Valid information is power – Empower Pakistani Nurses
Search This Blog
How Fasting Activates Cellular Renewal: The Body's Internal Spring Cleaning
The practice of fasting, abstaining from some or all food and drink for a set period, has gained significant traction in recent years, fueled by claims of various health benefits. Beyond weight management, proponents suggest that fasting can enhance longevity, protect against neurodegenerative diseases, and even play a role in cancer prevention. At the heart of these potential benefits lies a fundamental cellular process known as autophagy, the body's intricate system for self-cleaning and recycling 1. This report delves into the fascinating connection between fasting and autophagy, exploring the molecular mechanisms that initiate this cellular renewal, the specific processes involved, and the compelling research linking it to various aspects of health and disease 1.
The Spark of Self-Eating: How Fasting Initiates Autophagy at the Molecular Level
The initiation of autophagy during fasting is a direct consequence of the cell's response to a reduction in available nutrients 2. When the body is deprived of food, particularly glucose and amino acids, intracellular nutrient levels decline 2. This scarcity acts as a stress signal, prompting the cell to seek alternative energy sources and to recycle existing cellular components to maintain function 9. The cellular response to this nutritional challenge is not a passive decline but rather an active reprogramming aimed at self-preservation, revealing a sophisticated internal monitoring system that constantly assesses the availability of essential resources.
Central to this process are two key signaling pathways, involving the enzymes AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which act as crucial nutrient sensors within the cell 1. Under conditions where nutrients are abundant, mTOR is active and functions to promote cell growth and inhibit autophagy 1. However, during fasting, the levels of adenosine triphosphate (ATP), the cell's primary energy currency, decrease, while the levels of adenosine monophosphate (AMP) increase 1. This shift in the AMP/ATP ratio activates AMPK 1. Activated AMPK plays a dual role: it inhibits mTOR and directly promotes autophagy by phosphorylating key autophagy-related proteins, such as Unc-51-like autophagy activating kinase-1 (ULK1) 1. Bujak et al.'s 2017 study highlighted the essential requirement for skeletal muscle AMPK in initiating autophagy during prolonged fasting, which in turn is crucial for maintaining blood glucose levels 33. AMPK, therefore, functions as a master metabolic switch, activating energy-producing catabolic pathways like autophagy when cellular energy is low, while simultaneously suppressing energy-consuming anabolic pathways like protein synthesis regulated by mTOR. This coordinated action underscores the cell's remarkable efficiency in managing its energy resources.
To better understand this intricate molecular dance, several analogies can be employed. Autophagy can be likened to a "housekeeper" diligently cleaning up cellular debris, removing old and damaged components 30. Another useful comparison is that of a "city's recycling and waste management system," where autophagy identifies and disposes of cellular waste, recycling useful materials back into the system 30. In times of resource scarcity, autophagy acts as a "self-eating survival mechanism," allowing the cell to break down non-essential parts to generate energy 30. Finally, the process can be visualized as a "trash bag (autophagosome) and compost (lysosome)" system, where damaged cellular material is collected and then broken down for reuse 31. These analogies help to make the complex molecular processes more accessible and relatable to a general audience.
Inside the Cellular Recycling Plant: The Step-by-Step Processes of Autophagy
Autophagy is a highly organized process that unfolds in a series of distinct steps within the cell. The process begins with initiation, where the stage is set for autophagy to occur 5. This involves the formation of the phagophore assembly site (PAS), a specific location within the cell where the autophagosome will begin to form 5. The ULK1 complex, a key protein complex, plays a crucial role in initiating membrane nucleation at the PAS 1. Additionally, the Class III phosphatidylinositol 3-kinase (PI3K) complex, which includes the protein Beclin-1, is involved in the initial steps of vesicle isolation 1. The fact that autophagy initiates at specific cellular locations highlights the highly organized nature of this process.
Following initiation, the process moves to phagophore formation, where the isolation membrane, or phagophore, begins to elongate and expand 1. This membrane eventually engulfs the cellular components destined for degradation, forming a double-layered vesicle known as the autophagosome 1. Numerous autophagy-related (ATG) proteins are involved in this stage, orchestrating the growth and shaping of the autophagosome 1. Two ubiquitin-like conjugation systems, involving the proteins Atg12-Atg5 and LC3 (Atg8), are essential for this membrane expansion and maturation 1. The formation of the autophagosome is a dynamic process, requiring the precise coordination of multiple proteins acting in a manner akin to a cellular assembly line.
