Chapter 1. : Human Aging, Longevity, Death and Life Extension Defined

 Human ageing (sometimes spelled aging) is defined as: "1. The process of becoming older or more mature---4. (gerontology) Becoming senescent; accumulating damage to macromolecules,cells,
tissues and organs with the passage of time." 1.
Two other definitions of human ageing: "Ageing, also spelled aging, is the process of becoming older." 2.
" In humans, ageing represents the accumulation of changes in a human being over time, encompassing physical, psychological, and social change.---Ageing is among the greatest known risk factors for most human diseases; of roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes." 3.
"Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases." 4.

"Longevity" is best thought of as a term for general audiences meaning 'typical length of life' and specific statistical definitions should be clarified when necessary." 5.

Death may be defined as follows:

Long quote

"Death: 1. The end of life. The cessation of life. (These common definitions of death ultimately depend upon the definition of life, upon which there is no consensus.) 2. The permanent cessation of all vital bodily functions. (This definition depends upon the definition of "vital bodily functions.") See: Vital bodily functions. 3. The common law standard for determining death is the cessation of all vital functions, traditionally demonstrated by "an absence of spontaneous respiratory and cardiac functions." 4. The uniform determination of death. The National Conference of Commissioners on Uniform State Laws in 1980 formulated the Uniform Determination of Death Act. It states that: "An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem is dead. A determination of death must be made in accordance with accepted medical standards." This definition was approved by the American Medical Association in 1980 and by the American Bar Association in 1981." 6.

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"Life extension science, also known as anti-aging medicine, indefinite life extension, experimental gerontology, and biomedical gerontology, is the study of slowing down or reversing the processes of aging to extend both the maximum and average lifespan." 7.

"Life expectancy is a statistical measure of the average time an organism is expected to live, based upon the year of their birth, their current age and other demographic factors including sex.The most commonly used measure of life expectancy is at birth (LEB), which can be defined in two ways: while cohort LEB is the mean length of life of an actual birth cohort (al individuals born in a given year) and can be computed only for cohorts born many decades ago, so that all their embers died, period LEB is the mean length of life of a hypothetical cohort assumed to be exposed since birth until death of all their members to the mortality rates observed at a given year." 8.
" Life expectancy differs from maximum life span. Life expectancy is an average that is computed over all people including those who die shortly after birth, those who die in early adulthood in childbirth or in wars, and those who live unimpeded until old age, and lifespan is an individual-specific concept and maximum lifespan is an upper bound rather than an average." 9.
The oldest confirmed recorded age for any human is 122 years (see Jeanne Calment). This is referred to as as the "maximum life span", which is the upper boundary of life, the maximum number of years any human is known to have lived. Theoretical study shows that the maximum life expectancy at birth is limited by the human characteristic value (δ), which is around 104 years." 10.
"In the United States, African-American people have shorter life-expectancies than their European-American counterparts. For example, white Americans born in 2010 are expected to live until age 78.9, but black Americans only until age 75.1. This 3.8 year gap, however, is the lowest is has been since at least 1975. The greatest difference was 7.1 in 1993. In contrast, Asian-American women live the longest of all ethnic groups in the United States, with a life expectancy of 85.8 years. The life expectancy of Hispanic Americans is 81.2 years." 11.
As of 2014, the country with the highest life expectancy is Monaco at 89.52 years;the country with the lowest life expectancy is Chad at just 49.81 years." 12.
The United States ranks number 43 of 224 countries in terms of life expectancy with a 2015 estimate of life expectancy of 79.68. 13.

Normal Age Related Physical Changes and Their Clinical Significance

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"Selected Physiologic Age-Related Changes
Affected Organ or System
Physiologic Change
Clinical Manifestations

Body composition

 
 ↓ Lean body mass
 ↓ Muscle mass
 ↓ Creatinine production
 ↓ Skeletal mass
 ↓ Total body water
 ↑ Percentage adipose tissue (until age 60, then ↓ until death)
 Changes in drug levels (usually ↑)
 ↓ Strength

Increased Tendency towards dehydration

 
Cells

 
 ↑ DNA damage and ↓DNA repair capacity
 ↓ Oxidative capacity
 Accelerated cell senescence
  ↑ Fibrosis
 Lipofuscin accumulation
   ↑ Cancer risk

