Page 28 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Aging and Life Expectancy
Aging is a normal, inevitable process that ends in the accumulation of harmful somatic DNA
with death. While the mean life expectancy of mutations and in a decreasing telomer length,
a newborn is estimated to have been a mere 10 which limits the ability of the cell to divide.
years 50 000 years ago and ca. 25 years in an- Many inherited diseases and (often polyge-
cient Rome (→ A1), it is nowadays between 38 netically) inherited risk factors, have a second-
(in Sierra Leone) and 80 years (Japan). It is ary effect on life-span, e.g. in favoring the de-
mainly due to decreased infant mortality and velopment of certain tumors. Studies of mono-
the effective treatment of infections (especial- zygotic (uniovular) twins have, however,
ly in children) that life expectancy in the in- shown that at least two thirds of variability of
dustrial nations has increased markedly in the life-span is not genetically determined.
past 100 years (e.g., in the USA from 42 to 72 As one gets older, a reduction of bodily func-
years in men and to 79 in women). As a result, tions (→ C) occurs as, for example, of maxi-
diseases of the elderly are the most common mum breathing capacity, cardiac output (CO),
causes of death: ca. 50% are diseases of the maximal O 2 uptake, and glomerular filtration
cardiovascular system; 25% are tumors.
rate (GFR). Muscle and bone mass decrease,
Fundamentals maximal life-span being reached, which, now while the amount of fat increases, largely due
These are largely diseases that prevent a
to endocrine factors (→ D). For these reasons it
is their frailty that is the limiting factor for
as then, is about 100 years (→ A1). Thus, of
most (otherwise healthy) very old persons.
those aged 98 years, only 10% will still be alive
diminished muscle power, slowed reflexes,
(→ A2). The world record set by the French
1 three years later and after 10 years only 0.005% This weakness of old age is characterized by
woman Jeanne Calment (122 years) is thus an impaired mobility and balance, and reduced
extremely rare exception. stamina. The result is falls, fractures, reduced
The causes of aging are unclear. Even indi- daily physical activity, and loss of indepen-
vidual cultured cells will “age”, i.e., after a cer- dence. Muscle weakness is not only caused by
tain number of cycles they stop dividing (fetal physiological aging processes (→ D) and wear
pulmonary fibroblasts after ca. 60 divisions; and tear (e.g., damage to joints), but also by
→ B). Only a few cells are “immortal” (unlim- lack of movement, leading to a vicious circle.
ited proliferation, e.g., germinal, tumor, and Purely age-related problems with memory
hemopoietic stem cells). Life-span and age are (especially problems of orientation in an unac-
in part genetically determined. Thus, mutation customed environment) seem to be caused by
of the gene age-1 of the nematode can double a disturbed long-term potentiation in the cor-
its life-span, and the human gene that codes tex and hippocampus (reduced density of glu-
for DNA-helicase can cause premature aging tamate receptors, type NMDA, in the dentate
(progeria of the adult = Werner’s syndrome). gyrus). It is now doubted whether a significant
Recently a gene (MORF4) was discovered loss of neurons, such as occurs in Alzheimer’s
whose exclusion by mutation makes cultured disease or atherosclerosis-induced reduction
cells immortal: if the normal MORF4 gene is in cerebral blood flow, is part of the normal
passed to (immortal) cancer cells, it stops their process of aging.
proliferation. In “old” cells, MORF4 is up-regu-
lated; in proliferating cells it is down-regu-
lated. The age-1 mutation produces, among
other effects, an increased resistance against
free radicals. That oxidative damage is impor-
tant for aging, is also suggested by the fact that
membrane lipids, DNA, and proteins damaged
by O 2 radicals accumulate with age, while at
the same time the activity of enzymes that
18 guard against oxidation is reduced. On the
other hand, defects of the helicase gene result
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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