More good news from a summary in a new medical textbook. Read the last line of the Abstract below:
Autophagy as a Promising Therapeutic Target in Age-Associated Neurodegenerative Disorders
Aging, and the reason for the process, has been an area of research where strides can improve the healthspan and lifespan of people all over the globe. Cellular senescence and cell death due to oxidative stress-mediated damage to macromolecules are the major reasons for aging as a process but certain factors increase and decrease the rate of aging. The process of autophagy contributes to the decrease of the rate of aging and also alleviates and prevents the symptoms of aging-induced neurodegenerative diseases. Therefore, targeting autophagy process and increasing its frequency can improve the pathologies of many age-associated neurodegenerative disorders; especially Alzheimer’s disease (AD) and Parkinson’s disease (PD). Practices like intermittent fasting and caloric restriction have shown to increase the rate of autophagy and, in turn, have shown promising results as therapeutic interventions in AD and PD. Administration of caloric restriction mimetics like spermidine, rapamycin, metformin, and fisetin have shown to improve cognitive functioning in AD and PD through autophagy activation.
Aging and death remain a great mystery of biological science. Many processes associated with aging have been described. In general, the aging process is associated with inflammation. Inflammation is the cellular and vascular response of tissues to infection and tissue damage. Under normal conditions, it provides tissue healing with a controlled humoral and cellular response and prevents the development of infection. The presence of chronic, low-level inflammation without significant infection was termed “inflammaging.” The use of methods aimed at regulating or preventing inflammaging will prevent, at least reduce or delay the effects of both the prevention of symptoms that can occur with aging and the emergence of diseases that can be seen. The use of treatments and methods to regulate inflammation in the early period when signs of aging begin to appear will have a positive effect on aging by activating the body’s compensatory mechanism. Aging is strongly affected by metabolism. Research on drugs such as polyphenolic compounds, statins, and aspirin will increasingly continue, as they can delay the aging process, prolong lifespan, and reduce age-related degeneration and associated morbidity and mortality by targeting mTOR, NF-κβ, inflammatory cytokines, and related signal transduction pathways. Research on polyphenolic compounds, anti-aging pharmacologic agents will increasingly continue, as they can delay the aging process, prolong life, and reduce age-related degeneration and associated morbidity and mortality by targeting mTOR, NF-κb, inflammatory cytokines, and related signal transduction pathways.
It’s a good question as to whether inflammaging is just a dysfunctional overly-activated inflammation process, or if high (but otherwise normal) inflammation is a result of higher tissue damage with age. It could be a vicious cycle of both. Fortunately, rapamycin partially alleviates both parts by tamping down the immune system and reducing oxidative damage.
I’d note if one has access to the book…it’s not really a “medical” textbook. It’s more of a biochemistry of aging “textbook”.
The source of citations in this book chapter for metformin are 3 genetically modified mice studies around 2015-2017. These are not human studies. So it’s important to keep in mind that most of the book is mainly a review of mice studies and an overview of the biochemical mechanisms proposed.
Meanwhile, we have human studies showing mixed effects of metformin for AD - mostly tending towards nothing and sometimes negative. Some people actually do worse on metformin - especially APOE4.