 

 CNS

 
 ↓ Number of dopamine receptors
 ↑ Alpha-adrenergic responses
 ↑ Muscarinic parasympathetic responses
 Tendency toward parkinsonian symptoms (eg, ↑ muscle tone, ↓ arm swing)

 
  Ears

 
 Loss of high-frequency hearing
 ↓ Ability to recognize speech

 

 Endocrine system

 
 ↑Insulin resistance and glucose intolerance
 ↑ Incidence of diabetes
 Menopause, ↓estrogen and progesterone secretion
 ↓Testosterone secretion
 ↓ Growth hormone secretion
 ↓ Vitamin D absorption and activation
 ↑ Incidence of thyroid abnormalities
 ↑ Bone mineral loss
 ↑ Secretion of ADH in response to osmolar stimuli
 Vaginal dryness, dyspareunia
 ↓ Muscle mass
 ↓Bone mass
 ↑ Fracture risk
 Changes in skin
  Tendency toward water intoxication

 
Q Eyes

 ↓ Lens flexibility
 ↑ Time for pupillary reflexes (constriction, dilation)
 ↑ Incidence of cataracts
 Presbyopia
 ↑ Glare and difficulty adjusting to changes in lighting
 ↓ Visual acuity

 
" GI tract

↓ Splanchnic blood flow
↑ Transit time
 Tendency toward constipation and diarrhea

 
Heart

↓ Intrinsic heart rate and maximal heart rate
  Blunted baroreflex (less increase in heart rate in response to decrease in BP)
↓ Diastolic relaxation
↑ Atrioventricular conduction time
↑ Atrial and ventricular ectopy
Tendency toward syncope
↓ Ejection fraction
↑ Rates of atrial fibrillation
 ↑ Rates of diastolic dysfunction and diastolic heart failure

 
Immune system

 ↓ T-cell function
 ↓ B-cell function
 Increased susceptibility to infections and possibly cancer
 ↓ Antibody response to immunization or infection but ↑autoantibodies

 
Joints

Degeneration of cartilaginous tissues
Fibrosis
↑ Glycosylation and cross-linking of collagen
Loss of tissue elasticity
Tightening of joints
Tendency toward osteoarthritis

 
Kidneys

↓ Renal blood flow
↓ Renal mass
↓ Glomerular filtration
↓ Renal tubular secretion and reabsorption
↓ Ability to excrete a free-water load
Changes in drug levels with ↑ risk of adverse drug effects
Tendency toward dehydration

 
Liver

↓ Hepatic mass
↓ Hepatic blood flow
↓ Activity of CYP 450 enzyme system
 Changes in drug levels

 
Nose

↓ Smell
↓ Taste and consequent ↓ appetite
↑ Likelihood (slightly) of nosebleeds

 
Peripheral nervous system

↓ Baroreflex responses
↓Beta-adrenergic responsiveness and number of receptors
↓ Signal transduction
↓ Muscarinic parasympathetic responses
Preserved alpha-adrenergic responses
Tendency toward syncope
↓ Response to beta-blockers
Exaggerated response to anticholinergic drugs

 
Pulmonary system

↓ Vital capacity
↓ Lung elasticity (compliance)
↑ Residual volume
↓FEV1
↑ V/Q mismatch
↑ Likelihood of shortness of breath during vigorous exercise if people are normally sedentary or if exercise is done at high altitudes
↑ Risk of death due to pneumonia
↑ Risk of serious complications (eg, respiratory failure) for patients with a pulmonary disorder

 
Vasculature

↓ Endothelin-dependent vasodilation
↑ Peripheral resistance
Tendency toward hypertension
↓=decreased; ↑= increased; FEV1= forced expiratory volume in 1 sec; V/Q =ventilation/perfusion."14.

