Is human aging still mysterious enough to be left only to scientists?

Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.

The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.

Recent increases in infectious disease mortality and concern about emerging infections warrant an examination of longer-term trends. To describe trends in infectious disease mortality in the United States during the 20th century. Descriptive study of infectious disease mortality in the United States. Deaths due to infectious diseases from 1900 to 1996 were tallied by using mortality tables. Trends in age-specific infectious disease mortality were examined by using age-specific death rates for 9 common infectious causes of death. Persons who died in the United States between 1900 and 1996. Crude and age-adjusted mortality rates. Infectious disease mortality declined during the first 8 decades of the 20th century from 797 deaths per 100000 in 1900 to 36 deaths per 100000 in 1980. From 1981 to 1995, the mortality rate increased to a peak of 63 deaths per 100000 in 1995 and declined to 59 deaths per 100000 in 1996. The decline was interrupted by a sharp spike in mortality caused by the 1918 influenza epidemic. From 1938 to 1952, the decline was particularly rapid, with mortality decreasing 8.2% per year. Pneumonia and influenza were responsible for the largest number of infectious disease deaths throughout the century. Tuberculosis caused almost as many deaths as pneumonia and influenza early in the century, but tuberculosis mortality dropped off sharply after 1945. Infectious disease mortality increased in the 1980s and early 1990s in persons aged 25 years and older and was mainly due to the emergence of the acquired immunodeficiency syndrome (AIDS) in 25- to 64-year-olds and, to a lesser degree, to increases in pneumonia and influenza deaths among persons aged 65 years and older. There was considerable year-to-year variability in infectious disease mortality, especially for the youngest and oldest age groups. Although most of the 20th century has been marked by declining infectious disease mortality, substantial year-to-year variation as well as recent increases emphasize the dynamic nature of infectious diseases and the need for preparedness to address them.