"Beauty does not linger, it only visits.
Yet beauty's visitation affects us and invites us into its rhythm.
It calls us to feel, think,
and act beautifully in the world:
to create and live a life
that awakens the Beautiful."
- John O'Donohue,
Beauty: The Invisible Embrace, 2005
"You only live once, but if you do it right, once is enough." - Mae West
4 Habits of ‘SuperAgers’
by Lee A. Lindquist, MD, MPH, Updated 2023
Excerpts:
1. SuperAgers live an active lifestyle.
2. SuperAgers continue to challenge themselves.
3. SuperAgers are social butterflies.
4. SuperAgers indulge.
How to Become a Superager
By Professor Lisa Feldman Barrett, psychologist and neuroscientist, Northeastern University, 31 Dec. 2016, New York Times
[Prof. Barrett's 2017 TED tallk "You aren't at the mercy of your emotions - your brain creates them" has been viewed over 7 million times.]
Excerpts
... Why do some older people remain mentally nimble while others decline? “Superagers” (a term coined by the neurologist Marsel Mesulam) are those whose memory and attention isn’t merely above average for their age, but is actually on par with healthy, active 25-year-olds. My colleagues and I at Massachusetts General Hospital recently studied superagers to understand what made them tick.
... What are these crucial brain regions? If you asked most scientists to guess, they might nominate regions that are thought of as “cognitive” or dedicated to thinking, such as the lateral prefrontal cortex. However, that’s not what we found. Nearly all the action was in “emotional” regions, such as the midcingulate cortex and the anterior insula. . . . ... if people consistently sidestep the discomfort of mental effort or physical exertion, this restraint can be detrimental to the brain. All brain tissue gets thinner from disuse. If you don’t use it, you lose it.
... take up a challenging activity. Learn a foreign language. Take an online college course. Master a musical instrument. Work that brain. Make it a year to remember. >>>more
Flow state, exercise and healthy ageing: 5 unexpected benefits of singing By Assoc. Prof Melissa Forbes, Contemporary Singing-Music,
University of Southern Queensland, 14 April, 2022
Excerpt:
Singing with others feels amazing. Group singing promotes social bonding and has been shown to raise oxytocin (the “bonding hormone”) and decrease cortisol (the “stress hormone”).
But it’s not just about singing in groups. There are many unexpected ways singing is good for you, even if you’re on your own.
Singing is a free and accessible activity which can help us live happier, healthier and more fulfilling lives.
And before you protest you are “tone deaf” and “can’t sing”, research shows most people can sing accurately in tune, so let’s warm up those voices and get singing. >>> more
Immortality... reality? The Fountain of Youth: Human Lifespan – longevity – immortality
Imagine a life spanning more than a century, in good health – and packed with several careers.There's a concerted effort underway within science and medicine to push the boundaries of the human lifespan - to as long as a thousand years!
"Human cells can divide a limited number of times before their DNA becomes corrupt, but could advances in genetic technology allow cells to divide infinitely?"
"Aging is by far the biggest killer of people. The diseases that you will all die of are actually the symptoms of aging: cardiovascular disease, cancer, Parkinson's Disease, Type 2 Diabetes, all of these diseases are actually the symptoms of an underlying disease. That is the disease of aging. ...There is no reason humans have to age. We've seen already in other species organisms that don't age. ... There is no reason, in principle, why in addition to using regenerative medicine and stem cell therapy we couldn't understand the basic biology of ageing and attack the disease at its root cause. ... Survey after survey of people across the ages, show that if anything, life satisfaction and happiness slightly increase as people get older. The things that cause people to be unhappy or dissatisfied with their lives are diseases, illnesses and disabilities. Not the mere fact that they are 80, 90, or 100. If you look at the surveys on happiness and life-satisfaction, they are a U-shaped curve with the low point at about in the 40s. And then they increase as you get older. There is no evidence that people find life boring or uninteresting though they find disease and disability painful and want to be rid of it."
– Professor Julian Savulescu, Director of neuro-ethics and the Institute for Science and Ethics, University of Oxford.
Professor Fiona Wood "...The greatest impacts on human longevity follow vast changes in quality of life: clean water and clean food and infection control.
Understanding our genetics will give us opportunities to taylor health care in such a way that maybe we can change the outcomes considerably.... Is there some way that we can look at self-organization and tissue regeneration such that we could change the way we age. ...repair ourselves against normal wear and tear?"
Dr Brad Partridge: "Stem cell technologies, oncological interventions - 'calorie restriction memedics' might be able to extend our life-span to 140-150 and produce 90 year olds that look like 50 year olds. There are ethical questions: some say this is going against nature while others say we really need a war on aging. ...and big pharmaceutical companies are taking this research very seriously."
