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