In the autophagosome maturation phase, the double-membraned vesicle fully encloses its cargo, which can include a variety of cytoplasmic components such as damaged organelles, misfolded proteins, and even invading pathogens 1. Autophagy can be selective, targeting specific types of cellular waste through specialized forms like mitophagy (for mitochondria) and xenophagy (for pathogens) 1. Autophagy receptors, such as the protein p62, play a role in recognizing and targeting specific cargo, particularly ubiquitinated proteins, for engulfment by the autophagosome 4. This selectivity underscores that autophagy is not merely a general disposal system but a precise mechanism for maintaining cellular health.
The final stage involves lysosomal fusion, where the mature autophagosome fuses with a lysosome, an organelle containing powerful digestive enzymes 1. This fusion creates a new compartment called the autolysosome, where the lysosomal enzymes degrade the engulfed cellular cargo 1. The breakdown products, such as amino acids and lipids, are then recycled back into the cytoplasm to be used by the cell for building new molecules and generating energy 1. This process of degradation and recycling highlights the cell's remarkable efficiency in utilizing its resources, especially during times of stress or nutrient deprivation.
The process of autophagy presents several visually interesting aspects. The formation of the double-membrane autophagosomes can be directly observed using electron microscopy 17. Furthermore, researchers often use fluorescently tagged proteins, such as GFP-tagged LC3, to track the formation and movement of autophagosomes within cells, appearing as punctate dots under a microscope 33. More advanced techniques employing multiple fluorescent proteins, like GFP and RFP, allow scientists to monitor the entire process of autophagy, from autophagosome formation to fusion with lysosomes, providing a dynamic view of this cellular recycling pathway 31.
Extending the Years: The Link Between Fasting-Induced Autophagy and Longevity
A growing body of research suggests a compelling link between fasting-induced autophagy and the extension of lifespan. Studies across various animal models, from simple organisms to mammals, have shown that interventions that increase autophagy are often associated with increased longevity 1. For instance, research has indicated that autophagy is essential for the lifespan-extending effects of calorie restriction, reduced insulin/IGF-1 signaling, and treatment with the drug rapamycin 10. A notable example is the nematode worm C. elegans, where mutations in the daf-2 gene, which reduces insulin/IGF-1 signaling, lead to both increased autophagy and a longer lifespan, and this longevity is dependent on functional autophagy genes 32. Furthermore, studies in animal models of aging have demonstrated that fasting-induced autophagy can improve cardiac function and extend lifespan 1. The consistency of this link across diverse species suggests that autophagy plays a fundamental role in the aging process by clearing damaged cellular components that accumulate over time.
While direct evidence of fasting-induced autophagy extending human lifespan is still an area of active investigation, emerging research in humans provides promising insights. Studies have shown that intermittent fasting can improve various physiological and molecular markers associated with aging 1. For example, alternate-day fasting has been observed to improve markers of aging in healthy individuals 9. Autophagy's role in removing age-associated damaged organelles and proteins is believed to be a key contributor to these beneficial effects 10. Professor Guido Kroemer, a prominent researcher in the field, has extensively studied the positive role of autophagy in increasing lifespan by facilitating the removal of oxidative damage and dysfunctional cellular components 46. The Nobel Prize-winning work of Yoshinori Ohsumi on the mechanisms of autophagy has been foundational in understanding its importance in cellular health and its potential link to longevity 20. While more long-term human studies are needed, the current evidence strongly suggests that enhancing autophagy through fasting holds promise for promoting healthy aging in humans.
Animal Model
Intervention
Effect on Autophagy
Effect on Lifespan
Key Researchers/Findings
C. elegans
daf-2 mutation
Increased
Increased
Melendez et al., 2003
- Autophagy essential for daf-2
longevity
Yeast, Worms, Flies,
Mice
Spermidine
Increased
Increased
Eisenberg et al.,
2009, 2016 - Spermidine extends lifespan via autophagy induction
C. elegans
Dietary Restriction
Increased
Increased
Lifespan extension
abolished by autophagy gene inactivation
Yeast, Worms, Flies
Rapamycin
Increased
Increased
Lifespan extension
often requires autophagy
C. elegans
Germline Removal
Increased
Increased
Autophagy genes
crucial for longevity
Various
Reduced Mitochondrial
Respiration
Increased
Increased
Inhibiting autophagy
shortens lifespan in mitochondrial mutants with typical longevity
Protecting the Mind: Autophagy's Role in Neurodegenerative Diseases, Particularly Alzheimer's
Neurodegenerative diseases, such as Alzheimer's, are characterized by the accumulation of misfolded proteins, like amyloid-beta and tau, which disrupt normal neuronal function 10. Autophagy plays a critical role in maintaining the health of neurons by degrading these aggregate-prone proteins and ensuring overall protein homeostasis 10. Impairment of the autophagy pathway is increasingly recognized as a contributing factor to the pathology of various neurodegenerative conditions 6. Given that neurons are largely non-dividing cells, they are particularly reliant on efficient autophagy to clear out toxic protein aggregates that cannot be diluted through cell division.