Collective failure to manage the human factor contributes to the threat of infection, and the very real consequences for those afflicted by diseases such as influenza, malaria and childhood infections. Devising, implementing and enforcing a strategy to remedy this will require a behaviour change derived from a new understanding of collective moral responsibility.>>>more
2. Susan Pinker Psychologist Susan Pinker reveals how in-person social interactions are not only necessary for human happiness but also could be a key to health and longevity
Susan Pinker is a columnist for The Wall Street Journal where she writes a
column on human behavior, Mind and Matter. Her writings have been credited with 'shaking up preconceived ideas' on gender issues: arguing "that biological differences could play an unexpectedly large role in creating classroom, lifespan and workplace gender gaps (The Sexual Paradox, 2008). With The Village Effect, (2014), she tracks another current: how social, face-to-face interactions are critical not only for our happiness but also for our survival, and how technology can isolate us from these life-saving bonds. As she writes:
"Neglecting to keep in close contact with people who are important to you is at least as dangerous to your health as a pack-a-day cigarette habit, hypertension or obesity."
With a background in fundamental theoretical physics and cosmology, Paul Davies (b. 1946-) began examining the evolutionary roots of cancer:
"Evidence is mounting that the micro-environment at the cells’ destination plays a key role in the success of metastasis. … deep links between embryogenesis and tumorigenesis have been found..."
In other words, when oxygen is low, aka pH acidosis, "opportunistic primordial cells" will 'de-couple' from the body's immune system to form a 'tumour' that looks very much like the early stages of embryonic development, aka 'cancer tumours':
"Cancer has long been recognised as a throwback to a "selfish cell" era. But recent advances in research permit us to embellish this picture. For example, cancer cells thrive in low-oxygen (even zero-oxygen) conditions, reverting to an earlier, albeit less efficient, form of metabolism known as fermentation."
–– Paul Davies See more detailed reports under Part 2, Physics:
4. Michael Rose: evolutionary biology
“biological fitness is at the core of health” Back to top
Director and Professor at the Department of Ecology and Evolutionary Biology at the University of California, Irvine, Professor Michael Rose (b. 1955 -) has worked in the field of aging, biological immortality, and human evolution since the 1980s, to prove that "resistance to various stresses was a key factor in postponed aging."
Professor Michael Rose: "Out of respect for both science and medicine, the following propositions are open for discussion throughout the World-Wide Web." "The 55 thesis on the Power and Efficacy Of Natural Selection for Sustaining Health" -
Excerpts: 4. Natural selection results in the evolution of good health only when there is sufficient heritable variation affecting survival and reproduction.
...
52. All people without significant agricultural ancestry should revert to patterns of nutrition and activity which have physiological effects like those of hunter-gatherer lifestyles, in order to slow their aging and hasten its cessation.
Professor Rose
has authored over 275 Academic publications and 10 books, including Does Aging Stop? (2011), Evolutionary Biology of Aging (1991).
"Just as Einstein and the modern physicists banished simple-minded physics, 21st Century biology is demolishing the crudely mechanistic thought of molecular biology. In its place we now see glittering webs of life. And these webs are not just mystical objects fit only for worship. Rather they are the very stuff from which the new sciences of life are being spun...."
... that aging is caused by genes that have two effects, one acting early in life and the other much later. The genes are favored by natural selection as a result of their early-life benefits, and the costs that accrue much later appear as incidental side-effects that we identify as aging. Dr. Rose has also suggested that aging can stop in a latter stage of life.
Rose’s laboratory has conducted the longest-running artificial selection experiment designed to test the theory of antagonistic pleiotropy. Fruit flies (Drosophila melanogaster) are being bred for longevity by collecting eggs from the longest-lived flies in each generation. The experiment has run since 1981, and has produced flies with quadruple the original life span. The prediction of the antagonistic pleiotropy hypothesis was that these long-lived flies would have much lower fertility early in life. The result has been the opposite – that the long-lived flies actually lay more eggs at every stage of life. The long-lived flies show other weaknesses that would make them poor competitors in the wild, and perhaps these traits are the true areas of antagonistic pleiotropy. In 1997, Rose was awarded the Busse Research Prize by the World Congress of Gerontology. He has authored The Long Tomorrow: How Advances in Evolutionary Biology Can Help Us Postpone Aging which is one of 10 authored books.
Dr. Rose suggests that aging is a result of “declining forces of natural selection.” He points to studies of the demographic data in large-scale fruit fly experiments and actuarial data for humans which he believes support the hypothesis that acceleration in death rates can halt in later life. According to Rose, mortality-rate plateaus have not often been noticed in humans because they are only seen in specific-age cohorts of the very old. His proposed explanation is that at a stage of life beyond the potential to reproduce, the effect of natural selection is no longer falling as it has ‘bottomed out’. Rose suggests that if a decline in the effect of natural selection is responsible for aging, then when this decline finally ends, at post-reproductive age, aging could halt. He reasons it follows that aging is “not a cumulative process of progressive chemical damage, like rust, at late ages, aging can stop”.
