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Reason reviews progress in longevity research and treatments from 2021

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 from person to person over the course of aging

- there is 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 to some degree

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 the 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 as a result of cell-killing therapies

Neurodegeneration and Damage to the Brain

- lots of interesting correlations in aging and neurodegeneration, e.g. aortic stiffness correlates with cognitive decline

- remains unclear as to whether causation is involved, or there is an underlying causes 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 Alzheimer's disease

- evidence points to microglial dysfunction in the development of neurodegenerative conditions

- assays for the early stages of neurodegenerative conditions will likely soon improve greatly

- in mice there is a narrow therapeutic window for exercise to improve neurogenesis

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

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