Research in animal models suggests that fasting may have a beneficial impact on cognitive decline associated with aging and Alzheimer's disease 39. For instance, studies have shown that time-restricted feeding in mouse models of Alzheimer's can improve cognition and reduce the accumulation of amyloid in the brain 42. The potential mechanisms behind these effects may involve the enhancement of autophagy, which could aid in the clearance of amyloid-beta and tau, the hallmark protein aggregates of Alzheimer's 15. Interestingly, some studies have observed an increased number of autophagic vacuoles in the brains of Alzheimer's patients, which might indicate a problem with the later stages of autophagy, such as the fusion of autophagosomes with lysosomes, rather than an issue with the initial induction of autophagy 13. Research on autophagy enhancers, like rapamycin, has shown that they can increase the fusion of autophagosomes with lysosomes in laboratory settings 13. While these findings are promising, further investigation is needed to fully understand the precise mechanisms and the effectiveness of fasting-induced autophagy in combating Alzheimer's pathology in humans. Animal studies suggest that even short-term fasting could promote neuronal autophagy, offering a simple and potentially therapeutic approach for neurodegenerative conditions 17.
Fasting Method
Animal Model
Tissue/Sample Evaluated
Molecular Mechanism Observed
Key Findings
Fasting-Mimicking Diet
(FMD)
E4FAD and 3xTg mice
(Alzheimer's models)
Hippocampus
phosphorylated
(p)-tau/tau, microglia level and activation, AT8+, and ionised calcium
binding adaptor molecule 1+↓; neurogenesis, and memory↑ 40
Improved memory 40
16 h fasting/day
Sprague–Dawley rats
with osteoarthritis (Alzheimer's model)
Serum and joint
histology
Tumour necrosis factor
(TNF)-α and interleukin (IL)-1β↓; memory↑ 40
A Potential Shield: Fasting-Induced Autophagy and Cancer Prevention – Navigating the Evidence
The relationship between fasting-induced autophagy and cancer prevention is complex and still under investigation. Autophagy appears to play a dual role in cancer 22. In the early stages of tumorigenesis, it can act as a tumor suppressor by removing damaged cells, reducing oxidative stress, regulating cell growth, and preventing uncontrolled cell proliferation 22. Tumor suppressor genes often stimulate autophagy, further suggesting this protective role 28. However, in established tumors, autophagy can paradoxically promote cancer cell survival by helping them withstand stressful conditions like nutrient deprivation and therapeutic interventions 22. This context-dependent nature of autophagy in cancer is crucial to consider.
Emerging evidence suggests that intermittent fasting and fasting-mimicking diets might have a role in both cancer prevention and treatment 21. Some studies indicate that fasting can enhance the effectiveness of chemotherapy and immunotherapy while reducing side effects 23. It has been proposed that fasting might make cancer cells more vulnerable to treatment by targeting their metabolic vulnerabilities 21. Preclinical studies have shown that short-term fasting can enhance the efficacy of chemotherapeutic drugs in treating various types of malignancies 24. Additionally, fasting has been shown to reduce levels of insulin growth factor (IGF-1), a marker associated with increased cancer risk 21. While these findings from preclinical studies are promising, the evidence for cancer prevention in humans through fasting-induced autophagy is still limited and requires careful interpretation 19. More robust human clinical trials are needed to confirm these potential benefits. The seemingly contradictory roles of autophagy in cancer, acting as both a suppressor and a promoter, along with the idea that fasting might selectively target cancer cells, are surprising findings that warrant further research and could be of great interest to a wider audience.