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"Age-Related Physiological Changes and Their Clinical Significance

Abstract

Physiological changes occur with aging in all organ systems. The cardiac output decreases, blood pressure increases and arteriosclerosis develops. The lungs show impaired gas exchange, a decrease in vital capacity and slower expiratory flow rates. The creatinine clearance decreases with age although the serum creatinine level remains relatively constant due to a proportionate age-related decrease in creatinine production. Functional changes, largely related to altered motility patterns, occur in the gastrointestinal system with senescence, and atrophic gastritis and altered hepatic drug metabolism are common in the elderly. Progressive elevation of blood glucose occurs with age on a multifactorial basis and osteoporosis is frequently seen due to a linear decline in bone mass after the fourth decade. The epidermis of the skin atrophies with age and due to changes in collagen and elastin the skin loses its tone and elasticity. Lean body mass declines with age and this is primarily due to loss and atrophy of muscle cells. Degenerative changes occur in many joints and this, combined with the loss of muscle mass, inhibits elderly patients' locomotion. These changes with age have important practical implications for the clinical management of elderly patients: metabolism is altered, changes in response to commonly used drugs make different drug dosages necessary and there is need for rational preventive programs of diet and exercise in an effort to delay or reverse some of these changes." 15.

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Long Quote

" Vital Signs: Normal Ranges for Adults and Elderly

Temperature 36 to 37.5 degrees Celsius
96.8 to 99.5 degrees Fahrenheit

Pulse (Adult) 80 Bpm average (60-100)  range
Pulse (older adult) 70 Bpm average (60-100) range

Respirations (Adult)  16 per minute (12-20) range
Respirations (older Adult) 16 per minute (15-20) range

Blood Pressure: Normal Normal: 120 Systolic / 80 Diastolic (mmHg)
Blood Pressure: Pre-hypertension 120-139 Systolic / 80-89 Diastolic (mmHg)
Blood Pressure: Hypertension (stage 1)n 140-159 Systolic / 90-99 Diastolic (mmHg)
Blood Pressure: Hypertension (stage 2)  >160 Systolic / >100 Diastolic (mmHg)

Hypotension Systolic reading consistently between 85 and 110 (mmHg)

Oxygen Saturation  95-100% (Sp02) less than 70 is life threatening"  16.


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In addition, pulse pressure increases in the elderly with an increased incidence of systolic hypertension, vascular stiffness, and increased pulse pressure.
The following quote provides a succinct summary of the changes associated with aging in the cardiovascular system.

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Conclusions

"Aging leads to a multitude of changes in the cardio-vascular system, and it is a powerful predictor of adverse cardiovascular events. A hallmark of this process is increased central vascular stiffness, which results in an earlier return of the reflected pulse wave, adding to the forward wave and consequently augmenting central systolic blood pressure, widening pulse pressure, increasing cardiac loading conditions, and compromising vital organ perfusion. Although systolic blood pressure and pulse pressure are surrogates for this process, vascular stiffness can be measured more precisely utilizing pulse wave velocity (carotid-femoral)].

Vascular stiffness, an index of vascular health, has been shown to confer additional independent predictive value for adverse cardiovascular outcomes. Vascular stiffness is potentially modifiable if we understand the specific underlying mechanisms. Importantly, even in the absence of targeted therapies, an understanding of these concepts has prognostic implications, a concept already established in cardiology and emerging in the area of perioperative medicine." 17.

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Pulse pressure is the difference between the diastolic and systolic blood pressure.
If the pulse pressure is greater than 60 in the elderly, it is correlated with cardiovascular disease and heart attacks.
Therefore, an elderly individual should carefully monitor not only his or her blood pressure but, also, his or her pulse pressure for signs of cardiovascular disease.
The following quote from a Mayo Clinic publication goes into more detail with regard to the same.

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"Blood pressure readings are given in two numbers. The top number is the maximum pressure your heart exerts while beating (systolic pressure), and the bottom number is the amount of pressure in your arteries between beats (diastolic pressure).
The numeric difference between your systolic and diastolic blood pressure is called your pulse pressure. For example, if your resting blood pressure is 120/80 millimeters of mercury (mm Hg), your pulse pressure is 40.
For adults older than age 60, a pulse pressure greater than 60 can be a useful predictor of heart attacks or other cardiovascular disease; this is especially true for men.
In some cases a low pulse pressure (less than 40) may indicate poor heart function. A higher pulse pressure (greater than 60) may reflect leaky heart valves (valve regurgitation), often due to age-related losses in aortic elasticity.
However, systolic and diastolic pressure should also be considered alongside pulse pressure values. Higher systolic and diastolic pairs imply higher risk than lower pairs with the same pulse pressure: 160/120 millimeters of mercury (mm Hg) indicates a higher risk than 110/70 mm Hg even though the pulse pressure in each pair is 40.
The most important cause of elevated pulse pressure is stiffness of the aorta, the largest artery in the body. The stiffness may be due to high blood pressure or fatty deposits damaging the walls of the arteries, leaving them less elastic (atherosclerosis). The greater your pulse pressure, the stiffer and more damaged the vessels are thought to be.
Other conditions — including severe iron deficiency (anemia) and an overactive thyroid (hyperthyroidism) — can increase pulse pressure as well.
Treating high blood pressure often reduces pulse pressure, although different medications may have varying impacts." 18.

