So you’ve looked after your health, augmented your body as much as transhumanly possible and living forever. But who wants to live forever in the body of a centenarian? Rejuvenation technologies will be the natural bonus of life extension technologies, i.e. they will slow aging down so much eventually they will start to reverse it.
This section has information regarding how bodies will be repaired (e.g. replacement organs) and physiological age reduced.
Reversing aging by removing wrinkles inside our cells – Science Daily – 29-May-2018
Fatty liver disease may result from our cells’ nuclei getting wrinkly.
Disfiguration of our DNA compartment could cause other unwanted effects of aging.
Genes that are turned off are shoved up against the nuclear membrane.
Aged nuclear membranes become irregular and prevent turning off.
Wrinkling stems from a lack of cellular protein lamin.
Could use viruses to deliver lamin back to cells.
XPO1 inhibition increases autophagy and lifespan – News Medical – 16-May-2018
Reducing the expression of XPO1 led to an increased concentration of TFEB.
This was associated with an increase in autophagy markers.
Lifespan of nematodes was increased by 15 to 45%.
Similar effect with selective inhibitors of nuclear export (SINE).
Treating human cells with XPO1 inhibition saw an increase in markers of authophagic activity.
Can autophagy boost your health? – BBC News – 6-May-2018
Autophagy is the process by which cells degrade and recycle their components.
Helps infection control and protects against excessive inflammation.
Stimulating the process in mice result in them living longer.
Could remove clumped proteins to protect against neurodegenerative diseases.
Rejuvenating the Mitochondria (VIDEO) – Google Tech Talks – 15-Dec-2016
Engineering Approaches to Combating the Diseases and Disabilities of Aging.
Matthew O’Connor talks about the work of the SENS Research Foundation to fight age related diseases with a focus on repairing the damage that accumulates as we age.
Anti-aging breakthrough could extend healthspan by making old cells young again – New Atlas – 8-Nov-2017
Instead of clearing out senescent cells scientists have found a way to rejuvenate them.
New treatment uses compounds called resveratrol analogs, resveralogues.
Within hours of being treated senescent cells started to display more splicing factors.
Cells also expressed longer telomeres, re-entered cell cycle and resumed proliferation.
Scientists decipher mechanisms underlying the biology of aging – Phys – 2-Nov-2017
Used a combination of engineering, computer science and biology to analyze molecular processes.
Chromatin silencing helps protect DNA from damage.
Also stops RNA expression so excessive silencing could derail normal cell physiology.
Cells switch their DNA between states periodically during aging.
When cells grow old, they lose their ability to maintain this periodic switching.
Protein Signalling Implicated in Age-Related Hair Graying – Fight Aging – 25-Oct-2017
Hair follicle undergoes repetitive cyclic regeneration.
Aging phenotypes include irreversible hair loss, hair thinning and graying.
Wnt signaling promotes differentiation of melanocyte stem cell, exhaustion of which leads to hair graying during aging.
Wnt3a induces melanocyte stem cell differentiation in vivo and in vitro.
Demonstrated accelerated hair graying by increasing Wnt signaling.
Not known if reverse effect can be produced via suppression of this pathway in older animals.
Rejuvenating the Thymus to Prevent Age-related Diseases – LEAF science – 4-Oct-2017
Thymus gland produces the majority of body’s T cells.
Thymus shrink with age making us increasingly vulnerable to infectious diseases.
T-cell-based immunity begins to collapse in the 60s.
Superficial tests of immune system aging showed improvements in 8 out of 9 men.
Full details being prepared for publication.
Interview with Dr. Greg Fahy – Chief Scientific Officer at 21st Century Medicine
BioTime’s CEO: Human Aging Will Soon Become a Thing of the Past – Mauldin Economics – 06-June-2017
Cells become dysfunctional or die with aging.
Now able to manufacturer any of the cellular building blocks of the human body.
On an industrial scale of millions of people.