Podcast Gold: Compelling Narratives, Surprising Facts, and Interesting Research Findings
Several compelling narratives, surprising facts, and interesting research findings related to fasting and autophagy could be woven into a viral podcast episode. The story of Yoshinori Ohsumi's Nobel Prize for his groundbreaking work on autophagy in yeast and its profound implications for understanding human health and disease is a captivating tale of scientific discovery 20. The very term "autophagy," meaning "self-eating" in Greek, is an intriguing fact that can immediately pique listener interest 7. The existence of different specialized forms of autophagy, such as mitophagy for clearing damaged mitochondria and xenophagy for eliminating pathogens, highlights the sophisticated nature of this cellular process 7. The observation that autophagy tends to decline with age suggests a potential link to the aging process itself 1. Furthermore, the finding from human studies that prolonged nightly fasting might be associated with a lower risk of breast cancer recurrence offers a tangible and potentially actionable piece of information 23. The overarching idea that simple lifestyle interventions like fasting can tap into our body's innate cellular renewal system to potentially impact major health concerns like aging, Alzheimer's disease, and cancer is a powerful and motivating message. The concept of "autophagic flux," representing the efficiency of this cellular cleaning process, provides a framework for understanding overall cellular health 31.
Conclusion:
The Promise of Autophagy – From Molecular Mechanisms to Health Implications
In summary, fasting triggers autophagy through a well-defined molecular mechanism involving the activation of AMPK and the inhibition of mTOR 1. This process unfolds in a series of carefully orchestrated stages, including initiation, phagophore formation, autophagosome maturation, and lysosomal fusion 1. The link between autophagy and longevity is strongly supported by animal studies, with emerging evidence suggesting similar benefits in humans 1. Autophagy plays a crucial role in clearing misfolded proteins associated with neurodegenerative diseases like Alzheimer's, and fasting shows promise in mitigating Alzheimer's pathology in animal models 10. Regarding cancer prevention, while preclinical studies are encouraging and suggest a complex, context-dependent role for autophagy, the evidence in humans remains limited and requires further rigorous investigation 21. Future research should focus on identifying optimal fasting protocols for specific health outcomes and understanding individual variations in the autophagy response. It is important to approach the topic of fasting for health benefits, especially in the context of cancer prevention, with caution and to consult with healthcare professionals before making significant dietary changes.
35.Nutrient Deprivation Induces Neuronal
Autophagy and Implicates Reduced Insulin Signaling in Neuroprotective Autophagy
Activation - PMC - PubMed Central, accessed on March 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2629092/
36.Full article: Cellular adaptation to
nutrient deprivation: crosstalk between the mTORC1 and eIF2α signaling pathways
and implications for autophagy - Taylor & Francis Online, accessed on March
30, 2025, https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1056947
The Pakistan Nursing & Midwifery Council (PNMC) has introduced a new uniform dress code for nurses working in clinical settings across the country. The announcement, in an official letter from the PNMC dated January 31, 2024, stated guidance about professional attire of nursing staff in Pakistan. The new dress code approved during the 6th session of the council held from January 15-17, 2024, under the leadership of Ms. Farzana Zulfiger, President of PNMC, specifies new uniforms for male and female nurses. Female nurses are to wear a dark blue shalwar kameez with a nameplate, accompanied by a white coat and a blue scarf/dupatta. Male nurses are required to wear dark blue scrubs along with a nameplate. Category Uniform Female Nurses Dark blue shalwar kameez with nameplate, white coat or blue scarf/dupatta Male Nurses Dark blue scrubs with nameplate Health Departments across Punjab, Sindh, Balochistan, Khyber P...
Are you confused about the terms BSN, BScN, Generic BSN, Post-RN, BS Nursing, and BSc Nursing? We receive many questions about these terms at PKN. This updated post will clarify these terms, especially in the context of recent changes in Pakistan. In short, the Generic BSN is a degree program for individuals who wish to join the nursing profession after 12 years of schooling, while the Post-RN BScN is a degree program for nurses who already have a three-year diploma in nursing. Generic BSN The Generic BSN is an ideal option for those who want to enter the nursing profession in Pakistan. Previously, another option to join the nursing profession was the 3-year diploma in general nursing. However, according to the Higher Education Commission (HEC) of Pakistan's policies, the diploma in nursing was phased out across Pakistan in 2018. The Generic BSN is a 4-year degree program followed by a one-year internship. An internship involves practical nursing practice in a hospital u...
1. Introduction: Prolonged bottle feeding, defined as the continued use of a feeding bottle beyond the age of two years, is a practice that extends beyond the generally recommended weaning period of 12 to 18 months by pediatric guidelines 1 . While bottle feeding offers convenience, comfort, and a means to ensure adequate nourishment for infants and young toddlers 1 , its extended use into the preschool years carries several unintended negative consequences for a child's overall health and development 1 . Understanding these potential risks is crucial for parents and caregivers to make informed decisions regarding the appropriate duration of bottle feeding and to facilitate a timely transition to cup drinking 1 . This report will explore the physical, mental and emotional, and dental health implications associated with prolonged bottle feeding, delving into the underlying mechanisms and highlighting the recommendations provided by leading pediatric health organizations. The relian...