What can an individual do to address the aforementioned vascular stiffness, it's associated widened pulse pressure and associated cardiovascular anomalies?
Generally the following will modulate vascular stiffness and it's associated cardiovascular anomalies as well as increase the chances of an overall healthy aging experience: 1. Monitor and appropriately address blood pressure problems; 2. Monitor and appropriately address blood sugar problems; 3. Adequate sleep; 4; Adequate exercise; 5. Monitor and maintain an appropriate weight;6. Don't smoke; and 7.. Have an adequate and well balanced diet. 8. Have regular check ups with your physician."No matter what your age, you have the power to change many of the variables that influence how long you live, and how active and vital you feel in your later years.

"No matter what your age, you have the power to change many of the variables that influence how long you live, and how active and vital you feel in your later years. Actions you can take to increase your odds of a longer and more satisfying life span are really quite simple:

1. Don't smoke.
2. Enjoy physical and mental activities every day.
3. Eat a healthy diet rich in whole grains, vegetables, and fruits, and substitute healthier monounsaturated and polyunsaturated fats for unhealthy saturated fats and trans fats.
4. Take a daily multivitamin, and be sure to get enough calcium and vitamin D.
5. Maintain a healthy weight and body shape.
6. Challenge your mind. Keep learning and trying new activities.
7. Build a strong social network.
8. Follow preventive care and screening guidelines.
9. Floss, brush, and see a dentist regularly.
10.Ask your doctor if medication can help you control the potential long-term side effects of chronic conditions such as high blood pressure, osteoporosis, or high cholesterol." 19.

The following quote is a more specific answer to how vascular stiffness and it's associated wide pulse pressure and cardiovascular anomalies can be appropriately addressed.

"Many interventions involving lifestyle and dietary modifications, for example, smoking cessation [68], use of unsaturated fatty acids [69], isoflavones (abundant in soy beans) [70], reduced dietary salt intake [71], regular cardiovascular exercise [72], and moderate alcohol consumption [73, 74] have all been linked to reducing vascular stiffness. Other strategies involve pharmacologic interventions like calcium channel blocker, diuretics, ACE inhibitors, beta-blockers, nitrates, phosphodiesterase-5 inhibitors, and statins. Even though all these therapies lower blood pressure, their effect on arterial stiffness is only modest." 20..


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"All the world’s a stage,
And all the men and women merely
 players;
They have their exits and their entrances,
And one man in his time plays many parts,
His acts being seven ages. At first, the
infant,
Mewling and puking in the nurse’s arms.
Then the whining schoolboy, with his
 satchel
And shining morning face, creeping like
 snail
Unwillingly to school. And then the lover,
Sighing like furnace, with a woeful ballad
Made to his mistress’ eyebrow. Then a
soldier,
Full of strange oaths and bearded like the
pard,
Jealous in honor, sudden and quick in
quarrel,Seeking the bubble reputation
Even in the cannon’s mouth. And then the
justice,
In fair round belly with good capon lined,
With eyes severe and beard of formal cut,
Full of wise saws and modern instances;
And so he plays his part. The sixth age
shifts
Into the lean and slippered pantaloon,
With spectacles on nose and pouch on side;
His youthful hose, well saved, a world too
wide
For his shrunk shank, and his big manly
voice,
Turning again toward childish treble, pipes
And whistles in his sound. Last scene of all,
That ends this strange eventful history,
Is second childishness and mere oblivion,
Sans teeth, sans eyes, sans taste, sans everything." 20.