BIOCHEMISTRY OF AGING BY MAMUDU VINCENT

Aging is a natural phnomenon. As the average life-span is increasing in developing

countries, the percentage of aged persons in the population is also increasing. In India,
7% of the population are above 60 years. The medical branch dealing with age-related
diseases, is called Geriatrics or Gerentology. All the physiological processes decline as
age advances. However, differences are observed in individuals, with regard to the
disease progression, or how much physical and mental functions are deteriorated.
These may be due to differences in lifestyle, diet, diseases and genetics. Onset of
ageing is earlier in persons with hyperglycemia, hyperlipidemia and hypertension.
Obesity and lack of exercise are other factors which hasten the aging process.
Numerous theories have Chapter been proposed to explain the causes of aging. The
simplest theory is that aging is governed by an organism’s genetic inheritance or
“Genetic clock”. Organisms may have “aging genes” that control the rate of aging and
thus life-span.

1. Cellular theories of aging

Hayflick found that cultured human fibroblasts double only a limited number of times
before they deteriorate, become senescent (aged), lose their capacity to divide and
finally die. The number of cell divisions of cultured cell is roughly related to (a) the age
of the cell donors and (b) the longevity of the species. For example, fibroblasts from the
human embryos, when sustained in tissue culture, divide about 50 times before they
die. Those taken from person after birth divide only 20 to 30 times. Many theories have
been proposed for explaining why cells become incapable of divisions.
a. Mutation or “error” theory: Most biologists of gerontology, believe that as a person
grows older, his genetic material (DNA) gradually becomes impaired. This deterioration
may in some cases be caused by accumulated errors in the replication of DNA. Thus,
mutation may cause aging.
b. “Error catastrophe” theory: According to this theory accumulation of errors in the
amino acid sequence in proteins, specially errors that affect the specificity of enzymes
needed for protein synthesis, will result in further mistakes in protein synthesis and
consequently will lead to cell deterioration and death. These errors may not be the
result of blind chance but may be purposefully programmed by the “aging genes”.
c. Free radical reaction theory: It is proposed that certain free radicals generate
oxidative reactions which can lead to the deterioration of lipids, collagen elastin and
other body substance and may cause aging
.
2. Pacemaker theories of aging
Ageing is caused in part by progressive breakdown in the immunological system. At
present, evidence strongly indicates that the age-related decline in the immunological
functions. This is mainly due to the decrease in activity of the T cells. The body can also
produce antibodies called auto-antibodies that attack not only foreign substances but
also to the natural proteins of the body. These auto-antibodies are speculated to cause
age-associated diseases such as rheumatoid arthritis, systemic lupus erythematosus,
etc. As age advances, immunological system becomes less able to distinguish “self”

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from “non-self” and as a result, proceeds to destroy normal and desirable proteins of the
body.
3. Chalones
In normal tissues of the full-grown mammals an equilibrium state is reached between
mitosis and cell death. Such inhibition of cell division is apparently the result of
products of the tissues themselves. These tissue-specific inhibitors of mitosis are
collectively called chalones. Each tissue produces 2 types of chalones, one of low
molecular weight (about 1000 to 3000) and another of high molecular weight (about
30,000 to 50,000). When cells in tissue culture are freed of chalones by washing they
resume mitosis and proliferation. Chalones presumably attach to specific receptor sites
on cell membranes and exert their inhibitory effects. In summary, the major contributory
factors of aging process are: (a) Reactive oxygen species; (b) Cellular senescence; (c)
Apoptosis or programmed cell death; (d) Somatic mutations in cellular and
mitochondrial DNA.

4. Telomerase
Another molecular cause for senescence is the declining activity of telomerase (Fig.
40.19). Telomerases are essential for stabilizing the chromosomes. As age of the cell
progresses, telomerase activity progressively decreases. So there is sequential
shortening of the length of the DNA at each division. This leads to eventual cell death.
Malignancy leads to continuous expression of telomerase, with consequent immortality
of cancer cells.

5. Mutations in mitochondrial DNA

Mitochondrial DNA is more exposed and susceptible to damage by free radicals
(reactive oxygen species). Such damages when accumulated, lead to reduction of
oxidative phosphorylation. The exposure to oxidative stress leads to irreparable
damage, and final destruction of the cell.

6. Heat shock proteins (HSP)

They are products of highly conserved genes. HSPs protect the cell against a variety of
stresses such as, heat, heavy metals, drugs and toxins. The HSPs will mediate the
disposal of damaged proteins and guide towards the correct folding into exact three-
dimensional structure (Chapter 41). The HSP response is reduced in senescent cells
and in older individuals.

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