Aging

What is Aging?

The processes and inevitability of aging are as certain as death and paying taxes. In the past 5 years, the population of the world has grown by approximately 1.7% per year. On the other hand, the number of elderly people has increased by 2.7% per year. In the developing world, the number of people older than age 65 years will increase by 200% to 400% in the next 30 years. By 2030, 70 million people will be older than the age of 65 in the United States, and, by 2050, 22% of the U.S. population will be considered elderly.

It is generally agreed that with increasing longevity and health, especially in the developed world, the enlarging graying population will create a significant imbalance in health and welfare provision while, at the same time, the younger, wealth-creating proportion of the population will carry an unsustainable burden to support them. Traditional views about retirement age, the naïve view that older people have reduced expectations about the duration and quality of their lives, and the need for older people to contribute to the gross domestic product are being realized slowly. Already, retirement ages are being moved upward in those countries where they still apply.

Age-related chronic diseases may be expected to increase, especially those with major health care provision needs such as cerebrovascular and cardiovascular diseases, dementia, malignancy, osteoarthritis, and degenerative disk disease. Perhaps more important, the healthy but aging population will demand as full and a rewarding standard of health as can be achieved. The understanding, arrest, or even reversal of the processes of aging will become a major research issue in the expectation that a healthy, long-living older population cannot only expect a fulfilled life but also, in exchange, contribute to the wealth of society as a whole.

It may be time also to revise an important benchmark in medicine. When studying the effect of age on the musculoskeletal system, an important consideration arises. That is, what is normal? For example, currently, bone density and the diagnosis of osteoporosis are made in comparison to peak bone mass in the young, mature skeleton. Is this reasonable? Can what is seen as normal for a 25-year-old person really apply to an 80-year-old person? That we grow old and our skeletons continue to remold and adapt is obvious. That the processes involved alter with time is irrefutable. Archaeologists and anthropologists have long used these molding changes to assess the probable age of their clients in funerary and other collections. Therefore, thickening of the skull vault, progressive closure of the cranial sutures, deepening of dural venous indentations, and roughening of the articular surfaces of the symphysis pubis are but a few of the signs that are relied upon. Perhaps, rather than consider the majority of older people to be abnormal by young adult standards, it would be more rewarding to ask: Why have some older people been able to maintain the standards of youth in their old age?

Mechanisms of Aging

The means by which the human animal grows old are unclear. Obviously, environmental issues are important. A life spent in a coal mine or a childhood without adequate nutrition will inevitably prejudice against a long and healthy life span. A number of complex cellular processes are working also toward entropy. One such may be telomere length. Telomeres are repeated sequences of five bases that preserve the integrity of genes during DNA replication. Their function has been likened to preventing the DNA strands from unraveling. The telomere chain length varies in individuals at birth, but, every time a cell replicates, daughter cells have shorter chains until they are spent. Older people with shorter telomeres are eight times more likely to die from an infectious disease and three times more likely to have a heart attack. On the other hand, it has been suggested that deficient telomere chains may be beneficial by inhibiting further cell replication and thereby be a means of inhibiting malignant transformation. It also has been suggested that an inverse relationship may exist between life span and the number of children borne to an individual.

Widespread endocrine changes occur also in the older human. These include the menopause in women, androgen deficiency in men, subsequent loss of skeletal mass of about 1% per year when older than the age of 50 years, decreased concentration of serum growth hormone, and increased incidence of type 2 diabetes. For example, growth hormone loss is associated with reduced gonadal steroids in serum, increasing body fat, reduced muscle mass, and decreasing bone mass. The inherent substantial physiologic organ reserve of youth becomes lost, together with the impact of increasing other pathologic processes. These include the problems of frailty, vascular disease, and loss of cognitive function.

A third area of recent interest is the understanding of age-related changes in mitochondrial function. The essential function of mitochondria is to burn sugars to produce intracellular energy. However, errors or interruptions in this process can result in the production of excess quantities of highly reactive free radicals that damage both mitochondrial and nuclear DNA. Mitochondrial DNA has 13 genes but lacks the crucial ability of nuclear DNA to repair genome damage, such as that associated with cell replication. Furthermore, as mitochondrial DNA is replaced more frequently than nuclear DNA, uncorrected mutations may contribute to the aging process. Research in a mouse model has shown that animals whose ability has been impaired to proofread accurately copies of mitochondrial DNA show reduced life span and premature onset of aging-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis, osteoporosis, anemia, reduced fertility, and heart enlargement.

Whatever processes are involved, it is clear that a familial or genetic tendency occurs with some disorders that are age-related. For example, osteoarthritis is known to have strong linkages in first-degree female relatives, and data from population studies have suggested that progression of osteoarthritis in probands is strongly associated with progression in their siblings. Similarly, hyaline cartilage defects in the knee have a genetic component related to symptomatic knee pain and bone size.

The Aging Musculoskeletal System

The individual components of the skeleton are each associated with specific age-related changes, some of which overlap. For convenience, each component will be considered separately. However, the concept that a joint is a whole organ within a whole patient must never be forgotten. Therefore, a stumbling old man who fractures his hip is more than just an osteoporotic individual. His variable, weak gait may correlate with depression scores rather than his age, gender, muscle strength, or neurologic features, except in terms of frontal lobe and extrapyramidal function. His cautious gait equates to loss of higher cerebral function. In other words, gait changes in older adults, who may walk in fear of falling, may be an appropriate response to unsteadiness and are likely to be a marker of an underlying cerebral pathologic process and not simply a physiologic or psychological consequence of normal aging.