The highly conserved target of rapamycin (TOR) pathway plays an important role in aging across species. Previous studies have established that inhibition of the TOR complex 1 (TORC1) significantly extends lifespan in Caenorhabditiselegans. However, it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner. Here, we apply the auxin-inducible degradation tool to knock down endogenous DAF-15, the C. elegans ortholog of regulatory associated protein of TOR (Raptor), to characterize its roles in aging. Global or tissue-specific inhibition of DAF-15 during development results in various growth defects, whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan. The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors, as well as the AAK-2/AMP-activated protein kinase α catalytic subunit. Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection. These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jgg.2023.11.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multidimensional sleep health and cognitive function across adulthood.
Sleep Health
January 2025
Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ, USA; Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol Hospital, Prague, Czech Republic.
Study Objectives: Sleep is essential for proper function of the mind and body. Studies report the effect of sleep problems on cognition but focus on only a single or limited number of sleep indicators or on clinical populations (e.g.
View Article and Find Full Text PDFExercise and exerkines: Mechanisms and roles in anti-aging and disease prevention.
Exp Gerontol
January 2025
Shanghai anti-doping Laboratory, Shanghai University of Sport, Shanghai 200438, China; Department of Rheumatology and Immunology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:
Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and neurokines, act both locally and systemically to exert protective effects against the detrimental aspects of aging.
View Article and Find Full Text PDFMotor imagery does not effectively improve walking-related performance in older adults: A randomised controlled trial.
Ann Phys Rehabil Med
January 2025
Healthy Brain & Mind Research Centre (HBM), School of Behavioural and Health Sciences, Australian Catholic University, 115 Victoria Parade, Fitzroy, VIC, 3065 Australia.
Background: Inaccurate perception of one's physical abilities is potentially related to age-related declines in motor planning and can lead to changes in walking. Motor imagery training is effective at improving balance and walking in older adults, but most research has been conducted on older adults following surgery or in those with a history of falls. Deficits in motor imagery ability are associated with reduced executive function in older adults with cognitive impairment.
View Article and Find Full Text PDFIn vivo imaging markers of glymphatic dysfunction in amyotrophic lateral sclerosis: Analysis of ALPS index and choroid plexus volume.
J Neurol Sci
January 2025
Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address:
Background: The glymphatic system, essential for brain waste clearance, has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Emerging imaging markers, such as the analysis along the perivascular space (ALPS) index and choroid plexus volume (CPV), may provide insights into glymphatic function, but their relevance to ALS remains unclear.
Objective: To assess glymphatic dysfunction in ALS patients using the ALPS index and CPV.
Cognitive function differs across healthy lifestyle behavior profiles: a 10-year population-based prospective cohort study.
J Nutr Health Aging
January 2025
Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Electronic address:
Background: Modifiable lifestyle behaviors significantly influence the risk of cognitive impairment. However, the cumulative effects of multidimensional lifestyle profiles on cognitive function remain poorly understood, as most studies examine individual lifestyle behaviors in isolation. This study aimed to identify distinct profiles of individuals based on healthy lifestyle behaviors and to examine associations between these profiles and cognitive function in older Chinese adults.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!