👤 Hamza Hadj Abdallah

Aging is accompanied by a progressive decline in immune function, known as immunosenescence, and by a chronic low-grade inflammatory state, termed inflammaging. Both conditions contribute to increased susceptibility to infections, reduced vaccine responses, and the development of age-related diseases. Emerging evidence suggests that intermittent fasting (IF), a dietary pattern that alternates between periods of fasting and feeding, may influence pathways associated with immune aging across mid-life and older adulthood. This review explores how IF may exert immunoregulatory effects through metabolic remodeling, cellular stress responses, and inflammatory signaling. Preclinical and human studies indicate that IF attenuates pro-inflammatory cytokine production, enhances autophagy, and improves immune cell function, potentially delaying immunosenescence and reducing inflammaging in middle-aged and older populations. Additionally, IF may protect against neuroinflammation and cognitive decline by reducing oxidative stress, activating AMPK-SIRT1 and ketone signaling via β-hydroxybutyrate (BHB), enhancing neuroplasticity, upregulating brain-derived neurotrophic factor, and suppressing pro-inflammatory cytokines, inflammation, and frailty in the aging brain. However, most evidence comes from short- to medium-term studies in selected, relatively healthy populations, with benefits often similar to those of continuous calorie restriction, and there is limited data on long-term safety, adverse effects, and outcomes in frail older adults. By reducing oxidative stress and inflammaging, IF may mitigate frailty in older adults or delay its progression when initiated earlier. By integrating insights from immunometabolism and gerontology, this review highlights the potential role of IF as a non-pharmacological strategy to promote healthy immune aging and support functional outcomes in older adults. However, evidence in frail older adults remains limited, and randomized trials in this population are warranted. Future research should directly compare IF with isocaloric non-fasting regimens, include long-term follow-up, and carefully characterize safety and adherence in high-risk groups before IF can be routinely recommended for immune aging. Show less

Congenital heart defects represent a major global health burden, affecting nearly one million newborns annually. Identifying the underlying genetic causes is essential for improved diagnosis, patient management, and genetic counseling. We conducted a cytogenetic study integrating conventional karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA 44 K) in 20 Tunisian patients presenting syndromic CHDs and referred to our Genetics Department. CMA identified pathogenic copy number variations in four patients. These included an inherited 11 Mb deletion at 9p24.2 together with a 10 Mb duplication of 20pter; a de novo 1.2 Mb deletion at 15q26.2 with an 11 Mb duplication at 2q36.3; a de novo 113 kb deletion at 17q21.32; and a de novo 48 Mb duplication at 8q22. Several CNVs overlapped known deletion/duplication syndromes, some with previously infrequent cardiac involvement. Genotype-phenotype correlations enabled prioritization of CHD relevant genes including DOCK8, HTR2B, KANSL1, ZFPM2, and TRPS1, whose dosage sensitivity and interactions with cardiac developmental pathways may contribute to the observed phenotypes. This study reinforces the clinical utility of CMA in detecting cryptic chromosomal abnormalities in syndromic CHD. The identified CNVs and gene candidates offer new insights into CHD genetic architecture and support CMA as a first-tier diagnostic tool. These findings highlight the contribution of rare, pathogenic CNVs in syndromic cases and suggest their integration into refined diagnostic and counseling strategies. Further functional studies are necessary to elucidate the roles of these candidates in cardiogenesis. Show less

Systemic light chain amyloidosis (AL) arises from monoclonal immunoglobulin light chains, but determinants of progression from precursor states remain poorly defined. In a cross-sectional cohort comprising 1950 systemic AL patients diagnosed 2010-2024, 258 (13.2%) patients with a previously diagnosed plasma cell disorder (PCD) were compared to patients with no prior PCD diagnosis. Patients with monoclonal gammopathy of undetermined signficance (MGUS) and smoldering multiple myeloma (SMM) in the former group had lower difference between involved and uninvolved FLCs (dFLC), higher M-protein, and lower rates of t(11;14) at AL diagnosis. Patients developing AL from SMM had a shorter time to AL (median 34.2 versus 61.3 months) and higher dFLC (median 28.9 versus 11.0 mg/dl) compared to those from MGUS. Patients developing AL after known multiple myeloma (MM) or lymphoplasmacytic lymphoma (LPL) commonly lacked deep hematologic response before AL (≤ very good partial response in 78% of MM, 100% of LPL patients). We additionally studied longitudinally followed cohorts of 3,966 MGUS and 426 (SMM) patients with longitudinal FLC measurements and matched follow-up, in which 1.8% of MGUS and 7.2% of SMM patients developed AL. Those patients who developed AL showed markedly higher dFLC at MGUS/SMM diagnosis and more frequent λ restriction and rates of t(11;14). Higher dFLC was associated with progressively earlier AL development; a 10% cumulative risk occurred at 20 months for patients with a dFLC >80 mg/dL but was not reached if dFLC <10 mg/dL at an estimated median follow-up of 86 months. In multivariable analysis, dFLC >6.4 mg/dL (HR 11.3) and λ isotype (HR 3.6) independently predicted AL, whereas heavy chain secretion was associated with lower risk (HR 0.2 for IgG). These findings indicate that AL risk is primarily driven by cumulative light chain exposure, refining our knowledge of AL pathophysiology and providing guidance for follow-up of patients with elevated dFLC. Show less

The role of the prokineticin 2 pathway in human reproduction, olfactory bulb morphogenesis, and gonadotropin-releasing hormone secretion is well established. Recent studies have highlighted the implication of di/oligogenic inheritance in this disorder. In the present study, we aimed to identify the genetic mechanisms that could explain incomplete penetrance in hypogonadotropic hypogonadism (HH). This study involved two unrelated Tunisian patients with HH, which was triggered by identifying a homozygous p.(Pro290Ser) mutation in the Show less