Thymic Involution
Thymic involution featured article
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:
- By activating PPAR-gamma, a protein that regulates fat metabolism, caloric restriction reduced the rate of thymic involution in mice and increased the number and diversity of circulating T cells.
- T cells from participants with obesity tended to be less diverse, a finding supported by a study in mice that found that diet-induced obesity increased immunosenescence, a type of advanced cell aging, and thymic involution in mice. This suggests maintaining a healthy weight may slow thymic involution and loss of T cell immunity.
- Stress increased the rate of thymic involution in...
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Thymic involution
Thymic involution denotes age-induced epithelial atrophy and adipogenesis driven by FOXN1 decline, sex steroids, proinflammatory cytokines, reducing naïve T-cell output.
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The thymus establishes a diverse immune defense early in life, yet much of its tissue is gradually replaced by fat with aging. A new study examined whether adults who retain more of that tissue have different long-term health outcomes than those who don't.
Researchers analyzed chest scans and health records from more than 27,000 participants in two large studies, one focused on lung cancer screening and the other on cardiovascular health. Using artificial intelligence (AI), the researchers assessed how well thymic tissue was preserved on chest scans as a potential indicator of thymus function. They then compared people with the highest and lowest scores to see whether they differed in their risk of dying over the next 12 years or developing lung cancer over six years.
- Participants with higher thymus scores had a substantially lower risk of dying over 12 years. In the lung screening group, mortality was 13.4% compared with 25.5% among those with the lowest scores.
- Those with higher scores were less likely to develop lung cancer over six years, with rates of 3.4% versus 5.3%.
- Cardiovascular mortality was also lower among participants with higher scores, at 2.9% versus 7.5% over 12 years.
- Lower thymus scores were associated with heavier smoking, obesity, lower physical activity, elevated inflammatory markers, and less favorable metabolic markers, including higher blood sugar, triglycerides, and blood pressure. Higher HDL cholesterol was associated with higher scores.
The T cells that mature in the thymus are a type of immune cell that does more than fight infections. They also help recognize cancer cells and regulate inflammation, which plays an important role in atherosclerosis. But chronic inflammation may also accelerate thymus decline. This could help explain the links with lifestyle factors, since smoking and obesity tend to promote inflammation, while physical activity can help reduce it. However, it remains unclear whether lifestyle changes can actually preserve thymus function.
If thymic decline contributes to the development of disease, it may represent a shared vulnerability across several age-related conditions, rather than just another sign of aging. This raises the possibility that preserving thymus function could help maintain immune defenses as we age.
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Adults with more preserved thymic tissue on CT had lower cardiovascular mortality in two cohorts, giving thymic-rejuvenation research a sharper outcome to test. www.massgeneralbrigham.org
The thymus trains developing T cells, then typically shrinks and becomes fatty with age, a process called thymic involution. Its appearance in adulthood may preserve information about aging in both the immune system and the body more broadly.
Researchers trained an imaging model to estimate preserved, non-fatty thymic tissue from chest CT scans, then tested whether the score tracked health outcomes in a lung-screening cohort and the Framingham Heart Study.
- Adults with the most preserved thymic tissue had lower cardiovascular mortality in both cohorts. In the lung-screening cohort, 12-year cardiovascular mortality was 2.9% in the highest score quartile versus 7.5% in the lowest; in Framingham, it was 0.3% versus 3.9%.
- Higher scores also tracked lower all-cause mortality and lung cancer incidence in the lung-screening cohort, but the all-cause association was no longer significant after full adjustment in Framingham.
The score measured thymic appearance—not T-cell output or immune function—and its quartiles were relative to each cohort rather than universal clinical cutoffs. The analysis cannot show whether preserving thymic tissue improves health or whether healthier people simply retain more of it. Smoking, body weight, physical activity, and inflammation tracked with the score, but the study did not test whether changing those factors restores the thymus.
That immune-aging context is discussed in Rhonda's episode on exercise and immune aging. Here, the replicated cardiovascular signal suggests that thymic appearance may be a visible marker of systemic aging, giving thymic-rejuvenation research a sharper outcome to test.
Press Release: Long Dismissed in Adult Health, the Thymus May Be Critical for Longevity and Cancer Treatment
Study: Thymic health consequences in adults -
Long-term distance cycling reduces hallmarks of aging: thymic involution - "cyclists' thymuses were making as many T cells as those of a young person" www.sciencedaily.com
From the article:
The study recruited 125 amateur cyclists aged 55 to 79, 84 of which were male and 41 were female. The men had to be able to cycle 100 km in under 6.5 hours, while the women had to be able to cycle 60 km in 5.5 hours.
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The cyclists also did not increase their body fat or cholesterol levels with age and the men’s testosterone levels also remained high, suggesting that they may have avoided most of the male menopause.
More surprisingly, the study also revealed that the benefits of exercise extend beyond muscle as the cyclists also had an immune system that did not seem to have aged either.
An organ called the thymus, which makes immune cells called T cells, starts to shrink from the age of 20 and makes less T cells. In this study, however, the cyclists' thymuses were making as many T cells as those of a young person.
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Experimental drug protocol demonstrates reversal of epigenetic aging. www.ncbi.nlm.nih.gov
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.
The thymus is an immune organ necessary for the development of T cell populations. After the age of approximately 63, a process called thymic involution severely impairs T cell function and is linked to increases in cancer, infection, autoimmune conditions, chronic inflammation, and heart disease.
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 authors used metformin, a common diabetes drug, and dehydroepiandrosterone, a steroid precursor, to control symptoms of diabetes. The investigators collected white blood cells to measure immune characteristics and epigenetic age.
Following one year of treatment, the authors 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 a lot of nicotinamide adenine dinucleotide (NAD+), which is an important energy source for cells. The authors 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 study treatment. Larger studies with a control group are needed to expand on these results.