Manufactured cells are young cells.
Clear that we’re going to be able to reverse age related changes in the body.
Repairing Mitochondrial DNA for Age-related Diseases – LEAF – 2-May-17
University of Sheffield has made progress in repairing the damage done to mitochondrial DNA (mtDNA).
One of the hallmarks of aging is genomic instability which includes damage to the mtDNA.
mtDNA is more vulnerable to damage, due to its proximity to energy generating processes.
Dysfunctional mitochondrial mutants are able to avoid mitophagy.
Entire cell can become populated with mutant mitochondria – not generating ATP properly.
5 year study reveals how the enzyme TDP1 is also responsible for repairing damaged mtDNA.
Treating Diseases with a Protein Missile System – LEAF – 26-May-17
University of Dundee demonstrate AdPROM to target and destroy specific proteins within cells.
Affinity-directed PROtein Missile uses small affinity probes which bind and recruit target proteins to the cellular protein degradation system to be destroyed.
In the majority of diseases protein function is altered due to genetic mutation or a deregulated environment.
During aging, proteins can become misfolded which leads to protein aggregation and the onset of diseases like Alzheimer’s.
COMMENT: could also be used to target some of the SENS strategies such as LysoSENS
Repairing Mitochondrial DNA for Cancer and Age-related Diseases – LEAF – 2-May-2017
Mitochondrial dysfunction plays a key role in aging.
Mitochondria have their own DNA separate from our own.
Errors in its DNA accumulate as a result of free radical damage and contribute to aging.
5 year study found that TDP1 is responsible for repairing damaged mtDNA.
Also, a Protein known as TOP1 is responsible for untangling the mtDNA when it gets tangled.
Could lead to the development of new therapies to treat mitochondrial disease.
Induced Pluripotency to Enable Rejuvenation of Blood Production – Fight Aging! – 23-Feb-2017
Induced pluripotency appears to produce a form of cellular rejuvenation.
How do old gamete cells produce young offspring who lack the molecular damage of aging?
Is there any way to adapt this process of rejuvenation for use in therapies?
Exciting Therapy To Treat Age Related Blindness Moving To The Clinic – LEAF – 15-Feb-2017
Ichor Therapeutics is a biotechnology company focused on developing drugs for age-related diseases.
LYSOCLEAR for age-related macular degeneration and Stargardt’s macular degeneration going into Phase I clinical trials.
Age-related macular degeneration (AMD) is the leading cause of vision loss among people over the age of 50.
With time, different by-products are formed that accumulate in the lysosomes of RPE cells.
LYSOCLEAR is an enzyme product that can enter the lysosomes of RPE cells and destroy toxic A2E accumulations.
We are now seeing the first SENS therapies proposed back in 2000s moving into clinical trials.
Fight Aging predicts the sequence of arrival for meaningful antiaging therapies – Next Big Future – 30-Nov-2016
Each treatment will target a different type of molecular damage in cells and tissues.
1) Clearance of Senescent Cells
2) Immune System Destruction and Restoration
3) Clearance of the First Few Types of Amyloid
4) Clearance of Glucosepane Cross-Links
5) Thymic Rejuvenation to Increase the Supply of Immune Cells
6) Mitochondrial Repair
7) A Robust Cure for Cancer
8) Reversing Stem Cell Aging
9) Clearance of Other Amyloids, Aggregates, and Sundry Lysosomal Garbage
Scientists to ‘reset’ blood proteins in attempt to slow ageing process – Guardian – 22-Nov-2016
Participants will have their blood passed through a machine that resets abnormal levels of proteins seen in older blood.
Clinical trial planned in the next six months.
DNA repair and metabolism as determinants of species longevity – eLife Sciences – 22-Nov-2016
Mammalian lifespan differs by >100-fold
Skin fibroblasts from 16 species of mammals studied under identical cell culture conditions.
