Thymic involution is the process by which the thymus shrinks with age and produces fewer T cells, impairing immunity and increasing the risk of infection in older adults. In addition, thymic involution increases the risk of cancer and autoimmunity with age.
However, research has identified some of the mechanisms of thymic involution and highlighted possible strategies to improve immunity:
The thymus is a lymphoid organ located behind the sternum and near the heart. Its primary purpose is to produce mature T cells, a type of white blood cell involved in allergies, autoimmunity, and immunity against pathogens. T cell maturation begins at birth and is most active in early life when pathogens and allergens are encountered by the immune system for the first time. T cell production drops sharply after adolescence, followed by a sharp rise in the rate of thymic involution after age forty.
New T cells arise from hematopoietic progenitor cells (i.e., blood stem cells) in the bone marrow and migrate to the thymus for maturation. In the thymus, naive T cells will mature into one of four main populations.
With such an important set of responsibilities, it is unsurprising that a decline in T cell-mediated immunity contributes to debilitating age-related illnesses:
Below is a selection of summaries from recent research investigating the role of thymic involution in health and disease.
People tend to be less physically active with age; however, older adults who exercise slow the progression of aging and disease. In addition to the well-documented effects of exercise on cardiovascular health, exercise training improves immunity through a variety of mechanisms, including the increased production of naive T cells, which can be programmed to help fight infection. Findings of one report demonstrate better T cell immunity among older adult cyclists.
The authors recruited 125 trained amateur cyclists and 75 adults who did not participate in regular intense exercise between the ages of 55 and 80 years old for the study. They also recruited 55 young adults between 20 and 36 years old who did not exercise vigorously. The researchers collected a blood sample from each participant in order to measure hormones, cytokines, and the type and number of peripheral blood mononuclear cells, white blood cells in the blood that include monocytes, T cells, B cells, and natural killer cells.
The number of young T cells (those that had recently migrated from the bone marrow to the thymus) and naive T cells was greater in older adults who cycled than older adults who did not cycle. Older adult cyclists had the same number of young T cells as the young adult participants. While older adult non-cyclists had a greater number of senescent immune cells, which are proinflammatory aged cells, than young adults, older adult cyclists did not have increased cellular senescence compared to young adults. Finally, older adult cyclists had markedly lower levels of the pro-inflammatory cytokine interleukin-6 and higher levels of interleukin-7, which slow thymus shrinkage.
These results demonstrate that intense exercise training in older adults increases naive T cell release, reduces the burden of senescent cells, and lowers inflammation, which may translate to slower thymic involution and better immunity with aging.
The human immune system loses function with age in a process known as immunosenescence. Previous research has reported on the ability of a number of drugs to impact the aging process; however, these studies have not measured the ability to reverse epigenetic aging. Research from epigenetics expert Steve Horvath is the first to demonstrate the reversal of epigenetic aging and immunosenescence of the thymus with drug therapy.
Nine participants between the ages of 51 and 65 years were given a drug protocol that included recombinant human growth hormone to reverse signs of immunosenescence. Because growth hormone can increase insulin production to a harmful degree, the investigators used metformin, a common diabetes drug, and dehydroepiandrosterone, a steroid precursor, to control symptoms of diabetes. They collected white blood cells to measure immune characteristics and epigenetic age.
Following one year of treatment, the investigators reported an average decrease in epigenetic age of 1.5 years over baseline, meaning they reversed epigenetic age by 2.5 years over the course of the study. Participants demonstrated an increase in T cell production and an increase in the leukocyte/monocyte ratio, a measure of immune cell populations that is associated with less inflammation and lower rates of several cancers. Monocytes use large quantities of nicotinamide adenine dinucleotide (NAD+), which is an important energy source for cells. The investigators suggested this decrease in monocytes and subsequent increase in NAD+ may be responsible for the reversal of epigenetic aging.
The main purpose of this pilot trial was to determine the safety and efficacy of the intervention. Larger studies with a control group are needed to expand on these results.
Q: What does emerging science say about the causes and treatment of autoimmune diseases such as multiple sclerosis, lupus, and others?
A: Research describes the gut microbiota as a central mediator of immune dysfunction in the development of autoimmune diseases. Therefore, probiotics and intestinal microbiota transplantation may be novel therapeutic targets. Fasting is another therapy under investigation for treating autoimmunity. One report in humans showed that a fasting-mimicking diet reduced autoimmunity and promoted immune regeneration. To learn more about the fasting-mimicking diet used by the researchers in this study, see our episode with fasting and longevity expert, Dr. Valter Longo.