How fasting protects against ageing-related diseases

*Artificial intelligence provides insights into how smoking accelerates senescence

Researchers found evidence that fasting affects circadian clocks in the liver and skeletal muscle, causing them to rewire their metabolism, which can ultimately lead to improved health and protection against aging-associated diseases.

In a University of California, Irvine, United States (U.S.)-led study, researchers found evidence that fasting affects circadian clocks in the liver and skeletal muscle, causing them to rewire their metabolism, which can ultimately lead to improved health and protection against aging-associated diseases.

The study was published recently in Cell Reports.
The circadian clock operates within the body and its organs as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. And, while food is known to influence clocks in peripheral tissues, it was unclear, until now, how the lack of food influences clock function and ultimately affects the body.

“We discovered fasting influences the circadian clock and fasting-driven cellular responses, which together work to achieve fasting-specific temporal gene regulation,” said lead author Paolo Sassone-Corsi, Donald Bren Professor of Biological Chemistry at UCI’s School of Medicine. “Skeletal muscle, for example, appears to be twice as responsive to fasting as the liver.”

The research was conducted using mice, which were subjected to 24-hour periods of fasting. While fasting, researchers noted the mice exhibited a reduction in oxygen consumption (VO2), respiratory exchange ratio (RER), and energy expenditure, all of which were completely abolished by refeeding, which parallels results observed in humans.

“The reorganization of gene regulation by fasting could prime the genome to a more permissive state to anticipate upcoming food intake and thereby drive a new rhythmic cycle of gene expression. In other words, fasting is able to essentially reprogram a variety of cellular responses. Therefore, optimal fasting in a timed manner would be strategic to positively affect cellular functions and ultimately benefiting health and protecting against aging-associated diseases.”

This study opens new avenues of investigation that could ultimately lead to the development of nutritional strategies to improve health in humans. Sassone-Corsi first showed the circadian rhythm-metabolism link some 10 years ago, identifying the metabolic pathways through which circadian proteins sense energy levels in cells.

Meanwhile, Insilico Medicine, one of the leaders in artificial intelligence for drug discovery, biomarker development, digital medicine, and aging research, announced the publication of a new collaborative research paper titled “Blood Biochemistry Analysis to Detect Smoking Status and Quantify Accelerated Aging in Smokers” in Scientific Reports.

Smoking has long been proven to negatively affect people’s overall health in multiple ways. The study by Insilico scientists set out to determine biological age differences between smokers and non-smokers, and to evaluate the impact of smoking using blood biochemistry and recent advances in artificial intelligence. By employing age-prediction models developed by supervised deep learning techniques, the study analyzed a number of biochemical markers, including measures based on glycated hemoglobin, urea, fasting glucose and ferritin.

According to study’s results, smokers demonstrated a higher aging ratio, and both male and female smokers were predicted to be twice as old as their chronological age as compared to nonsmokers. The results were carried out based on the blood profiles of 149,000 adults.Other findings suggested that deep learning analysis of routine blood tests could replace the current unreliable method of self-reporting of smoking status and evaluate the influence that other lifestyle and environmental factors have on aging.

“I am pleased to be part of the research study, which provides fascinating scientific evidence that smoking is likely to accelerate aging. Smoking is a real problem that destroys people’s health, causes premature deaths, and is often the cause of many serious diseases. We applied artificial intelligence to prove that smoking significantly increases your biological age,” said Polina Mamoshina, a senior research scientist at Insilico Medicine.

Insilico Medicine is an artificial intelligence company headquartered in Rockville, with R&D and management resources in Belgium, Russia, UK, Taiwan, and Korea sourced through hackathons and competitions. The company and its scientists are dedicated to extending human productive longevity and transforming every step of the drug discovery and drug development process through excellence in biomarker discovery, drug development, digital medicine, and ageing research.
Insilico pioneered the applications of the generative adversarial networks (GANs) and reinforcement learning for generation of novel molecular structures for the diseases with a known target and with no known targets.

In addition to working collaborations with the large pharmaceutical companies, the company is pursuing internal drug discovery programs in cancer, dermatological diseases, fibrosis, Parkinson’s Disease, Alzheimer’s Disease, ALS, diabetes, sarcopenia, and aging. Through a partnership with LifeExtension.com, the company launched a range of nutraceutical products compounded using the advanced bioinformatics techniques and deep learning approaches. It also provides a range of consumer-facing applications including Young.AI.