmic-kwashiokor which features both syndromes.

In such cases, it is the protein mass (muscles) that ages and goes first, and not the hearing, bones, bladder, prostate (males), or any of the organs as mentioned in your, or Angela Epstein and her team of clinicians e-mail. The other exception is the liver that suffers from hepatic steatosis (fatty infiltration of the liver) in the event of severe protein deficiency. The liver does age and fail in the event of serve kwashiorkor. But these clinicians (medical doctors) claim that the liver only age and dies at age 70? I think they are talking nutty medicine or nutty physiology.

We should get our clinical priorities right. This is the first step, the hallmark in the practice of good, ethical medicine or the gold standard in the practice of nutrition. You cannot use the normal physiology of ageing to predict the outcome of a pathological event. It is the internal and external influencing factors that prescribe the outcome of a pathology or the pathogenesis of ageing.

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Not just what you eat, but also what you don’t:

Ageing and longevity also depends not just ‘what you eat’ as stated by you, but also on ‘what you do not eat’.

Other than obvious poisons, medications, and food contaminants ingested that damages literally almost all organs, especially the liver that suffers the greatest insult having to deal with them, followed by the kidneys that have to excrete the metabolites (end products of metabolism and detoxification by the liver, especially drugs (pharmacokinetics), all these agents damage and age every organ by varying degrees, depending on the absorption rates, T 50 (half-life), and retention time, and the kinetics of the toxins absorbed, and its distribution.

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Drug toxicity:

For instance, sedation drugs such as chlorpromazine, thioridazine, indicated for psychotic illness, can cause retinal pigmentation, corneal and lens opacities if the dose is too high, prolonged, or both. Thus the eyes will age and go first, and not the smell, taste, heart or voice. It all depends on the agents (drugs and toxins) an individual is habitually exposed to. Each agent affects different organs differently, specifically, and in varying degrees of sensitivity (‘specificity and sensitivity’ in pharmacological terminology).
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Sub-nutrition, ageing and longevity:

As far back as in 1934, three researchers, Mary Crowell and Clive McCay of Cornell University has shown that laboratory rats fed a severely reduced calorie diet while maintaining micronutrient levels resulted in life spans of up to twice as long as otherwise expected. These interesting discoveries were followed up in detail by a series of experiments with mice conducted by Roy Walford and his student Richard Weindruch.
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My Jewish Mentors:

This information was taught to us by two of our highly intelligent and exceedingly knowledgeable Jewish Professors at the Universities of London and Cambridge when we were postgraduate students there way back in the 1960s. The Jews are an astonishingly brilliant race. The Jews are the ones that win almost all the Nobel Prizes ever since the Swedish Nobel Prize Committee started these highly prestigious academic awards. The Jews head almost all the university academic departments in America, Europe and Great Britain, let alone in Israel. That race is really great and very powerful. They are truly God chosen ones. So this piece of knowledge I got was from my Jewish Professors at English universities, and it is not new to us.

A lot of Malaysians sent to England on a freely give away Malaysian scholarships by the thousands were also taught by the Jews, but I am unsure of their quality when they return to Malaysia. I was on a British Government scholarship, entirely on academic merit, and not hand-outs, albeit I am not a British citizen. It is my cherished gratitude to them.

Further findings:
In 1986, Weindruch reported that restricting the calorie intake of laboratory mice proportionally increased their life span compared to a group of mice fed a normal diet. What was interesting is the calorie-restricted mice also maintained youthful appearances and activity levels longer and showed delays in age-related diseases. The results of the many experiments by Walford and Weindruch were summarized in their book The Retardation of Aging and Disease by Dietary Restriction (1988).

You can get this publication from a publisher (ISBN 0-398-05496-7) if you are interested in the dietary modality to youthfulness and longevity. I recommend this publication. Maybe find it at MPH, Kinokuniya, or order it straight online from Amazon.

Acceptance:

The findings have since been accepted by the scientific community, and are applied to a range of other animals. Researchers in an on-going study investigating the possibility of parallel physiological links in humans, but it will take another generation of 35 years to know the findings.

An ABC analogy:
This is very simple to understand with this analogy. If you continue to pump fuel (food) into an engine (body) to force it to run continuously without rest, the engine’s life span will be greatly shorten due to wear and tear. But if you restrict the supply of fuel to the engine, the engine will remain as good as brand new and will last a long time. It is as simple to understand as that without going into the highly complexities of biochemistries.

Caloric restriction or anti-ageing hormones
In the meantime, many health conscious people are already independently adopting the practice of calorie restriction in the hope of prolonging longevity and the prevention of age-related chronic diseases. I wish them well.

Others attempt short-cuts with human growth hormone (HGH) and other anti-aging hormones (DHEA, oestrogen, melatonin, testosterone and other hormones of the pituitary as their anti-ageing therapies. Which is which? They are ‘mengxiang’ (Mandarin: dreams).

Brief conclusion:

Thus back to what I said, it is not just, you are what you eat, as many people think, but importantly you are also what you don’t wish to eat that make a difference to your risk of being a candidate to degenerative age-related diseases that prescribes your human genetic life span.

I hope this answers your question.

lim ju boo5:50 a.m.
The 4th Day of Chinese New Year
The Year of The Rabbit 2011

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The blogger is delighted and feels flattered to have received Dr Lim's feedback on this posting as follows:

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Monday, 14 February, 2011 2:08 AM

Dear Ir. Lau,
You are good. Very good with your blog presentation with so many pictures, graphics, including the histogram on distribution and its standard deviation, and with music added in also. You are really an artist besides being an engineer. Godd show lah. I must in future give you all my plain b & w stories to make it more colouful. Maybe we can co-author together.

Confucius said "a picture is better than 1000 words" and I think so myself after seeing how to added pictures and illustrations in.

I can never with so colourful and pictureque with my blog (pic left http://scientificlogic.blogspot.com/). I have never tried putting pictures in, except just plain dull text. I need to use the technique you told me, and see if it works. Maybe I have not attempted to try out the features it offers.

Anyway, I shall continue to provide you with dull stories for you to colour it.

Thanks

jb lim