The term ‘aging‘ (or more correctly ‘senescence’) refers to post-maturational processes leading to diminished homeostasis and increased vulnerability of the organism. The worldwide prolongation of the mean life expectancy as well as the drastic reduction of fertility rate result in a rapid increase of the size of the elderly population (over the age 65), both in numbers and as a proportion of the whole.

In consequence, increasing number of people in advanced age raises many social and economic problems because these beneficiaries of health and pension funds are supported by a relatively smaller number of potential contributors (i.e.  those in the economically active age of 18 – 65), and results also in an increase of the number of people suffering from age-related diseases (such as atherosclerosis, neoplastic disease, neurodegenerative diseases). Therefore, there is a search for any therapeutic agent improving quality of life of the elderly. A role for melatonin as such a compound was recently suggested.

Melatonin which is currently available in some countries (e.g. USA, Argentina, and Poland) as a food supplement or over-the-counter drug, is often advertised as a “rejuvenating” agent. Although many theories relating melatonin to aging have been put forward, the role of this compound in the aging processes is not clear. However, there are several reasons to postulate a role for melatonin in aging:

– melatonin participates in many vital life processes and its secretion falls gradually over the life-span;

– melatonin is a potent free radical scavenger, and the proposed link between oxidative stress and aging itself as well as age-related diseases suggest a role for melatonin in these processes;

– reduced concentrations of melatonin in the elderly may be related to lowered sleep efficacy very often associated with advanced age;

– reduced concentrations of melatonin may be related to deterioration of many circadian rhythms very often associated with advanced age.

– melatonin exhibits immunomodulatory properties, and a remodeling of immune system function is an integral part of aging.

Melatonin and free radicals

Free radicals are reactive molecules which have an unpaired electron and are continuously produced in cells as byproducts of oxidative phosphorylation and fatty acid oxidation. It should be stressed that the free radical theory of aging formulated initially by Harman seems to be recently one of the most compelling explanations for many degenerative changes associated with aging. According to the free radical theory of aging the deterioration of functions in the advanced age is in part related to the damage of subcellular constituents, cells, and organs sustained as a consequence of their persistent bombardment by free radicals.

This damage is a result of disturbance in the prooxidant-antioxidant balance in the organism. Moreover, free radicals are believed to be involved in pathogenesis of large variety of diseases, including age-related diseases (such as Alzheimer’s disease, Parkinson’s disease, neoplastic disease, atherosclerosis, cataract, etc.).

It has been discovered that melatonin is involved in antioxidative defense system of the organism, designed to protect molecules from damage by toxic oxygen radicals. Melatonin is a potent free radical scavenger and antioxidant. It scavenges both hydroxyl radicals and peroxyl radicals, although it is a more efficient direct scavenger of the highly toxic hydroxyl radicals. Additionally, melatonin stimulates a number of antioxidative enzymes, e.g. glutathione peroxidase and glutathione reductase.

Melatonin is both lipophylic and hydrophilic and diffuses widely into cellular compartments, thus providing on-site protection against free radical mediated damage to biomolecules. It may carry out its antioxidant function with equal efficiency in multiple cellular compartments, i.e. in the nucleus, cytosol, and membranes. It should be stressed that melatonin is the only antioxidant known to decrease substantially after middle age, and this decrease closely correlates with a decrease in total antioxidant capacity of human serum with age.

Melatonin and sleep in advanced age

It is well known that increased frequency of sleep disorders occurs in the advanced age . Sleep disturbances affect 40 to 70% of elderly population, including 10 – 25% of the elderly complaining of persistent insomnia. This may influence the subjective and objective general physical health of the elderly, and may be associated with mental health problems including poor life satisfaction or quality of life as well as poor cognitive, psychological, and social functioning (24). On the contrary, as indicated above, melatonin concentrations significantly decrease in the elderly.

According to Cajochen et al. (2003) the soporific and chronobiotic properties of  melatonin make it an optimal candidate for treating sleep. There are numerous studies in which melatonin was administered in elderly patients suffering from sleep disorders. Although majority of data show that melatonin improved sleep parameters in the elderly, in some studies sleep was unaffected by melatonin.

Melatonin was shown to significantly improve subjective and/or objective sleep parameters (reduces sleep latency and/or increases sleep efficacy and total sleep time) in some individuals. Lavie et al.suggest that from the accumulated data it is evident that melatonin characteristics are not those of a typical hypnotic or sedative. Melatonin affects sleep in much more subtle way. The authors propose that the role of melatonin in the induction of sleep does not involve the active induction of sleep, but rather is mediated by an inhibition of a wakefulness-producing mechanism. Although melatonin can not be considered as universally effective drug for treatment of sleep disorders, it may be helpful in elderly patients suffering from insomnia.

Melatonin and immune system in the elderly

Many alterations in the immune system are observed in the individuals in advanced age, generally viewed as a deterioration of immunity, and termed ‘immunosenescence’ which have clear clinical consequences, leading to increased incidence of infections, cancers, autoimmune disorders, and chronic inflammatory diseases. The age-associated decline in the immune system refers to both humoral and cellular responses, although an overwhelming decrease in T cell functions with aging seems to play the main role.

Is there a rationale for Melatonin supplementation in the elderly?

It has been proposed that melatonin may be of some therapeutic significance, and in some countries it is available as OTC drug or even food supplement. In Poland melatonin is registered since 2000 as OTC drug for sleep and circadian rhythm disorders. Beside widely accepted indications for therapeutic use of melatonin (i.e. sleep disorders and such circadian clock disturbances as jet-lag and phase-shifting of the circadian clock in blind people), there are also perspectives for its broader use, although other possibilities for therapeutic usefulness of melatonin are not definitively proved.

Melatonin is often advertised as an antiaging agent (“fountain of youth”). However, presently available data do not allow us to conclude that melatonin may have a role in extending normal longevity. Although melatonin can not be recognized as a rejuvenating” agent, some of its actions may be beneficial for the process of aging.

Administration of melatonin may improve temporal organization in advanced age. Moreover, it has beneficial effects on sleep as well as on age-related diseases.  Although recommendations of melatonin supplementation in elderly should be considered, there is a need for extensive studies on the use of melatonin in order to improve the quality of life in advanced age. It should be stressed that melatonin treatment seems to be safe because of its remarkable low toxicity and absence of any significant side effects. Additionally, melatonin has been shown to reduce the toxicity and increase the efficacy of a large number of drugs whose side effects are well documented.