Immunosenescence

This prospective observational cohort study aims to investigate the relationship between immunosenescence and infectious diseases in older adults. Individuals aged 60 years and older, including elderly patients with infections and healthy controls, will be enrolled and followed longitudinally. Clinical information, laboratory test results, and health assessment data will be collected. Biological specimens, including peripheral blood, urine, stool, sputum, and nasopharyngeal swabs, will be obtained during enrollment and follow-up. Participants will undergo regular assessments of health status, infection events, and aging-related clinical characteristics. The study will evaluate age-related changes in immune function, immune cell composition, immune receptor repertoires, epigenetic characteristics, metabolic profiles, and respiratory and gut microbiota. By integrating clinical and multi-omics data, the study aims to identify biomarkers associated with immunosenescence, susceptibility to infection, disease severity, and clinical outcomes in older adults. The results are expected to improve understanding of the mechanisms linking aging, immune dysfunction, and infectious diseases, and to support the development of predictive models and preventive strategies for infection management and healthy aging in elderly populations.

As population aging accelerates, infectious diseases have become a major factor affecting the health, quality of life, and survival outcomes of older adults. Immunosenescence, chronic low-grade inflammation (inflammaging), and dysbiosis of the respiratory and gut microbiota are considered important mechanisms underlying increased susceptibility to infection and a higher risk of severe disease in older adults. However, the interactions among these factors and their impact on infection-related outcomes remain incompletely understood. Building upon a previously established pilot cohort of older adults, this study aims to further identify and validate key biological characteristics and risk factors associated with infectious diseases through large-scale population follow-up. A large prospective cohort of older adults will be established, while retrospective healthcare data collected since 2019 will also be integrated. Demographic information, comorbidities, medication history, infection-related clinical data, and biological specimens, including blood, urine, fecal, and respiratory samples, will be collected for long-term longitudinal follow-up. By integrating immunological assessments, immune repertoire analyses, microbiome profiling, and other multi-omics technologies, this study will systematically evaluate the effects of immunosenescence, respiratory and gut microbiome alterations, and environmental and climatic factors on the occurrence, severity, and prognosis of infectious diseases in older adults. The study aims to identify key biomarkers and microbial signatures associated with infection risk and to develop risk prediction and early warning models for infectious diseases in older adults, thereby providing scientific evidence for precision prevention, optimized clinical management, and public health decision-making in aging populations.

This study will explore whether a daily probiotic drink containing Lactobacillus casei Shirota (LcS) can help improve immune function and reduce inflammation in women going through the menopausal transition. Hormonal changes during this stage of life can affect the immune system, gut health, and skin, sometimes leading to increased inflammation or conditions such as eczema, acne or rosacea. Participants will consume either a low-sugar LcS probiotic drink or a skimmed milk control drink every day for eight weeks. The study will assess markers of immune ageing, inflammation, skin health, wellbeing, and hormone levels. The results will help determine whether a safe, non-hormonal probiotic approach may support immune and skin health during the menopausal transition.

The diagnosis of respiratory viral infections is mainly based on PCR tests targeting the DNA or RNA of suspected viruses, including SARS-CoV-2, RSV and influenza viruses. However, this method is limited because it only tests for a small number of viruses, while many other pathogens can cause similar symptoms. As a result, respiratory viral infections are often underdiagnosed because not all possible viruses are systematically tested for. Another limitation of PCR tests is that they can detect residual viral genetic material long after the infection has ended, making it difficult to distinguish between an active infection and a past one. Viral load can help interpret the result, but it is not always reliable. It is therefore essential to have complementary markers that can indicate whether the detected virus is still in the active replication phase. An innovative approach is to measure the host's immune response, in particular the production of type I interferons (IFN-I), which are markers of active viral infection. Studies have shown that joint analysis of the IFN-I/III response and PCR tests improves the detection of viral respiratory infections by better discriminating between active infections. This method shows promise for refining diagnosis, particularly in cases where the viral load is low or ambiguous. These advances are particularly important for older patients, in whom viral infections have a severe impact. Ageing leads to a decline in immune function (immunosenescence), including a reduction in IFN-I production. This alteration could further complicate the interpretation of immune biomarkers in older people, highlighting the need to establish reference values specific to this population. In this context, the RESPIGERIA study (compliance with MR004 No. 24-5127) was launched to evaluate the IFN response in geriatric hospitalised patients with respiratory viral infections. However, there is still a lack of reference data on the IFN response in uninfected older individuals. Establishing a baseline IFN score in this population is essential in order to adapt diagnostic tools to age-related specificities.

