Ageing

Reliefs

			mind active and by maintaining a sensible diet. The record holder of maximum longevity belongs to France's Jeanne Calment (see Figure 10a), who lived to be 122 years and 164 days old. Longevity ran in her family. Calment's mother lived until she was 86 and her father until he was 94. Her personal outlook of life may also contribute; it is said that she was immune to stress. She was once quoted: "If you can't do anything about it, don't worry about it."
Figure 09 Fountain of Youth	Figure 10a Jeanne Calment	Figure 10b Longevity Unlimited	A 2018 study suggests that the "risk of death" levels off to about 50 - 50 after age 105 (Figure 10b). This is revealed by statistical analysis of 3836 Italians aged 105 and older.

Defence Against Free Radicals and Diets - To increase the defence against these ROS, it is suggested that consumption of special kinds of foods, herbs, and dietary supplements (including vitamins C and E, beta carotene and selenium) will scavenge excess free-radicals and provide raw materials necessary for the body to produce antioxidant enzymes. Many of the foods high in antioxidants are vegetable matter. Tomatoes, broccoli, cauliflower, peppers...are all excellent choices (Figure 11a). The key is to focus on eating those fruits and vegetables that have rich hues of color. These are high in what are known as phytonutrients. Phytonutrients are nutrients concentrated in the skins of many vegetables and fruits, and are responsible for not just their color, but scent, and flavor as well. Phytonutrients are the best antioxidant foods that exist in nature. Clinical trials are now revealing that phytonutrients can enhance the strength of the immune system, and may play a role in preventing certain cancers. Blueberries and bilberries are two of the best antioxidant foods you can buy -- very rich in phytonutrients. However, a 2013 study shows that different kind of diets (healthy or un-healthy) has no effect on aging or related diseases once the person has passed 75 year old.

Figure 11a Vegetables [view large image]

(see a brief report and also more detail from the links in the report)

Study in 2006 reveals that antioxidants are beneficial only from natural food sources. Double-blind randomised controlled trials indicated that supplements failed to pass the test time and again. At best, they are a waste of time and money. At worst they could be harmful. For examples, beta carotene supplement is found to increase the risk of lung cancer in smokers; vitamin C may accelerate atherosclerosis in some people with diabetes; vitamin E is clearly doing something, but it loses its antioxidant power inside the body. These vitamins are useful only in people with such deficiency already. No one knows for sure why the supplements do not work. One explanation argues that because the antioxidant in fruits and vegetables are bound into tough, fibrous material, they hang around in the stomach and colon, where they can neutralise free radicals. Figure 11b lists the top 20 antioxidant foodstuffs rated by the US Department of Agriculture in 2004. TE = Trolox Equivalents. Trolox is a vitamin E derivative which is used as the standard benchmark for antioxidant power. By way of comparison, 100g of wholegrain bread contains 1421 mol of TE.

Figure 11b Antioxidants

Table 05 Link Between Foods and Genes

pH Level - Similar to the body temperature, which has to be maintained at 98.6^o F; the pH level in the various body fluids are kept at a narrow range (see Figure 12a) for the metabolic reactions to proceed properly. Figure 12b shows the pH levels for various substances (pH = 7.0 is neutral, pH < 7.0 is acidic, pH > 7.0 is alkaline). The Saliva pH test is a simple test to measure the susceptibility to cancer, heart disease, osteoporosis, arthritis, and many other degenerative diseases. In the saliva test (with pH paper), most children are dark blue (colour of the pH paper), a pH of 7.5; over half of adults are green-yellow, a pH of 6.5 or lower, reflecting the calcium deficiency of aging and lifestyle defects; cancer patients usually register bright yellow, a pH of 4.5, especially when the disease becomes terminal.

		You can test the pH level of your saliva or urine at home with pH paper strips. Figure 12c shows the colour index for standard pH paper corresponding to the pH scale. An acidic pH can occur from, an acid forming diet, emotional stress, toxic overload, and/or immune reactions or any process that deprives the cells of oxygen and other nutrients. The body will try to compensate for acidic pH by using alkaline minerals. If the diet does not contain enough minerals to compensate, a build up of acids in the cells will occur. The body has three mechanisms for the maintenance of normal acid-base balance:
Figure 12a Body Fluid pH Levels [view large image]	Figure 12b pH Scale

1. Rapid chemical buffering - The balance is restored by buffers in the blood. The buffers are supplied by withdrawing minerals from other organs including the bones, soft tissues, body fluids and saliva. This occurs almost instantly but buffers are rapidly exhausted, requiring the elimination of hydrogen ions to remain effective.
2. Respiratory compensation - This mechanism uses breathing to eliminate carbon dioxide (which produces acid). The respiratory center in the brainstem responds rapidly to changes in CSF (Cerebrospinal Fluid) pH (normally at 7.3). Thus, a change in plasma pH results in a change in ventilation within minutes.
3. Renal compensation - The kidneys respond to disturbances in acid-base balance by altering the amount of bicarbonate reabsorbed and hydrogen ions excreted. However, it may take up to 2 days for bicarbonate concentration to reach a new equilibrium.

