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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...

The acidic pH of lysosomes required for function is established by the electrogenic V-ATPase proton pump. How lysosomes prevent hyper-acidification by the pump is not well established. Recently, the Parkinson's disease (PD)-associated protein TMEM175 was proposed as a H+-selective channel to leak protons to counter over-acidification. We rigorously address key findings and predictions of this model and show that, in the lysosome, TMEM175 predominantly conducts K+ and is not a H+-selective...

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.

No abstract

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.