Background: Immunosenescence is an age-related decline in immune function, associated with chronic low-grade inflammation, increased morbidity, and functional impairment in older adults. Aerobic exercise has been proposed as an effective non-pharmacological strategy to counteract these alterations; however, evidence from randomized-controlled trials (RCTs), particularly in institutionalized elderly populations, remains scarce and methodologically limited. Objective: This study protocol aims to investigate the effects of short- and medium-term aerobic exercise programs on immunosenescence in institutionalized older adults, as well as to analyze the impact of a detraining period and a subsequent reintervention. Methods: A stratified RCT will be conducted with institutionalized adults aged ≥60 years, randomly allocated to an aerobic exercise group or a control group. The intervention consists of a supervised 12-week moderate-intensity aerobic exercise program (three sessions/week), followed by a 4-week detraining period and a 4-week reintervention. Assessments will be performed at five time points. Primary outcomes include immunological and analytical parameters assessed by spectral flow cytometry and multiplex cytokine analysis. Secondary outcomes include anthropometry, functional capacity, hemodynamic parameters, heart rate variability, and psychological indicators. Expected Results: Aerobic exercise is expected to induce favorable immunological adaptations, partially reverse immunosenescence, and improve functional and psychosocial outcomes.

People with HIV who drink alcohol are at increased risk for accelerated aging biology, including increased immune senescence. This randomized, double-blind, crossover clinical trial evaluates two generally recognized as safe (GRAS) microbiota-targeted interventions on immune senescence biomarkers.

This is a follow-up study of a previously completed randomized controlled trial (NCT06827873) that investigated the effects of oral supplements on influenza vaccine response in adults aged 60-70 years. The original study was completed in April 2025, with participants receiving either TUDCA (Tauro Ursodesoxy Cholic Acid) supplementation, fatty acid supplementation, or placebo during influenza vaccination. The primary objectives of this follow-up study are to: 1. Evaluate the durability of vaccine-induced antibody responses approximately 8 months post-vaccination 2. Assess the persistence of immune memory cells, particularly long-lived plasma cells and memory B cells 3. Compare long-term immune responses between the TUDCA supplementation group and placebo group This observational follow-up involves a single visit where participants will: 1. Provide one blood sample for antibody and immune cell analysis 2. No intervention or vaccination will be administered The study will specifically focus on B cell subsets through flow cytometry analysis, including total B cells, memory B cells, plasma cells, and long-lived plasma cells. This research aims to determine whether TUDCA supplementation can enhance the durability of vaccine-induced immunity in older adults.

The aim of this study is to investigate the effects of a four-week time-restricted eating (TRE) intervention on autophagy, immune function, and vaccine response to a seasonal influenza and COVID-19 vaccines in older healthy subjects.

B cube is a new generation cohort to study the determinants and natural history of brain aging, using molecular epidemiology, in a representative sample (N=2000) of the general population from the age of 55 (the approximate age of onset of the first cognitive disorders and a target population particularly receptive to prevention messages). Special interest will be given to nutrition, a promising environmental exposure for prevention.

The ageing of our country is increasing and the ageing of the population has led to a significant increase in aging related diseases. During the aging process of the organism, cellular senescence can occur in all systems of the body, of which the senescence of the immune system is called immunosenescence. Some studies have shown that metabolic disorders can also trigger aging. This study investigated the effect of nicotinamide mononucleotide (NMN) supplementation on immunosenescence in middle-aged and elderly people through a placebo-controlled long-range clinical trail, aiming to provide a new method to improve immunosenescence. The effects of NMN supplementation on glucose and lipid metabolic indexes, body composition and telomere length of peripheral blood cells are also investigated, which may open up new ideas for the prevention and treatment of glucose and lipid metabolic diseases.

The TRIIM-X trial is an expanded pilot clinical study that will evaluate a personalized combination treatment regimen for thymus regeneration. The thymus is a part of the immune system that declines markedly with age, and regenerating it may prevent or reverse key aspects of immunosenescence (immune system aging) and potentially prevent or reverse key parts of the aging process more generally. The study will evaluate biomarkers for epigenetic aging and immunosenescence, as well as evaluate established clinical measures and risk factors for prevention of physical frailty, cancer, cardiovascular disease, diabetes, dementia, and also infectious diseases, including flu and COVID-19. The study uses multiple agents in combination with personalized doses of recombinant human growth hormone (somatropin), metformin, and DHEA, in a similar manner to how the combination treatment was applied in the earlier TRIIM trial at Stanford, which demonstrated strong statistical significance for the primary efficacy endpoints that will be evaluated in TRIIM-X. Somatropin is approved by the FDA for adult growth hormone deficiency and its use in the study is guided by prior safety data established for that use and also based on safety data available on its prior use in the TRIIM trial and in clinical practice in healthy elderly individuals. There will also be control groups that enable testing of biomarker variability and the contribution of individual medications within the combination treatment. The objective of the study is to obtain information needed for designing an effective personalized and adaptive treatment regimen for a larger and more diverse study population, and to obtain additional proof of principle for the new use of the medications and biomarkers for preventive medicine. The duration of treatment in the TRIIM-X trial will be 12 months.