Aging

Demographics of Aging

The birth rate in the U.S. has been falling and is now about 15/1000. The death rate has also been falling and is now about 9/1000. The overall population growth rate (not counting immigration) is about 0.9%. Compare that with Kenya's 4.3% and Sweden's 0.1%.

Longevity has increased. The life expectancy in the U.S. in 1900 was 47 years. By the 1990's the average lifespan for males reached 72 years and for females 79. Compare that to Japan's life expectancy of 76 years for males and 82 years for females, or Ethiopia's 50 years for males and 53 years for females.

Aging and Health

Aging is NOT a disease, but the changes that occur with aging make aged persons more susceptible to disease. The theoretical maximum lifespan is 120 years and is not increasing. The ideal maximum lifespan is currently about 85 years. Mostly within this century, about 80% of the causes of premature deaths have been eliminated, mostly infectious diseases. Changes in lifestyle, such as diet and exercise, may further decrease or postpone chronic illness. Acute illness (infections) can often be prevented (vaccination) or controlled (antibiotics); surgically amenable diseases such as appendicitis are easily treated. Chronic illnesses (heart disease, cancer, stroke) now account for most deaths in developed nations.

The ideal strategy for improving longevity while maintaining quality of life is to compress the incidence of death into a narrow range in old age. This would give persons a long, healthy life and limit major illness to only a few months or years later in life. Expensive medical treatments do not necessarily increase longevity. Policy makers in the future must determine how best to utilize resources (preventive medicine vs acute care vs chronic care)

Theories of Aging

• Cellular Changes: One theory holds that changes at the cellular level are decisive in the aging process. Cell organelles wear out over time. There is cumulative free radical damage to DNA and to proteins (perhaps due to lack of antioxidants). There is protein degradation through cross-linking of amino acids (same as formaldehyde) and glycosylation (as in cataracts). We can see that cellular "garbage" in the form of intracellular lipochrome collects (as in brown atrophy of the heart) with aging.

• Genetics: Another theory suggests that aging is determined by genetic programming and malfunction. This may be due to a limited number of cellular divisions that can take place. For example, fibroblasts can divide about 50 times, then stop. Other cells may act similarly; the number of divisions is not increased by the time that passes between divisions. There can be errors in DNA replication and repair, with accumulation of mutations or transcription errors. An enzyme called telomerase, which counteracts the tendency of the ends of chromosomes to shorten with each cellular division, may have decreased activity so that the telomeric ends of chromosomes shorten, and the ability of chromosomes to replicate is lost. The process of programmed cell death (apoptosis) may be part of a sequence of cell maturation.

• Loss of Homeostasis: Another theory of aging is based upon the observation that there is loss of "organ reserve" capacity, which is normally 4 to 10 times that needed to sustain life. For example, you can live with just half of one normal kidney. Organ reserve diminishes linearly with time after age 30. There is also loss of cellular "complexity" as evidenced by reduced branching of neuronal dendrites, by less variability of heart rate, and by loss of pulsatile hormonal release. This decreases the body's ability to react quickly to changes in the environment, or keep body functions in tight control. The result is an inability of the body to cope with--or adapt to--stress or changes in the environment, trauma, or disease states, even if minor.

• Environmental Stress: Stress-induced increases in glucocorticoids over time dampen the feedback response of neuronal steroid receptors in the brain, leading to hypersecretion of corticosteroids. Increased corticosteroid production contributes to immune suppression, osteoporosis, and impaired cognition; T lymphocyte function also declines

• Neuroendocrine Dysfunction: Aging may be related to changes in hormonal output. The hypothalamic-pituitary-adrenal axis regulates much of development and involution of the reproductive functions. Production of dehydroepiandroterone (DHEA), growth hormone, and secondary sex steroids decrease with age

• Nutrition: The one sure way to increase the lifespan of laboratory animals (rodents) is to restrict caloric intake. Proposed mechanisms for this phenomenon include: increased free radical production with high caloric intake and decreased mutation rate with decreased caloric intake