		blueberries, plums, prunes, cranberries) are alkaline. Some dietitians recommand as much as 80% of the diet to be alkalizing foods. Many websites post complete listing on alkaline and acidic foods (Figure 12d). A comparison of the pH food chart with the list of antioxidants (Figure 11b) shows that high alkaline foods may not be good antioxidants and vice versa. A possible strategy is to consume a little bit of each as a compromise between the conflicting benefits.
Figure 12c Colour Index for pH Paper	Figure 12d pH Food Chart

Calorie Restriction - Recently, it is observed that the most efficient way to delay aging is through caloric restriction. It is found that healthy and long-lived mice and rats are produced by reducing 30 - 40 percent the calories in the animal's diet (Figure 12e). It seems that the animals have switched their metabolism from a pro-growth mode to a pro-repair mode. Studies have shown that caloric restriction triggers a pathway that produces the Sir2 enzyme, which prolongs the life of yeast and worm. The latest research tries to manipulate the level of IGF-1 (insulin-like growth factor-1) protein so that people can maintain the pro-repair mode without dietary restriction.

Figure 12e Calories Restirction [view large image]

		Further study of TOR is published in a January 2012 "Scientific American" article. It is found that TOR is beneficial to the growth of organisms when resources are plentiful, its inhibition reverts the mode to cell maintenance and repair when resources are scarce (Figure 12f1). The growth mode becomes a problem in late life when too much cell proliferation leads to age-associated diseases. Experiments show that intervention to curtail TOR's activity prolongs life in organisms including yeast, worm, fly, and mouse (Figure 12f2). One theory suggests that evolution doesn't care about old age because there is no such thing in nature, where life would be terminated by predators, infections, accidents, ... before reaching such stage.
Figure 12f1 TOR's Side 1 - Young Age	Figure 12f2 TOR's Side 2 - Old Age

lifestyle to an advanced age even in the mentally and physically disabled. Estimates suggest that up to half of the physical decline associated with old age may be due to lack of physical activity. Factors such as muscle mass, bone strength and joint flexibility can be improved dramatically with regular exercise. Physical activity helps prevent the development of diseases such as cardiovascular disease, type II diabetes, osteoporosis, arthritis, colon cancer, obesity and injury prevention (by maintaining muscle strength). Gentle exercise helps make the bones stronger and less likely to break. A government recommendation urges the seniors to take part in 30 minutes of moderate physical activity, such as a brisk walk on most days of the week. Recently in 2004, it is found that the activity level of skeletal muscle modulates a range of genes, which produce dramatic molecular changes - and keep us healthy. The skeletal muscle is the largest single tissue type in the human body. We have more than 640 muscles, accounting for between 30 and 40 precent of total body weight. It uses as much as 25% of the energy consumed by the body at rest. Skeletal muscle continuously adjusts its composition to meet the acute or chronic demands placed on it - a process called plasticity. It has been shown that one-third of skeletal muscle in an immobilized limb can disappear within weeks. It is as if skeletal muscle recognizes that it is not needed and "remodels" itself into weak muscle. In order for skeletal muscle to exhibit plasticity, specific genes in the muscle sense the change in its usage and respond by altering the quantities of proteins that they produce. Figure 12g shows the benefits of exercise to the various part of the body.

Figure 12g Exercise Benefits [view large image]

Figure 12h shows the types of gene expression triggered by exercise. They can be broadly divided into three categories based on the duration of their activity and on the change in concentration of the mRNA proteins they encode. "Stress response" genes are those that are activated quickly during the later phases of exercise, when their mRNA protein concentrations rise to hight levels, which drop back to normal soon after exercise ends. "Metabolic priority" genes can also be expressed at quite high levels, usually peaking a few hours after the end of the exercise bout but generally returning to pre-exercise levels within 24 hours. These genes assis with specific metabolic stresses, such as coping with low blood glucose. "Metabolic/mitochondrial enzyme" genes produce much lower concentrations of mRNA

Figure 12h Exercise and Gene Expression

proteins, but the levels persist for considerable lengths of time - some have half-lives as long as a week (green). This last category of genes plays a role in muscle plasticity - the increase in mitochondrial and capillary concentrations that comes with fitness.

