Aging & Longevity

The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression. Dysregulation of the mTOR pathway is linked to numerous human diseases, including cancer,...

Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in...

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical...

Earth's old animals are in decline. Despite this, emerging research is revealing the vital contributions of older individuals to cultural transmission, population dynamics, and ecosystem processes and services. Often the largest and most experienced, old individuals are most valued by humans and make important contributions to reproduction, information acquisition and cultural transmission, trophic dynamics, and resistance and resilience to natural and anthropogenic disturbance. These...

Surface passivation has driven the rapid increase in the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, state-of-the-art surface passivation techniques rely on ammonium ligands that suffer deprotonation under light and thermal stress. We developed a library of amidinium ligands, of interest for their resonance effect-enhanced N-H bonds that may resist deprotonation, to increase the thermal stability of passivation layers on perovskite surfaces. This strategy...

Blue zones, supposed havens of longevity, have become a global brand. But skeptics think they rest on shaky science.

CONCLUSIONS: Videoconference based neuropsychological assessment can be as precise as in-person. Calibration of ability estimates using latent variable measurement models can address measurement differences and generate scores without evidence of systematic bias.

Identifying early predictors of cognitive decline and at-risk individuals is essential for timely intervention and prevention of dementia. This study aimed to detect neurobiological changes and factors related to cognitive performance in the Metropolit 1953 Danish male birth cohort. We analyzed data from 582 participants, aged 57-68 years, using machine learning techniques to group cognitive trajectories into four clusters differentiating high- and low-performing groups. These clusters were then...

Prior studies have shown that interrupting the growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling axis extends laboratory mouse lifespan, but confounding effects of additional gene or hormone deficiencies that exist in commonly used models of GH/IGF-I interruption obscure the specific effect of GH on longevity. We address this issue by using mice with a specific knockout of the GH gene and show that both males and females on a mixed genetic background display extended lifespans...

Production of specialized proresolving mediators (SPMs) during the resolution phase in the acute inflammatory response is key to orchestrating complete resolution. Here, we uncovered a trihydroxy resolvin in fresh human saliva. We identified and determined its complete stereochemistry as 7S,16R,17R-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (17R-RvD2) using total organic synthesis and matching of physical properties. The 17R-RvD2 was produced by activated human M2-like macrophages,...

NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain. NKG2D/Dap10-12 T cells elicit compelling efficacy, eradicating or controlling NKG2DL-expressing tumors in several established xenograft models. Importantly, durable responses, long-term survival, and rejection of tumor...

Alzheimer's disease (AD), commonly known as senile dementia, is a neurodegenerative disease with insidious onset and gradually worsening course. The brain is particularly sensitive to senescence, and neuronal senescence is an important risk factor for the occurrence of AD. However, the exact pathogenesis between neuronal senescence and AD has not been fully elucidated so far. Neuronal senescence is characterized by the permanent stagnation of the cell cycle, and the changes in its structure,...

Skeletal muscles are essential for locomotion and body metabolism regulation. As muscles age, they lose strength, elasticity, and metabolic capability, leading to ineffective motion and metabolic derangement. Both cellular and extracellular alterations significantly influence muscle aging. Satellite cells (SCs), the primary muscle stem cells responsible for muscle regeneration, become exhausted, resulting in diminished population and functionality during aging. This decline in SC function...

The intricate organization of distinct cellular compartments is paramount for the maintenance of normal biological functions and the orchestration of complex biochemical reactions. These compartments, whether membrane-bound organelles or membraneless structures like Cajal bodies and RNA transport granules, play crucial roles in cellular function. Liquid-liquid phase separation (LLPS) serves as a reversible process that elucidates the genesis of membranelles structures through the self-assembly...

Studies of laminopathy-based progeria offer insights into aging-associated diseases and highlight the role of LMNA in chromatin organization. Mandibuloacral dysplasia type A (MAD) is a largely unexplored form of atypical progeria that lacks lamin A post-translational processing defects. Using iPSCs derived from a male MAD patient carrying homozygous LMNA p.R527C, premature aging phenotypes are recapitulated in multiple mesenchymal lineages, including mesenchymal stem cells (MSCs). Comparison...

Genetic factors play a significant role in determining an individual's longevity. The present study was aimed at identifying genetic variants associated with longevity in Indian population. Long living individuals (LLIs), aged 85+, were compared with younger controls, aged 18-49 years, using data from GenomegaDB, a genetic database of Indians living in India. An in-house developed custom chip, having variants associated with various cancers, cardiovascular, neurological, gastro-intestinal,...

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use...

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CONCLUSION: Among healthy, physically active older adults, ALMI and incidence of sarcopenia were not improved by treatment of daily 2000 IU vitamin D, daily 1 g omega-3s, or a simple home exercise program compared with control over 3 years.