Aging & Longevity

Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections and cancers. Here, we examined the role of regulatory T (Treg) cells on thymic regeneration. Treg cell frequencies increased in the thymus in various acute injury models. Depletion of Treg cells impaired thymic regeneration, impacting both the thymocyte compartment and the stromal cell compartment; adoptive transfer of Treg cells enhanced regeneration. Expansion of...

Because children have little temporal exposure to environment and aging, most pediatric neurological diseases are inherent, i.e. genetic. Since postnatal neurons and astrocytes are mostly non-replicating, gene therapy and genome editing present enormous promise in child neurology. Unlike in other organs, which are highly permissive to adeno-associated viruses (AAV), the mature blood-brain barrier (BBB) greatly limits circulating AAV distribution to the brain. Intrathecal administration improves...

Structural and functional changes in the entorhinal cortex (EC) are among the earliest signs of cognitive aging. Here, we ask whether a compromised cholinergic system influences early EC impairments and plays a primary role in EC cognition. We evaluated the relationship between loss of integrity of cholinergic inputs to the EC and cognitive deficits in otherwise healthy humans and mice. Using in vivo imaging (PET/MRI) in older humans and high-resolution imaging in wild-type mice and mice with...

CONCLUSION: Significant differences in autophagy activity were identified between young and aged DSS-induced mice. These findings underscore the potential therapeutic benefits of autophagy inhibition in elderly UC patients.

More complex occupations during adulthood may be associated with better cognition in later life. We used data from the Brazilian Longitudinal Study of Aging (ELSI) and the Mexican Health and Aging Study (MHAS) to investigate the association between occupational complexity and cognitive function. Using a regression-based approach, participants were classified as cognitively impaired or not. Occupation was categorized into four levels using the 2008 International Standard of Classification of...

Chronological age is an imperfect estimate of molecular aging. Epigenetic age, derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. We examine the bidirectional relationship between epigenetic age and brain health events (stroke, dementia, late-life depression) using data from 4,018 participants. Participants with a prior brain health event are 4% epigenetically older (β = 0.04, SE = 0.01), indicating these conditions are associated...

CONCLUSIONS: These results underscore the importance of addressing sarcopenia and related risk factors, including malnutrition, in the management and prevention of severe falls in the elderly population. Body composition analyzed in CT-scans could add value in this risk assessment. This analysis could be conducted opportunistically during CT scans performed for other purposes.

CONCLUSIONS: The global status of nutritional deficiency among older adults has improved since 1990, but the increasing prevalence of protein-energy malnutrition requires attention. Additionally, cross-country health inequalities persist, necessitating more efficient public health measures.

Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such...

Aging brings with it many health issues that can make life challenging. As much of the attention is given to non-communicable diseases, there are others which are slowly becoming a matter of great concern. One such issue is cognitive frailty, which is a high risk factor for dementia, falls, fractures and hospitalization. Though not yet declared a public health concern, it deserves early detection and prevention strategies. As it is reversible if treated on time, there is a need to look into its...

CONCLUSION AND IMPLICATIONS: CogStep1 demonstrated good sensitivity and PPV to identify objective cognitive impairment among older people referred to a memory clinic. Achieving excellent sensitivity and specificity values is challenging for a very short test. However, CogStep1 proved useful for risk-stratifying patients who can benefit from further cognitive assessment, biomarker measurements, and therapeutic management, especially in the context of new anti-amyloid therapies.

Senescence and loss of cochlear hair cells is an important pathologic basis of age-related hearing loss. Lipid droplet accumulation has previously been shown to play an important role in neurodegeneration; however, its role in age-related hearing loss has not yet been investigated. LXRβ/ABCA1 is a key pathway that regulates lipid metabolism, while its dysfunction can cause abnormal accumulation of lipid droplets in neurons, leading to neurodegeneration. In this study, we found that decreased...

Executive functions (EFs), encompassing inhibition, shifting, and updating as three fundamental subdomains, are typically characterized by a unity/diversity construct. However, given the dedifferentiation trend observed in aging, it remains controversial whether the construct of EFs in older adults becomes unidimensional or maintains unity/diversity. This study aims to explore and validate the construct of EFs in older adults. At the behavioral level, we conducted confirmatory factor analysis on...

Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O(2)) or hypoxic (1% O(2)) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated...

Glioblastoma multiforme (GBM) remains a therapeutic challenge due to its aggressive nature and recurrence. This study establishes a radioresistant GBM cell model through repeated irradiation and observes a cellular senescence-like phenotype in these cells. Comprehensive genomic and transcriptomic analyses identify IFI16 as a central regulator of this phenotype and contributes to radioresistance. IFI16 activates HMOX1 transcription thereby attenuating ferroptosis by reducing lipid peroxidation,...

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Various anti-aging interventions show promise in extending lifespan, but many are ineffective or even harmful to healthspan. Ginkgolide B (GB), derived from Ginkgo biloba, reduces aging-related morbidities such as osteoporosis, yet its effects on healthspan and longevity have not been fully understood. In this study, we found that continuous oral administration of GB to female mice beginning at 20 months of age extended median survival and median lifespan by 30% and 8.5%, respectively. GB...

Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has also been implicated in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we report the finding that 753b, a dual BCL-xL/BCL-2 proteolysis-targeting chimera (PROTAC), acts as a potent and liver-tropic senolytic. We found that...

The peripheral immune system communicates with the brain through complex anatomical routes involving the skull, the brain borders, circumventricular organs and peripheral nerves. These immune-brain communication pathways were classically considered to be dormant under physiological conditions and active only in cases of infection or damage. Yet, peripheral immune cells and signals are key in brain development, function and maintenance. In this Perspective, we propose an alternative framework for...

Dietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that not adding any of the metal ions to the diet adversely affects reproduction and lifespan. By contrast, food with no added Zn negatively impacts reproduction but does not adversely affect maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Specifically, it indicates that female flies stop producing eggs to conserve their body Zn for...