The Pakistan Nursing Council ( now called the Pakistan Nursing and Midwifery Council or PN&MC ) has introduced internship guidelines 2021 for undergraduate nursing students who have completed four years of college. The internship program must be completed in a PNC recognized hospital, which will offer PNC-specified clinical experiences. During this program, students will have a combination of practical and theoretical experiences that will enable them to acquire competency and experience to perform as an independent nurse. Successful completion of the internship period will result in an internship certificate, and students will be eligible to appear in the licensing examination. Below are some frequently asked questions and answers from these guidelines. What is the nursing internship program in Pakistan? The nursing internship program is a one-year program for nursing students in Pakistan, which is taken after the successful completion of a four-year undergraduate...
Courtesy: Sabir Mehno PIMS I solemnly pledge myself before God and in the presence of this assembly to pass my life in purity and to practise my profession faithfully. I shall abstain from whatever is deleterious and mischievous, and shall not take or knowingly administer any harmful drug. I shall do all in my power to maintain and elevate the standard of my profession and will hold in confidence all personal matters committed to my keeping and all family affairs coming to my knowledge in the practice of my calling.
Standard Operating Procedures (SOPs) for Managing Nurses’ Duty Roster Version 3 (January 2019) Developed By: Khalil Ahmed Head Nurse, CCU, IH, PIMS, Islamabad Description: The purpose of developing these SOPs was to create uniformity and clarity in the policies regarding nurses’ duty roster. This document has brought the already practised rule into written form. The first version of the SOPs was introduced in Emergency and Accident Center, PIMS in 2014. Further improvements have been brought in the subsequent versions. Constructive feedback would be appreciated. A sample duty roster which incorporates some of these rules is attached. SOPs Rationales 1. Days off available in a month: 1.1. Weekly off: A nurse will be eligible to avail weekly days off equal to the number of Sundays in a month. Because every Sunday is an official day off, therefore, all nurses are eli...
1. Download challan form from the downloads section of online.pnc.org.pk . The exact link of challan form is: http://online.pnc.org.pk/RevisedChallan.pdf 2. Submit fee in any Habib Bank branch and get it stamped from the bank. 3. Scan the challan copy and upload it online Note: you can easily scan challan form using your cellphone which has more than 5 megapixels camera. You can use CamScanner app to scan challan form. link: https://play.google.com/store/apps/details?id=com.intsig.camscanner
The Pakistan Nursing Council (PNC), ( now called the Pakistan Nursing and Midwifery Council or PNMC ) is the regulatory body for nursing education and practice in Pakistan. PN&MC notified the eligibility criteria for the appointment of faculty members in nursing colleges. The PNMC's notification, which was issued in August 2015 (vide letter number F-11-PNC-admin/2015-723), outlines the minimum qualifications, experience, and publications required for nursing lecturers, assistant professors, associate professors, and professors. In this blog post, we will discuss the eligibility criteria in detail and answer some common questions about them. Q: What are the minimum qualifications required for a Nursing Lecturer position in a college of nursing according to PNMC? A: The minimum qualifications required for a Nursing Lecturer position in a college of nursing are: Registered Nurse and Registered Midwife with Post RN BSN degree (Two years of post-degree experience, prefe...
Understanding the nurse-patient ratio according to the Pakistan Nursing Council (PNC) is crucial for ensuring proper healthcare standards in hospitals across the country. However, it is important to acknowledge that nurse-patient ratios in many hospitals in Pakistan are currently far lower than the recommended guidelines. In this blog post, we will provide a detailed analysis and breakdown of the official PNC notification on this subject. The official PNC notification on this subject is given below. Official Nurse-Patient Ratio According to Pakistan Nursing Council: The PNC issued a notification (No. PNC F-7-14-Admin/2021/ 3702) on 25th May 2021, outlining the minimum nurse-to-patient ratio for hospitals across Pakistan. The guidelines provided in this notification are as follows: General Hospital Units: In general hospital units, the nurse-to-patient ratio should be 1:3 beds, which means three nurses for every ten beds, with one reliever nurse for e...
Comments
Post a Comment
Give your Comments here... اپنی رائے کا اظہار یہاں کریں۔۔۔۔۔۔۔۔۔۔۔۔۔۔۔۔۔۔۔