Aging & Longevity

Population aging is accelerating, yet the multi-organ aging process and the geroprotective effects of dietary protein restriction (PR) remain poorly understood. Here, we conducted comprehensive proteomic analyses on 41 mouse tissues during male mouse aging and PR. Our findings identified tissue-specific aging hallmarks, including widespread changes in immunoglobulins and serine protease inhibitors across multiple tissues. PR mitigated age-related tissue-specific protein expression, epigenomic...

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Cross-education (CE), the phenomenon whereby unilateral strength training induces neuromuscular adaptations in the contralateral limb, is underpinned by distributed cortical and subcortical plasticity. This study evaluated acute neural responses to a single bout of metronome-paced unilateral strength training in younger (n = 17; 27 ± 6 years) and older adults (n = 18; 67 ± 5 years). Neurophysiological assessments included corticospinal excitability and inhibition via transcranial magnetic...

ObjectiveThis study evaluated the effectiveness of a novel multidimensional group intervention aimed at enhancing subjective cognitive and psychosocial functioning in community-dwelling older adults.MethodsSixty cognitively healthy adults aged 65-75 were randomly assigned to an experimental or control group. The 10-week intervention integrated five components: memory compensation, problem solving, emotion regulation, mindfulness, and locus of control. Validated self-report measures were...

Aging is a multifaceted process involving cellular senescence and a significant remodeling of the immune network driven by the senescence-associated secretory phenotype (SASP). This progressive process needs adaptable drivers to push it forward. The redox-sensitive high mobility group box 1 (HMGB1) protein is a perfect example of this kind of oxidative stress- and aging-related multifunctional protein. The HMGB1 protein is an important non-histone DNA chaperone which maintains chromatin...

Cellular senescence is a state where cells permanently exit the cell cycle after a finite number of divisions, while maintaining metabolic activity. This phenomenon, initially described by Leonard Hayflick, plays a pivotal role in aging, contributing to the progressive decline in physiological function by promoting tissue dysfunction and restricting regenerative capacity. It is regulated by an array of factors, including DNA damage, telomere shortening, oxidative stress, mitochondrial...

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily marked by the degeneration of dopaminergic neurons and pathological α-synuclein (α-syn) accumulation. Although insulin-degrading enzyme (IDE) has been implicated in both type 2 diabetes mellitus and amyloid-protein clearance, its precise relevance to PD pathogenesis remains unclear. In this study, we show that IDE expression is reduced in the nigrostriatal region of aging homozygous A53T α-syn mice and in...

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a...

Age-related thymic involution increases vulnerability to cancers and infection in older adults, yet the driving mechanisms and its impact on peripheral T cells remain unclear. Using single-cell sequencing, we here analyzed 387,762 cells from human thymus and peripheral blood of young and aged individuals. Within thymus, we found aging reduced T-lineage potential in early thymic progenitors but increased innate lymphocyte lineage potential. Aged thymus were enriched in mature T cells with low...

CONCLUSIONS: Older age, gender, and chronic diseases play pivotal roles in frailty transitions, with heart disease identified as an important factor for frailty improvement in both genders. Early frailty screening and sex-sensitive approaches may help mitigate frailty progression among community-dwelling older adults.

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With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (D(f)) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of D(f) on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1. We...

Epigenetic inheritance alerts naïve descendants to prepare for stresses that could still be present, whereas distant descendants return to a basal state after several generations without stress. However, organisms are frequently exposed to stresses successively across generations. We found that parental hypoxia exposure increased P0 longevity, caused intergenerational lipid reduction, and elicited transgenerational fertility reduction that was dependent on generationally transmitted small RNAs....

Many elements of an organism's behavior are intertwined with the organism's health. Over a long period of time, health status is also indicative of life span, with improved health correlating with a longer life. However, the relationship between longevity and behavior remains relatively unexplored. Here, we report that modification of a single longevity gene downstream of dietary restriction and hypoxia markedly alters behavior in Caenorhabditis elegans. We found that modified expression of...

Aging is characterized by disruptions in metabolic homeostasis, yet the mechanisms that regulate these metabolic changes remain poorly understood. We show that the serine/threonine-protein phosphatase 6 (PP6) regulatory subunit 3, SAPS3, is a critical regulator of metabolism during aging. SAPS3 deletion significantly extends lifespan in mice and counteracts age-related impairments in metabolic health. SAPS3 deficiency improves the effects of aging on the affective behaviors, cognition, and motor...

Senescence is a multifactorial and individualised process of age-related physiological decline. Cellular markers, such as telomere length and DNA methylation, can reveal subtle changes associated with chronological age or expected lifespan. In this study, we evaluated the utility of fin tissue as a surrogate for assessing telomere length and proportion of DNA methylation in the gonads of a small, short-lived laboratory fish, the turquoise killifish (Nothobranchius furzeri). We collected fin and...

CONCLUSIONS: This study supports incorporating RHGS assessment into routine midlife health screenings and adopting sex- and age-specific strategies to improve cost-effective disease prevention. Clinically, prioritize cognitive screening in older adults with low RHGS, focus on glucose and lipid disorders in middle-aged individuals with low RHGS, and emphasize cardiovascular risk assessment in middle-aged and older females with low RHGS.

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Investigating the interplay between mitochondrial DNA (mtDNA) variations and epigenetic aging metrics may elucidate biological mechanisms associated with age-related diseases. We estimated epigenetic age acceleration (EAA) metrics from DNA methylation data and derived mtDNA metrics, including heteroplasmic variants and mtDNA copy number (mtDNA CN) from whole genome sequencing. Linear regressions and meta-analyses were conducted to assess associations between EAA and mtDNA metrics, adjusting for...

CONCLUSION: The quantitative value of SCV was negatively correlated with cognitive decline. Daily tea consumption may have a positive impact on the quantitative features of SCVs in the young group. As SCVs are a component of the glymphatic system, their blood flow may affect the clearance of toxic proteins.