Theory of Aging

1. Genetic Clock Theory

- It has been genetically programmed
- The genetic clock has been rotated according to a replication
- Genetic control of age -> by cellular level
- Nucleus that determines the amount of replication -> then ages and dies
- this clock counts mitosis and stops cell replication
2. Somatic Mutation
- There's been a life-time mistake
- Error in transcription process (DNA -> RNA) or in translation process (RNA -> protein /
enzyme)
3. Damage to the Immune System
- Repetitive mutation due to post-translational protein changes -> the immune system's ability
to decrease
- Autoimmune events occur
- Defense of the immune system is reduced
- All somatic cells undergo an aging process, except for sex cells and cancer cells
4. Free Radical Damage
- It is a reliable theory
- Considered as the leading cause of cell function impairment
- Are damaging, highly reactive -> reacts with DNA, proteins, unsaturated fatty acids, in cell
membranes
5. Due to Metabolism
- Also called "Glycosylation Theory"
- The main role -> protein glycoses where a nonenzymatic glycosylation process that produces
glucose-protein linkage (AGEs)
- As a result -> accumulation occurs in various tissues thus increasing tissue stiffness,
including collagen and reduced elasticity of blood vessels
Theories of Aging
Scientific research provides a number of plausible theories of aging, which can be grouped into
two major categories. Error or damage theories propose that aging occurs because of persistent
threats from damaging agents and an ever-declining ability to respond to or repair this
damage. Program theories postulate that genetic and developmental factors most significantly
determine the biologic life course and the maximal age of the organism. In actuality, biologic
aging may reflect a complex combination of many types of events.

The free radical theory of aging proposes that oxidative metabolism results in an excess of highly
reactive byproducts, called oxygen free radicals, which damage proteins, DNA, and lipids.
Molecular injury eventually leads to cell dysfunction and ultimately to tissue and organ disrepair.
A second theory asserts that the accumulation of glucose-related molecules on proteins
contributes to their dysfunction and degradation. These “glycosylated” molecules become more
abundant over time and lead to impaired function at the tissue and organ level. Theory
proponents point to the many chronic problems that routinely arise in patients with diabetes
mellitus as proof of the significance of this phenomenon.

A different line of reasoning asserts that human lifespan and aging result from genetic-based
timing mechanisms. Older theories suggest that evolutionary pressures are biased for traits that
promote health and reproduction in early adulthood, possibly at the expense of health and
function in late life. Furthermore, little selective pressure exists against negative traits that
emerge in late life, leaving humans prone to the ill effects of aging. Geneticists have identified,
among species of fruit flies and certain nematodes, specific genes that result in a significant
prolongation in the organism's lifespan. Work is ongoing to discover similar genetic sequences
among mammalian models.

Study of the enzyme telomerase has also generated much interest among theorists on aging. In a
process called apoptosis, cells undergo programmed death to be replaced by younger cells. These
divisions and replacements are limited by the number of generations intrinsic to a specific cell
line (the Hayflick phenomenon). As telomeres located on the ends of chromosomes are depleted,
cell aging and demise eventually occur. The enzyme telomerase prevents telomere shortening
and may increase a cell's number of allotted replications and thereby extend the lifespan of the
organism. Of course, this advantage must be weighed against the price of “immortality,” namely
the increased risk of malignancy.

Caloric restriction (CR), or the purposeful reduction of food intake, is the only intervention that
has been shown to reproducibly extend maximal lifespan in certain laboratory animal models. In
rats, lifespan increases an average of 20 months with a 40% reduction in calories. Rhesus
monkeys enrolled in a trial of caloric restriction appear to have improvements in metabolic
markers and a lower disease burden than controls after 15 years but have had no definitive
extension in lifespan. The mechanism is not well understood but may be metabolically mediated.
In observational studies in humans, those with lower average body temperature, lower insulin
levels, and higher dehydroepiandrosterone sulfate (DHEAS) levels (all changes found in
calorically restricted monkeys) appeared to survive longer. Current research is focused on
reproducing this phenomenon in human subjects and discovering chemical agents that mimic or
mediate these metabolic effects, including resveratrol and sirtuins.