Aging & Longevity

CONCLUSIONS: Most main outcome measures in physical performance worsened over time across age groups while poor performance pattern was different between older males (strength) and females (functional mobility). We highlighted the importance of assessing strength, functional mobility, and postural control in older adults. Based on observed poor performance patterns across age groups by sex, sex-specific interventions should be implemented.

Mitochondrial calcium (mtCa^(2+)) uptake via the mitochondrial calcium uniporter (MCU) couples calcium homeostasis and energy metabolism. mtCa^(2+) uptake via MCU is rate-limiting for mitochondrial activation during muscle contraction, but its pathophysiological role and therapeutic application remain largely uncharacterized. By profiling human muscle biopsies, patient-derived myotubes, and preclinical models, we discovered a conserved downregulation of mitochondrial calcium uniporter regulator...

CONCLUSION: Machine learning algorithms, especially ensemble models, can effectively identify older adults at risk for ADL disorders. Increased outdoor activity, social engagement, and dietary adjustments are associated with a decreased risk of ADL deterioration. TRANSLATIONAL SIGNIFICANCE.

CONCLUSIONS: While the global burden of SCI is decreasing, the complex distribution across demographics and regions necessitates targeted prevention and treatment strategies to further reduce the burden and improve patient outcomes.

While it is well understood that mitochondrial DNA (mtDNA) deletion mutations cause incurable diseases and contribute to aging, little is known about the transcriptional products that arise from these DNA structural variants. We hypothesized that mitochondrial genomes containing deletion mutations express chimeric mitochondrial RNAs. To test this, we analyzed human and rat RNA sequencing data to identify, quantitate, and characterize chimeric mitochondrial RNAs. We observed increased chimeric...

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The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons....

Aberrant angiogenesis could contribute to the development of cognitive impairment and represent a therapeutic target for preventing dementia. However, most studies addressing angiogenesis and cognitive impairment focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in a pooled two-center sample from deeply phenotyped longitudinal human cohorts (n = 435; female...

Complex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that...

The lifestyle patterns of top athletes are highly disciplined, featuring strict exercise regimens, nutrition plans, and mental preparation, often beginning at a young age. Recently, it was shown that physically active individuals exhibit slowed epigenetic aging and better age-related outcomes. Here, we investigate whether the extreme intensity of physical activity of Olympic champions still has a beneficial effect on epigenetic aging. To test this hypothesis, we examined the epigenetic aging of...

OBJECTIVES: Nearly half of older adults experience somnolence, but the link between medications with somnolence as an adverse effect and somnolence is unclear. This study investigated the association between polypharmacy and somnolence symptoms (excessive sleepiness or long sleep duration).

Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (α-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in...

Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil. In this multi-player aging process, cellular senescence induces a change in the secretory phenotype, known as senescence-associated secretory phenotype (SASP), of many cells with the intention of...

Nickel-rich layered oxides are one of the most promising positive electrode active materials for high-energy Li-ion batteries. Unfortunately, the practical performance is inevitably circumscribed by the structural deterioration deriving from the Ni/Li antisite disorder, leading to severe capacity loss and life attenuation. Herein, we propose an economical and facile rejuvenation strategy by employing the magneto-electrochemical synergistic activation targeting the positive electrode in assembled...

The distribution of biomolecules within cells changes upon aging and diseases. To quantitatively determine the spatial distribution of components inside cells, we built the user-friendly open-source 3D-cell-image analysis platform Cell Detection and Analysis of Intensity Lounge (CellDetail). The algorithm within CellDetail is based on the concept of the dipole moment. CellDetail provides quantitative values for the distribution of the polarity proteins Cdc42 and Tubulin in young and aged...

Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8^(+) tissue resident memory T (T(RM)) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8^(+) T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8^(+) T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by...

Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein...

The identification of causal relationships between specific genes and social, behavioral, and health outcomes is challenging due to environmental confounding from population stratification and dynastic genetic effects. Existing methods to eliminate environmental confounding leverage random genetic variation resulting from recombination and require within-family dyadic genetic data (i.e., parent-child and/or sibling pairs), meaning they can only be applied in relatively small and selected...

Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the...

OBJECTIVE: Determine how preventable causes of death contribute to the life expectancy gap between Mexico and Spain.