Meditation - Meditation has been practiced in the East for thousand years and emerges in Western culture lately in various forms. If the mystical layers are removed from its traditional package, the net effect becomes very useful for reducing stress. The switch from "fight and flight" mode to maintenance mode would enhance greatly the health of everyone especially the elderly. It is known that most cells in the body store a large portion of the glucose and other nutrients in the form of glycogen or fat to serve as reserves for future energy demands. However, cells in the brain act differently. They burn up nearly all the fuel almost the moment it arrives. Such process

		requires a constant, uninterrupted flow of oxygen, and few if any of the nutrients are stored for future use. Thus, brain cells are always living on the edge, and never relax. The benefit of meditation is to allow the brain a moment of rest. During meditation the brain would have a chance to repair damages to the cells and to flush out waste from within the cells. Other beneficial effects include the improvement of the immune system for fending off diseases. Figure 13a and 13b show a standing and a sitting posture for the "simplified" meditation. It is not important whether the practitioner is standing, sitting or lying down. The most important requirement is to relax both the mind and the body. Initially it may be necessary to find a quiet place to minimize distraction. Eventually the mind learns to detach from the noise and other external stimuli. The effect also shows up in daily life. For example, there would be more tolerant toward alien beliefs, obnoxious behaviors, and other unpleasant happenings; it would also improve mental alertness and physical fitness.
Figure 13a Meditation, Standing	Figure 13b Meditation, Sitting	See "common meditation methods" as appeared in the January 8-14, 2011 issue of "NewScientist"; also an update on meditation.

The 2019 article "Neural Excitation Moderates Lifespan" in Nature reveals a scientific finding which links the nervous system with ageing. It is found that overall neuronal excitation is a major determinant of lifespan, and that it is higher in short-lived individuals and lower in the long-lived. The effect involves many macro-molecules such as IGF1 in controlling growth, REST in reducing neural excitation, and FOXO1 in energy homeostasis, i.e., . The tests were conducted with C. elegans (worms), mice, and human (brain tissue from dead body). The benefit of silence has been known for more than thousand years by Zen practitioners. Figure 14a shows some images and sayings by a monk in Tang Dynasty (822-908 AD). Translation into English would not work very well. However, a casual look at the pictures could invoke a sense of serenity

Figure 14a Zen Wisdom [view large image]

- in the upper couplet, such feeling could be derived from the unperturbed soil on the trail and the stationary water in the pond regardless of the reflective intrusions, while the lower couplet reinforce the same steady feeling of serenity even when something appears to be moving in the surroundings.

Friendly Microbes - It is known that microbes are living in our body from cradle to grave (actually before birth and after death, see "Bacteria in Human"). By 21st Century, it is further realized that friendly microbes in the gut are vital to extend a person's longevity.

Here's some of the bacterial benefits for living in old age :

• Friendly gut microbes improve brain functions and mood.
• They help to get rid of bad microbes. Unfortunately depending on individual, some probiotics can also kill the native microbes, that come with the birth event, disrupting the toilet routine.

	Gut flora play key roles in the functioning and regulation of the immune system, e.g., to prevent over-reacting inflammation. Intestinal bacteria also provide source of energy, nutrients, vitamin B and K. Diverse gut microbiota is associated with healthy ageing.
Figure 14b Rejuvenation of Gut Microbes [view large image]	Figure 14b shows the ways to rejuvenate the gut microbes.

See original article "Secrets of a long and healthy life reside in your gut microbiome", NewScientist 2021 for details.

According to a news report in 2007, the "fountain of youth" is not on the Florida coast as believed by the 16th century Spanish explorer Ponce de León (Figure 09), the hotspots for longevity are (see Figure 15) :

Nicoyan Peninsula in Costa Rica - Men in Nicoya live to age 100 four times as often as men in the United States — even though their medical care costs only about 7 % as much. Sardinia - In this mountainous Italian island of Sardinia, farmers work hard in the fields, drink red wine, eat fruits and vegetables they grew themselves, and are taught to respect their elders. Okinawa - There is no word for "retirement" on this island. Men there have a fifth as much cancer as Americans, and a quarter as much heart disease. Loma Linda in California - It is about an hour's drive east of Los Angeles. Why should one city stand out amid the sprawl of Southern California? Perhaps, said researchers, because the Seventh Day Adventist Church there gives people a powerful sense of community.

Figure 15 Longevity Hotspots [view large image]

Many of the things people do in those widely dispersed places probably sound familiar. People there are active throughout their lives. They eat a lot of fruits and vegetables, but little meat. They don't get fat. They drink a glass or two of red wine a day. They put a premium on family, friends and religion to give them emotional support. Genetics also clearly play a significant role in longevity. The few surprises found in these places include: high altitude and thinner air (which lowers one's blood pressure, and more exposure to the sun means more vitamin D), while eating nuts seems to enable people to live two or three years more than average.

The HelpAge International (with expenditure from charitable activities) has compiled a "Global AgeWatch Index" to rank countries

		according to the social and economic wellbeing of older people (see table below for the criterions in computing the index). Figure 16 ranks 96 countries according to the wellbeing of elderly citizens. While countries in Western Europe and North America rank high in this 2014 survey, Figure 17 shows that these same countries grow old fastest in the next few decades. See the abovementioned links for detailed information down to the level of individual country.
Figure 16 Global AgeWatch Ranking [view large image]	Figure 17 Ageing Population

	Global AgeWatch Index domains and indicators [view large image]

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