Progeria

Progeria is a disease model of aging. This very rare disease is seen in children. The morphologic features of aging are manifested in early childhood. The etiology for this disorder is unclear

Organ System Function in Aging

The decreases in organ function observed as persons age could be due to any or all of the following:

• Physiologic deterioration

• Disease processes (something to be prevented or treated by a health care worker)

• Environment (pollution, trauma, sun exposure)

• Lifestyle (diet, drug use, work habits) changes that an individual can make

Below are discussed findings in organ systems in aging. It is often difficult to separate disease processes more likely to be seen in older persons from changes that are strictly age-related.

Central Nervous System

Brain function diminishes with aging. There is a gradual loss of neurons in the cerebral cortex. Neurons cannot divide and cannot be replaced. There can be cumulative effects of cardiovascular and cerebrovascular disease. "Strokes" can be due to infarction or hemorrhage. Infarction can occur with thromboemboli, usually from a diseased heart, or from cerebral arterial atherosclerosis. Hemorrhages most typically occur with vascular changes from hypertension.

Past the age of 50 to 60, there is an increased risk for development of Alzheimer's disease (AD). AD is the most common cause for dementia. This disease is due to unknown factors, but the end result is well-described: increased cortical senile plaques and neurofibrillary tangles along with neuronal loss and gliosis.

Eye

The crystalline lens of the eye becomes less distensible with aging. This decreases the ability of the eye to accomodate vision for near objects. The process is called presbyopia, and it typically becomes noticed when persons reach their 40's. The "cure" is the wearing of glasses with lenses for close focusing--bifocals or trifocals.

Older persons are more likely to develop opacification of the crystalline lens known as a cataract. Such opacification leads to decreased visual acuity.

Ear

With aging comes some degree of hearing loss. This is termed presbycusis. The etiologies include:

• Loss of cochlear structure: the delicate hair cells can be damaged from exposure to loud noises. The ability to hear high-pitched sounds goes first.

• Otosclerosis: the small ossicles fuse together, reducing conduction of sound through bone.

• Nerve dysfunction: the acoustic (8th) nerve may not work as well.

Cardiovascular System

There are physiologic changes that occur with aging. The maximal heart rate and cardiac output decrease. The compensatory mechanisms to support circulation are delayed or deficient, leading to a greater risk for syncope.

There is greater atherosclerosis with advancing years.

Cardiac valvular calcification is more likely to occur in persons past the age of 50. The mitral valve annulus can become calcified, though this is usually not a cause for heart failure. However, calcification of valvular leaflets, typically involving the aortic valve, can produce valvular stenosis. This is called "senile calcific aortic stenosis".

There can be cardiac amyloid deposition with aging, most often on endocardial surfaces.

Urinary Tract

The glomerular filtration rate (GFR) decreases with aging. However, renal reserve is so great that renal failure is uncommon in aging without the presence of a specific underlying renal disease.

There are more urinary tract infections in elderly women. Women can also experience urinary incontinence with uterine descensus as the ligaments and connective tissues of the pelvis weaken with aging.

Respiratory Tract

Though emphysema is not an aging phenomenon, the environmental insults incurred by the lung over a lifetime lead to mild loss of alveoli, mostly in upper lobes.<.P>

The dusts with carbonaceous pigments breathed in over one's life collect as anthracotic pigment in the lungs and hilar lymph nodes. Anthracotic pigment does not produce significant lung disease.

Musculoskeletal System

The muscle fibers are gradually replaced by fat and fibrous tissue, beginning at age 20, at a rate of about 1% of remaining fibers per year. This explains why athletes in power sports have short careers but why Eddie Hill, a drag racer, can still keep competing over the age of 60. In some sports that combine muscle strength with skill and tactics, athletes may see continued careers and even improved performance into the late 20's or early 30's.

Hyaline cartilage wears out over time, resulting in osteoarthritis and chronic pain, mostly of larger weight-bearing joints first.

