What’s the link between aging and disease? Increasingly research results indicate that it’s a disturbed metabolism

Aging is a biological process that nobody can avoid. Ideally, growing older needs to be a time to calm down and revel in the fruits of 1's labor. However, aging also has a dark side, which is usually related to disease.

Every second, your cells perform billions of biochemical reactions that power vital functions and form a highly interconnected metabolic network. This network allows cells to grow, reproduce, and repair themselves. and his Disturbances can drive the Ageing process.

But does aging result in metabolic decline or do metabolic disorders speed up the aging process? Or each?

To answer this chicken-and-egg query, one must first understand how metabolic processes break down in old age and in disease. I’m a Scientists and researchersAnd my laboratory focuses on exploring the complex relationship between metabolism, stress, and aging. Ultimately, we hope this work will provide strategies for healthier aging and a more vital life.

Relationship between metabolism and aging

Aging is the best risk factor for many individuals in society. essentially the most common diseasesincluding diabetes, cancer, heart problems and neurodegenerative diseases. A key think about the occurrence of those health problems is the disruption of cellular and metabolic Homeostasis or balance. A disruption of homeostasis destabilizes the body's internal environment, creating imbalances that may trigger a cascade of health problems, including metabolic disorders, chronic diseases, and impaired cellular function that contribute to aging and other serious conditions.

Disturbed metabolism is related to many characteristics of aging cells, akin to shortening of telomeres, i.e. damage to the protective ends of chromosomes, and genomic instabilitythe tendency to form genetic mutations.

A disturbed metabolism can also be related to poor function Mitochondria; cellular senescence, when cells stop dividing; imbalances within the gut microbes; and the reduced ability of cells to Recognizing and reacting to different nutrients.

Neurological diseases akin to Alzheimer's are prime examples of age-related diseases with a powerful link between impaired metabolism and lack of function. For example, my research team previously discovered that in aging mice, the power of bone marrow cells to Producing, storing and using energy is suppressed as a result of increased activity of a protein that modulates inflammation. This low-energy state results in a rise in inflammation, which is exacerbated by the dependence of those aging cells on glucose as their foremost energy source.

However, experimental inhibition of this protein within the bone marrow cells of aging mice revitalizes the cells' ability to supply energy, reduces inflammation, and improves the plasticity of an area of ​​the brain accountable for memory. This finding suggests that some cognitive aging might be reversed by reprogramming the glucose metabolism of bone marrow cells to revive immune functions.

New use of medication to treat Alzheimer's

In our newly published study, my team and I a brand new connection discovered between impaired glucose metabolism and neurodegenerative diseases. This led us to search out a drug that was originally developed for cancer but could potentially be used to treat Alzheimer's disease.

We focused on a Enzyme called IDO1 which plays a vital role in step one of breaking down the amino acid tryptophan. This pathway produces a key compound called kynurenine, which drives additional energy pathways and inflammatory responses. excessive kynurenine can have harmful effectsincluding an increased risk of developing Alzheimer's disease.

We found that inhibition of IDO1 Restoration of memory and brain function in numerous preclinical models, including cell cultures and mice. To understand why, we checked out the metabolism of brain cells. The brain is one in all the most glucose-dependent tissues within the body. An inability to properly use glucose to fuel necessary brain processes can result in metabolic and cognitive decline.

High IDO1 levels reduce glucose metabolism by producing excess kynurenine. IDO1 inhibitors – originally developed to treat cancers akin to melanoma, leukemia and breast cancer – could due to this fact be repurposed to scale back kynurenine and improve brain function.

Using a spread of laboratory models, including mice and cells from Alzheimer's patients, we also found that IDO1 inhibitors Restoration of glucose metabolism in brain cells. In addition, we were capable of restore glucose metabolism in mice with amyloid and tau accumulation – abnormal proteins involved in lots of neurodegenerative diseases – by blocking IDO1. We imagine that repurposing these inhibitors might be helpful in various neurodegenerative diseases.

Promote healthier cognitive aging

The effects of neurological disorders and metabolic disorders weigh heavily on individuals, families and the economy.

While many scientists have focused on the downstream effects of those diseases, akin to treating symptoms and slowing progression, earlier treatment of those diseases may improve cognitive abilities in old age. Our findings suggest that targeting metabolism may not only slow neurological decline but additionally reverse the progression of neurodegenerative diseases akin to Alzheimer's, Parkinson's and dementia.

Discovering recent insights into the interface between stress, metabolism and aging may pave the method to healthier aging. Further research can improve our understanding of how metabolism influences stress responses and cellular balance across the life course.