Geriatic nsg

Stochastic Theories regarding Aging

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Error Catastrophe Theory

This theory proposes that over time an accumulation of errors in protein synthesis results in
impaired cellular function. No biologic process is 100% accurate, and errors in transcription
and translation could lead to protein abnormalities. However, most research indicates that
transcription and translation continue to function well with advancing age; if this theory were
correct, aging would occur at an unchanged pace from birth. Other findings that do not
support this theory include evidence that there is (1) no change in amino acid sequence in
proteins from young and old animals, (2) no increase in defective tRNAs with age, and (3) no
age-related differences in the accuracy of poly(U)-directed protein synthesis. In fact, most
alterations of protein found with aging are posttranslational.
Cross-Linking Theory

This theory proposes that the cross-linking of proteins and other cellular macromolecules
leads to age-dependent diseases and disorders. Although this theory cannot explain all the
changes associated with aging, it may account for some. Extracellular collagen becomes
increasingly cross-linked in humans and animals. Although this cross-linking decreases
mobility of certain tissues, it does not appear to have a major clinical impact. However, the
cross-linking of glycosylated proteins may play an important role in age-dependent
opacification in crystalline lens protein and eventual cataract development. Cross-linking
between glycosylated immunoglobulins and glomerular basement membrane proteins and
between glycosylated lipoproteins and arterial wall proteins has also been proposed as
important in the development of age-dependent glomerular and arterial diseases in humans
and in animals.
Wear and Tear Theory

This theory proposes that the cumulative damage to vital irreplaceable body parts leads to the
death of cells, tissues, organs, and finally the organism. For example, DNA is constantly
damaged throughout life, and recent studies indicate the loss of DNA at the ends of
chromosomes (telomeres) in certain organisms with aging. If DNA repair is incomplete or
age-related impairments in repair mechanisms occur, cellular function might progressively
decline. In fact, DNA repair capacity positively correlates with species life span, suggesting a
role of efficient DNA repair in the evolution of longevity. However, studies of DNA repair
during the aging of experimental animals do not show a consistent decline with aging. (Some
studies show a decline; others show no change.) Such studies are complicated by multiple
DNA repair mechanisms and uncertainty about which mechanisms are most critical to aging.
Further refinement of the techniques for detecting DNA damage may help clarify whether it
does accumulate with aging.
Free Radical Theory
Free radicals are highly reactive molecules that can damage membrane proteins, enzymes,
and DNA. The most important source of free radicals is oxygen metabolism, which yields the
superoxide radical O2¯. Proponents of this theory believe that low-level free-radical damage
accumulates over time, resulting in the findings associated with aging. Studies in which
various antioxidants were fed to animals found an increase in life expectancy, but in many of
these studies antioxidant administration was accompanied by weight loss–a potential
confounder because it independently produces a significant increase in life expectancy.
However, levels of the naturally occurring cellular antioxidant superoxide dismutase correlate
well with life span in primates, supporting this theory. Finally, in some lower forms of life,
mutations leading to defects in the production of free-radical-quenching enzymes are also
associated with shorter life span.

Nonstochastic Theories on Aging

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Pacemaker Theories

Certain organs or organ systems (eg, the immune and neuroendocrine systems, notably the
hypothalamus) are thought to be intrinsic pacemakers of the aging process, genetically
programmed to involute at specific times during an organism’s life span. This programmed
senescence is hypothesized to affect the aging of the entire organism.

With aging, both B- and T-cell functions decline, controlled largely by the major
histocompatibility complex (MHC). T-cell functions are more impaired, the decline
paralleling the involution of the thymus gland, which begins in adolescence. In studies of
mice that are identical except for MHC, B- and T-cell functions closely correlate with life
span. Also, the age-related increase in malignancies may be related to the age-dependent
decline in cellular immune surveillance.

As another example, adrenergic activity increases with age and beta-mediated vasodilation
decreases. These changes may be linked to age-related increases in blood pressure, impaired
carbohydrate tolerance, and altered sleep patterns.

Studies of hypophysectomized animals receiving hormone replacement therapy suggested

that aging was slowed and prompted a search for a death hormone, whose level increases
with age, or a Methuselah hormone, whose level decreases with age. However, no data
support these notions.

All of these theories fail to explain the origin of the changes in the pacemaker system itself.
Also, they fail to take into account that not all organisms have well-developed immune or
neuroendocrine systems.
Genetic Theories

Genetic factors are important determinants of aging, although most mechanisms involved are
unknown. Life span is remarkably specific for each species, yet even within species genetic
factors are important. In humans, the life expectancy of identical twins is more similar than
that of siblings, and some families demonstrate a strong predisposition for longevity. Mutant
varieties of Caenorhabditis elegans, a nematode, have been produced with life spans
increased by 50%; the increase appears to result from a single gene in some strains.
Researchers are now attempting to clone and examine this gerontogene.
Variability

Some biologic changes in the elderly are related to aging alone, while others result from
disease. In evaluating and managing health and disease in the elderly, it is important,
although not always possible, to understand and recognize the difference.

The rate of age-related decline in organ function varies greatly; thus, people become less
alike as they age. Also, within any individual, the functions of different organs decline at
different rates, so that kidney function may decline more quickly than heart or lung function.

Age-adjusted criteria have been established for several clinically important functions; eg,
spirometric measures are commonly expressed as “percent of expected” for age and body
size, and cardiac exercise tolerance tests use age-adjusted criteria for maximum heart rate.
With aging, glomerular filtration rate (GFR) declines, and creatinine clearance falls about 10
mL/min for each decade. Because endogenous creatinine production also falls, however,
normal serum creatinine levels remain unchanged. Thus, in the elderly, serum creatinine
levels reflect a substantially lower GFR. Understanding these changes is important in
prescribing drugs for the elderly. However, these are average changes for age, and the
variability in function makes applying averages to each individual difficult.