Bone mass decreases as one gets older, particularly past age 40 and particularly in postmenopausal women. Building up bone mass with diet and exercise as a child and young adult provides a large reserve against loss. An abnormal, accelerated form of bone loss is called osteoporosis.

Genital Tract

In women, there is a programmed event of aging known as menopause, which typically occurs in the mid-40's. Menopause leads to atrophy of ovaries, uterus, and breasts. The epithelium of the vagina and vulva also become thinner.

In men, there is decreased spermatogenesis with aging, but not necessarily infertility, and it is possible for a very old man to father a child. The incidence of prostatic hyperplasia and carcinoma increase with aging.

Skin

There is loss of skin elasticity with aging, mainly due to thinning of the dermis and loss of elastic tissue fibers (which are not replaced). This produces sagging, wrinkled skin. This process can be accelerated by solar damage from ultraviolet light.

The squamous epithelium of the epidermis becomes thinner and more easily traumatized. This is apparent to anyone who has had experience performing phlebotomy or putting in intravenous access lines in an elderly person.

"Age spots" on the skin of older Caucasians, particularly on the dorsum of the hand, are areas of lentigo senilis. These "senile lentigenes" are usually about 0.5 to 2 cm in size and have light brown pigmentation.

Hematopoietic and Lymphoid Systems

The bone marrow mass decreases with aging. The bulk of hematopoiesis is limited to the ribs, sternum, and vertebrae in the elderly. Though this does not lead to cytopenias in healthy persons, the marrow reserve capacity is reduced when fighting infections or responding to blood loss.

Lymphoid tissues decrease in size with aging, but their functional capacity remains. With infection, it is harder to mount a rapid or large response in an older person. On physical examination, lymph nodes are hard to palpate in adults; thus, any palpable node (particularly a non-tender node) in an adult suggests the possibility of a malignant process.

Major Health Problems in the Elderly

The table below delineates some of the major problems that are likely to be seen in elderly patients:

Neoplasia and Aging

Both incidence and prevalence of cancer increases with age. Over the age of 75 years lung, prostate, breast, and colon cancers become more frequent. This may be related to the accumulation of more mutational "hits" in oncogenes and tumor suppressor genes that render them ineffective.

The table below indicates the cancers that can be seen in older persons:

Problems in Medical Care for the Elderly

• Resistance to infection decreases

• Tolerance to drugs and toxins is diminished, pharmacodynamics altered (partly from diminished renal and hepatic function)

• Healing or recovery from injury or illness is prolonged

• Response to therapy is diminished or prolonged

Prevention of Aging

Choose your parents. The degree of longevity tends to run in families.

Dietary factors have been suggested as one means to increase longevity. Use of antioxidants such as vitamin E or vitamin C has been touted as a means to combat cellular aging and prolong life, but they have yet to be proven effective. This is hard to prove, since so many factors are involved. Special vitamin and mineral supplements (including trace elements such as zinc and selenium) are probably not as important as just an overall good diet.

Continued physical activity is helpful to prolong life and improve the quality of life. Thus, continue to get adequate exercise (use it or lose it).

Maintain mental activity. Persons who remain mentally active, particularly in a social environment, maintain mental function longer.

Choose a good lifestyle. Avoid behaviors that are detrimental to health. Overeating, smoking, and alcoholism are the most common lifestyle choices leading to diseases that increase morbidity and mortality.

Polypharmacy

"Polypharmacy" is the use of multiple drugs and it increases the risk for a greater number of adverse drug reactions and drug interactions, as well as decreased compliance that lessens the effectiveness of the drugs that are taken.

References

Ershler WB, Longo DL. The Biology of Aging. Cancer. 1998;80:1284-1291.

Yancik R. Cancer Burden in the Aged. Cancer. 1998;80:1273-1283.

Flier JS, Underhill LH. Caloric Intake and Aging. N Engl J Med. 1998;337:986-994.