Join the club for FREE to access the whole archive and other member benefits.

Reason reviews progress in longevity research and treatments from 2021

There is a phenomenal amount of work going on across the spectrum of ageing - something is going to work eventually!

31-Dec-2021

Key points from article :

Advocacy for Aging Research
 - Treating aging as a medical condition is no longer the fringe idea it once was
 - too many people are talking about only modest gains rather than the goal of radical life extension
 - popular media continues to do a terrible job in explaining
 - there is a strong economic argument for major investment in aging research and the development of therapies
Longevity Industry
 - Investment in the industry is certainly growing
 - Kizoo, Apollo Ventures and Korify Capita launched funds
 - number of biotech startups is growing in Europe and US 
 - some intend to target only skin aging to use the less costly cosmetics regulatory pathway
The Community
 - Methuselah Foundation finds itself with more resources than it can easily access or spend (hundreds of millions of dollars due to cryptocurrency)
 - Lifespan.io has extended its crowdfunding efforts to running small human trials of simple therapies, starting with mTOR inhibitors
 - Forever Healthy Foundation continues to turn out great analyses of available therapies
 - Astera Institute's Rejuvenome project launched a sizable philanthropic effort to perform useful life span studies in mice 
  - Radical Life Extension Group are performing small human trials of simple potential therapies such as plasma dilution
Senolytics and Other Senotherapeutics
 - models of aging based solely on senescent cell accumulation produce decent predictions
 - approaches include selective destruction of senescent cells, suppression of their activities, or prevention of senescence
 - senescent cells are likely different by tissue, and early drugs variably effective by tissue
 - continual clearance of senescent cells, as opposed to intermittent clearance, is probably a bad idea
 - early life use of senolytics may also be harmful over the long term
 - little progress has been made on cheap, simple ways to assess the burden of senescent cells
 - NIH has launched SenNet, a major research initiative in the biochemistry of cellular senescence
Inflammation and Other Immune Aging
 - adaptive immune system ages in its own way distinct from the aging of the innate immune system
 - researchers see CD4+/CD8+ cell ratio as a useful biomarker of immune aging
 - every aspect of immune aging should be a high priority target for intervention
 - regrowth of the thymus is an important goal - Rac1 inhibition is a possible target
 - changes in hematopoiesis, and damage to hematopoietic stem cell populations, are critical parts of immune aging
Regenerative Medicine
 - working towards ways to produce universal cells that can be introduced safely into any patient
 - cell reprogramming is being combined with prior scaffold techniques to produce muscle tissue regeneration
 - stem cell therapy improves mitochondrial quality control
 - first generation mesenchymal stem cell (MSC) therapies suppress age-related inflammation
 - exosome treatments (rather than the delivery of stem cells themselves) have been showed to work in animal models
Cardiovascular Aging
 - reversal of atherosclerotic plaques achieved in mice by targeting antioxidants to the cell lysosome to clear oxidized LDL
 - earlier research indicating that nattokinase supplementation can reverse plaque was not replicated in a more rigorous trial
 - autophagy is protective in heart aging
The Human Microbiome
 - gut microbiome becomes uniquely dysfunctional over the course of aging
 - no one universal beneficial configuration of the microbiome
 - aging gut microbiome may contribute to age-related anabolic resistance and immune system dysfunction
 - age-related decline of immune system allows for pathological microbes to grow in number
 - fecal microbiota transplantation may be a simple approach to restore a youthful microbiome
 - intermittent fasting helps to beneficially alter the gut microbiome
Mitochondrial Aging
 - evidence that mitochondrial aging contributes to sarcopenia, Alzheimer's disease, atrial fibrillation and immunosenescence
 - much of mitochondrial dysfunction with age may stem from a loss of mitophagy
 - variety of approaches to improving mitochondrial function, including mitochondrial transplantation 
Cancer
 - most promising path to a universal cancer therapy is interference in telomere lengthening
 - CAR-T immunotherapies are performing well in comparison to prior generation of chemotherapies and radiotherapies
 - researchers are now adding chimeric antigen receptors to immune cells other than T cells
 - cancer survivors' shortened life expectancy may be due to an increased burden of cellular senescence from cell-killing therapies
Neurodegeneration and Damage to the Brain
- lots of interesting correlations in aging and neurodegeneration
 - remains unclear as to whether causation is involved, or an underlying cause of aging producing multiple pathologies
 - amyloid may contribute to reduction in capillary density - effectively a hallmark of aging
 - lymphatic system of the brain is a new point of focus in AD
 - evidence points to microglial dysfunction in the development of neurodegenerative conditions
 - assays for the early stages of neurodegenerative conditions will likely soon improve greatly
Other Age-Related Molecular Waste
 - there are numerous other sorts of amyloid in the aging body
 - transthyretin amyloidosis contributes to numerous issues in aging
Epigenetics and Cellular Reprogramming
 - rise of partial reprogramming as a way to reset epigenetic changes characteristic of aging
 - reprogramming is the adaptation of the process that naturally takes place during embryogenesis
 - can the epigenetic reset can be separated from dedifferentiation into stem cells?
 - introducing developmental signaling into adults in order to spur greater regeneration is still at an early stage
 - number of different epigenetic clocks expanding rapidly
 - need to validate and understand the clocks that exist
 - GrimAge clock continues to produce good results
Fasting and Calorie Restriction
 - short term fasting can improve numerous measures of immune function
 - some work underway to directly compare the results of intermittent fasting versus calorie restriction in humans
 - calorie restriction slows cognitive decline, muscle atrophy, and lowers blood pressure and cardiovascular disease risk
 - calorie restriction mimetic compounds assessed to date compare poorly to the practice of calorie restriction
Parabiosis and Plasma Dilution
 - plasma dilution emerged from parabiosis studies and is being tested in formal and informal trials
 - evidence to suggest that it is actually the albumin, provided when blood is diluted, that is beneficial
 -  transfusions from fit mice to sedentary mice produce benefits to health, in large part mediated by clusterin level
Odds and Ends
 - 95% of present centenarians are frail: rejuvenation therapies are much needed
 - historical gains in life expectancy were not just a matter of reduced child mortality, but occurred at all ages
 - only a subset of cells in visceral fat are responsible for the harms that it causes to health and metabolism
 - ability of fullerenes to extend life in mammals has quite comprehensively failed to be replicated
 - ENH1 inhibition allows scarless healing of skin injuries in mice
 - disruption of elastin structures in skin is a big problem, as there is no good approach queued up at an advanced stage of research
 - most small molecules shown to slow aging change the expression of extracellular matrix genes
 - VEFG gene therapy slows the loss of capillary density and extends life in mice
 - continued progress towards reversible cryopreservation of organs
Topics mentioned on this page:
Life Extension, Ageing Research