Key features of cells from longer-lived species:
1. up-regulated genes involved in DNA repair and glucose metabolism
2. down-regulated proteolysis and protein transport
3. high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine
Removing mutated DNA from mitochondria to turn back the aging clock – Caltech – 18-Nov-2016
Hundreds to thousands of mitochondria per cell each carrying its own mtDNA.
mtDNA has limited repair abilities resulting in heteroplasm.
When a critical threshold level of mutant mtDNA is passed, cells become nonfunctional or die.
Cells can break down and remove dysfunctional mitochondria through a process called mitophagy
When Caltech researchers artificially increased the activity of genes that promote mitophagy in fruit flies the fraction of mutated mtDNA in muscle cells was dramatically reduced.
For example, parkin which is mutated in familial forms of Parkinson’s disease reduced the fraction of mutant mtDNA from 76 percent to 5.
Mechanotherapy regenerates injured muscle tissue – Kurzweil AI – 28-Jan-2016
Could replace or enhance drug- and cell-based regenerative treatments.
2 techniques tested – ferrogel implant and pressurized cuff
Two-and-a-half-fold improvement in muscle regeneration and reduced tissue scarring in 2 weeks.
Physical and mechanical factors play very critical roles in regulating biology.
Direct stimulation of muscle tissue increases the transport of oxygen, nutrients, fluids and waste removal from the site of the injury.
Self assembling biological tissue-like material grown in lab – Queen Mary University of London – 28-Sep-2015
QMUL create materials using peptides and proteins that self-assemble to form a dynamic tissue.
No moulds or 3D printing.
Exhibits biological tissue behaviors such as growth, morphogenesis and healing.
Can be guided to grow into complex shapes – could lead to artificial arteries.
VIDEO: time lapse video of tissues being grown
3D-printed guide helps regenerate complex nerves – Kurzweil AI – 18-Sep-2015
Regrowth of nerves after injury or disease is very rare.
New technique 3D imaged and 3D printed a custom silicone guide with biomimetic physical cues (microgrooves) and path-specific biochemical cues.
Successfully tested on rat’s sciatic nerve.
Don’t have to worry whether the drugs will work and be safe in humans, but won’t have original 3D scan after an accident so use library of standard nerves instead.
Investigating the Mechanisms of Remyelination – Fight Aging! – 7-Sep-2015
As well as diseases such as multiple sclerosis everyone suffers demyelination as part of aging.
Affects cognitive function even in the fit older people.
Study finds pleiotrophin inhibitor could be an effective treatment.
Rejuvenation Biotechnology 2015 : Thoughts on Thymus Regeneration – Fight Aging! – 24-Aug-2015
Regeneration of the thymus is one of a number of possible ways to introduce much larger numbers of fresh new immune cells into an old body,
Discusses 2 key strategies for longevity:
1. engineer metabolism to make the damage of aging accrue more slowly
2. leave metabolism as-is and periodically repair the damage
Axons grown across chronic spinal cord injury (SCI) – Kurzweil AI – 17-Jul-2015
Deleting PTEN gene in mice neurons stimulated growth of axons across damaged nerve up to 1 year after the original injury.
Building and transplanting a bioengineered forelimb – 05-Jun-2015 – Kurzweil AI
Functioning rat forelimb grown using decellularization / recellularization (decel/recel) technique
First human head transplant planned – The Independent – 8-Apr-15
Energy for muscles and brains controlled by a single protein – Salk Institute – 7-Apr-15
A simple, non-invasive gene therapy restores sight – Kurzweil AI – 14-Jun-13
How to quickly generate a large quantity of personalized nerve cells – Kurzweil AI – 14-Jun-13
Lifespan-extending drug given late in life reverses age-related heart disease in mice – Kurzweil AI – 12-Jun-13
Organ, tissue replacement could end aging by mid-2020s – Dick Pelletier, IEET – 14-May-13
Gene therapy: ‘Heart-healing virus’ trial starts – BBC News – 30-Apr-13