Mechanisms of Aging: Introduction

Microaccidents include various types of random events that can cause damage to vital structures in the body at the microscopic level. For instance, free radicals, which are highly reactive by-products of normal cellular respiration, can randomly damage key molecules of life, such as DNA, proteins and lipids. Cell membranes are especially susceptible to free radical attack because they are rich in unsaturated fatty acids, which are highly reactive. Mutagens, the chemicals that have the capacity to react with DNA and alter its genetic content, can knock out or disturb the function of genes. Some chemicals, such as aldehydes, can cross-link (tie together) cellular components, reducing their mobility and functional capacity. Although some offenders that produce molecular damage come from environment (e.g. ultraviolet radiation or toxins) and can be avoided, many of the damaging agents are inherent in normal metabolism.

Potentially harmful molecular accidents occur in our cells all the time. The vast majority, however, cause no harm because the damage is quickly fixed by reparation enzymes. Unfortunately, a small percentage of lesions is missed by the repair systems and remains for good. As unrepaired lesions accumulate, they begin to interfere with vital cellular functions. With age, the accumulation of unrepaired damage accelerates, partly because repair mechanisms themselves get damaged and lose efficiency.

Aging clocks

In the early years of aging research, there was a heated debate about the existence of aging clocks. Indeed, single cell organisms and some primitive species obviously do not have them. On the other hand, there is now much evidence that complex organisms, such as mammals, have not one but several types of aging clocks. Firstly, most normal cells in higher organisms have a "clock" in the sense that they can undergo only a finite number of divisions -- as opposed to bacteria, which can potentially grow forever. Secondly, there seems to be a "central clock," located in the brain, which paces both the development and aging of the organism. There are other types of aging clocks, such as the clock shutting down reproductive function in women (menopause), although they seem to be at least somewhat dependent on the pace of central and cellular clocks.

Biological clocks, especially the ones that affect aging, are very different from regular clocks. Their pace can vary varies markedly among individuals, and even more so among species. Different environmental factors or events can make these clocks go faster or slower. For example, stress, excessive food intake and possibly certain nutrient deficiencies speed up aging clocks. Improved stress resistance and possibly therapies that revitalize certain brain structures, particularly hypothalamus and pituitary, slow down these clocks. In rodents, severe caloric restriction started before sexual maturation, causes up to a two-fold increase in life span by, among other things, slowing down some of the aging clocks. Unfortunately, this spectacularly effective method cannot be used in primates in whom severe caloric restriction initiated early in life causes brain damage. On the other hand, even modest limitation of food intake in adults seems to have some anti-aging benefits. Statistical population studies indicate that maintaining a close to ideal weight is optimal for longevity in humans.

Specific Mechanisms of Aging

If you are interested in a comprehansive anti-aging stretegy, you need to learn about specific mechanisms of aging. Here's the articles that address each key mechanism of aging and its practical implications in detail.

Free radicals
DNA damage and repair
Cellular clock
Central aging clock
Glycation and cross-linking
Mitochondrial burnout
Inflammation
Accumulation of wastes
Accumulation of senescent cells
Gene deregulation