A 77-year-old man comes to your office at his wife’s insistence. He has had documented moderate hypertension for 18 years but does not like to take his medications. He says he has no real complaints, but his wife remarks that he has become much more forgetful lately and has almost stopped reading the newspaper and watching television. A Mini-Mental State Examination reveals that he is oriented as to name and place but is unable to give the month or year. He cannot remember the names of his three adult children or three random words (eg, tree, flag, chair) for more than 2 minutes. No cataracts are visible, but he is unable to read standard newsprint without a powerful magnifier. His hearing and comprehension of conversation appear to be limited (he nods and smiles in response to both statements and questions). Why doesn’t he take his antihypertensive medications? What therapeutic measures are available for the treatment of Alzheimer disease? How might macular degeneration be treated?
Society has traditionally classified everyone over 65 as “elderly,” but most authorities consider the field of geriatrics to apply to persons over 75—even though this too is an arbitrary definition. Furthermore, chronologic age is only an indirect determinant of the changes pertinent to drug therapy that occur in older people. In addition to the chronic diseases of adulthood, the elderly have an increased incidence of many conditions, including Alzheimer disease, Parkinson disease, and vascular dementia; stroke; visual impairment, especially cataracts and macular degeneration; atherosclerosis, coronary and peripheral vascular disease, and heart failure; diabetes; arthritis, osteoporosis and fractures; and cancer. Hearing impairment and urinary incontinence are extremely common. As a result, the need for drug treatment is great in this age group. And as the average life span approaches (and in some countries, already exceeds) 80 years, this need will increase dramatically.
When all confounders are accounted for, age itself is still the strongest risk factor for cardiovascular and neurodegenerative diseases and most forms of cancer. Research into the molecular basis of aging has answered a few questions and opened many more. Unlike mammals, some species of turtles and tortoises (testudines) have little or no evidence of senescence over extremely long lives. It has long been known that caloric restriction alone can prolong the life span of animals, including mammals. Some evidence suggests that calorically restricted mice also remain healthier for a longer time. Drugs that mimic caloric restriction have been shown to increase life span in the nematode Caenorhabditis elegans, as well as other species, including mice. Metformin and rapamycin each increase life span in these species when given alone and appear to have synergistic effects when given together. Sirtuins, a class of endogenous protein deacetylase enzymes, may be linked to life span in some species, but activators (such as resveratrol) of certain sirtuins have not been shown to prolong life in mice. Assuming that safer alternatives ...