Aging & Longevity

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Our previous study identified CD4 cytotoxic T lymphocytes (CD4 CTLs) as a hallmark of supercentenarians. CD4 CTLs have primarily been studied in disease contexts; however, their role in healthy aging remains unclear. Using single-cell immune profiling, we analyzed T cells from supercentenarians and found that CD4 CTLs begin to expand around the age of 100, characterized by sequential CD27/CD28 loss without exhaustion. CD4 CTLs were dominated by large clones, with top clones averaging 33.3%,...

Air pollution is the leading environmental cause of disease burden worldwide and is increasingly recognized as a potent driver of accelerated biological aging. Rather than acting through organ-specific toxicity alone, air pollutants appear to affect the fundamental hallmarks of aging itself, including oxidative stress, chronic inflammation, epigenetic dysregulation, telomere attrition, mitochondrial dysfunction, and cellular senescence. The pollutants of greatest concern are fine and ultrafine...

Aging features two linked immune traits: immunosenescence and chronic low-grade inflammaging. Other than senescent lymphocytes, pathologically remodelled macrophages are key drivers of age-related immune dysfunction, mainly via tryptophan (Trp) metabolism through the kynurenine pathway (KP) and microbiota-related indole pathway. This review suggests a bidirectional amplification loop model, in which dysbiosis of the microbiota in the aged gut causes decreased production of microbial indoles and...

Regulatory T (T(reg)) cells prevent autoimmune diseases but limit antitumor immunity. Tumor‑infiltrating Treg (Ti‑T(reg)) cells exhibit metabolic traits as potential antitumor targets. Here, we find that Ti-T(reg) cells upregulate glutamate dehydrogenase 1 (GDH1), increasing α-ketoglutarate (α-KG) levels. Elevated GDH1 in Ti-T(reg) cells accelerates tumor progression. Mechanistically, in a lactate rich microenvironment, GDH1 lactylation boosts α-KG production to fuel ALKBH5-mediated Wnt2...

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CONCLUSIONS: In our sample of studies evaluating CKD palliative care interventions, limited quality domains were addressed, a variety of measurement tools were used, and less than a quarter of studies were conducted only in older adults. Future research should address the holistic nature of palliative care, apply standardized instruments, and increase inclusion of older adults.

CONCLUSIONS: These findings highlight the adverse association of central adiposity and the limitations of BMI-only classification for mortality risk stratification in older adults.

CONCLUSIONS: Significant gaps exist in the integration of geriatric competencies across postgraduate medical training programs. Coordinated efforts are needed to integrate and assess these competencies to prepare physicians to care for aging populations.

CONCLUSION: These findings suggest that abdominal CT-derived liver attenuation and relative adiposity phenotypes may capture systemic tissue-level metabolic variations relevant to MRI-derived brain aging in women.

Alzheimer's disease (AD) has long been framed around amyloid-beta (Aβ) and tau pathology, yet mounting evidence indicates that dysfunctional microglia-astrocyte crosstalk is an important, and often underappreciated, contributor to disease progression that operates alongside-rather than in place of-neuronal, vascular, and proteinopathic mechanisms. Here we propose a three-stage framework in which glial communication transitions from silent vulnerability through organized defense to maladaptive...

CONCLUSIONS: Cardiorespiratory fitness seems to be a determinant of the resting metabolic rate in older adults, and lower 1-MET values would be expected in individuals with poorer vs. higher VO(2peak).

This perspective distinguishes two standards that are often used as if they were interchangeable. Optimal health is a standard built by medicine and expressed through guideline targets and biomarkers. Adequate health is the threshold of functioning that allows a person to live in a way they themselves experience as sufficient and dignified. Building on the concept of homeodynamic space as the biological substrate of adequate independence, on the older salutogenic tradition that asked what...

Understanding how osteoblasts build and remodel bone matrix in vivo remains a fundamental challenge because cellular metabolism and matrix turnover are difficult to resolve across time and space within mineralized tissues. Here, we developed an integrated imaging platform combining stable isotope labeling with correlative electron microscopy and nanoscale secondary ion mass spectrometry (NanoSIMS) to visualize bone cell metabolism and matrix dynamics at nanometer resolution in vivo. This...

The consequence of enhanced energy metabolism for health and life span of organisms is a fundamental yet controversially discussed issue of life and aging among others because of the fact that increasing energy metabolism often entails the risk of oxidative damage. To resolve this paradox, we introduce the bacterial-derived lipoic acid protein ligase A (LplA) as an orthogonal and defined molecular tool to enhance energy metabolism and at the same time to foster a low oxidative stress...

Ding et al. mapped over 7,000 plasma proteins to more than 40 cell types and developed machine learning aging clocks across 60,000 individuals, demonstrating that cell-type-specific biological aging is heterogeneous, measurable from blood alone, and powerfully predictive of neurodegenerative disease, cancer, and mortality up to 15 years before clinical onset.¹.

High-throughput single-cell omics of non-human primate brain tissue provides a powerful platform to investigate the molecular basis of brain aging. Here, we present a comprehensive transcriptomic and chromatin accessibility atlas of 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques spanning the adult lifespan, including exceptionally old individuals. Our analyses reveal dynamic, cell-subtype- and region-specific age-related changes in core brain functions, including...

In a Nature Medicine study, Tian et al. identify larger biological age gaps associated with early-onset lung, colorectal, and uterine cancers across birth cohorts. These findings position biological age as an integrative marker of physiological dysregulation. Future work combining aging clocks and mutational signatures could distinguish tumor-promoting states from tumor-initiating exposures.

Advanced age is accompanied by progressive metabolic, nutritional, mitochondrial, and neuroimmune dysregulation, which may increase susceptibility to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), highlighting the need to identify modifiable mechanisms that influence disease initiation and progression. Increasing evidence indicates that nutrition, sleep, and circadian rhythms function as an interconnected biological network regulating metabolic...

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