According to Rose, relative to the age of reproductive maturity a transition to the late-life stage of life occurs much later in humans than in the populations of flies for which there are data. In humans, the ‘late-life’ stage of life is only reached at 90 years old, whereas the data for flies scaled to humans would predict a ‘late-life’ stage for humans at 40–50 years old. Rose suggests that human populations’ adoption of agriculture led to more children surviving to adulthood, and to reproduction occurring later in life. Agriculture is also hypothesized by Rose to have resulted in high population density, thereby increasing the range of ages not under selection.
5. Bruce Lipton: anatomy
“The Biology of Belief” Back to top
From 1987 to 1992, Professor of Anatomy Bruce Lipton (b. 1944-) was involved in the early stages of stem cell research at Penn State and Stanford University Medical Center. The author of several books, including his international best-seller, “The Biology of Belief” (2005), which, on the 10th anniversary, in 2015, he gave away! Free download: "The Biology of Belief" in pdf format
Professor Lipton's insights appealed beyond academic circles because he shared the personal life drama that led to of his groundbreaking scientific insight - that genes can be turned on and off by environmental signals from outside the cell, including thoughts, feelings and emotions.
"What would your life be like if you learned that you are more powerful than you have ever been taught?" ... "We can control our lives by controling our perceptions.” ... “The overuse of prescription drugs provides a vacation from personal responsibility.”
– Dr. Bruce H. Lipton, Professor of Anatomy, Stanford University
Dr. Bruce Lipton explains how our body replaces 1 billion cells every hour: "Everything we think, feel, do, and eat in an hour influences that cell replacement more than stem cell therapy... Genes can be turned on and off by environmental signals from outside the cell, including thoughts, feelings and emotions."
"We perceive ourselves as single individual entities. The truth is we are actually comprised of upwards to 50 trillion individual living cells."
Dr Lipton explained how very one of our cells has a brain, a digestive system, and a reproductive system, and that millions of our body's cells are shed and replaced every hour: Ergo, everything we think, feel, say, do in that time impacts the growth of new cells.
In this April 2012 YouTube interview, Professor Lipton said,
"Each cell is a sentient being, so therefore each cell is like a citizen in a large community of 50 trillion entities in one population. So the body is not a single entity. It is a community. In the body, the shared vision that coordinates all the functions of the cell is what we call 'the mind'. The mind is like a government for the 50 trillion cells. But the moment you introduce fear into the system, that is the first thing that causes the community to break down. Fear is the primary cause of the stresses that promote the illnesses and diseases that we face as humans.
"If we could ultimately get rid of fear in our population, then basically we would put all of our reserves, all of our energy and all of our body systems into the mode of growth and maintenance, and therefore, not only would we be healthy as individuals, but then, as a community, all healthy individuals in a community would raise the level of life in that particular community so that there is the great possibility of a future of growth and peace and harmony once the concept of fear is removed from our belief system."
– Bruce Lipton, 2012, YouTube interview
6. Mark P. Mattson: neuroscience
"elucidating cellular signaling mechanisms" - "calorie restriction memedics" Back to top Professor of Neuroscience at Johns Hopkins University, Mark P. Mattson (b. 1957-) is the former Chief of the Laboratory of Neurosciences at the National Institute on Aging Intramural Research Program of the National Institute on Aging.
Cellular and Molecular Mechanisms of Brain Aging and Neurodegenerative Disorders Excerpt: A multifaceted array of experimental models of aging and age-related neurodegenerative disorders are being employed in order to establish the molecular and biochemical changes that occur during aging and in disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and stroke. Data obtained in these experimental models are integrated with data obtained in studies of both normal elderly humans and patients with neurodegenerative disorders to arrive at conclusions as to why neuronal dysfunction and degeneration occur in the disorders. In addition to identifying the molecular and cellular alterations that lead to neuronal degeneration in age-related neurological disorders, investigators are elucidating the cellular signaling mechanisms that allow successful brain aging.
Perhaps of equal importance to knowledge of the molecular and cellular mechanisms that result in neuronal dysfunction and death in age-related neurodegenerative disorders, is a better understanding of successful brain aging at the cellular and molecular levels. It is clear that such "anti-aging" signaling mechanisms exist because some individuals can live for more than a century with very little decline in their cognitive or motor capabilities. . . The cellular and molecular mechanisms that mediate the beneficial effects of dietary restriction (DR) on brain plasticity and resistance to injury are being studied. >>>more
... a TEDx talk given by Mark Mattson, the current Chief of the Laboratory of Neuroscience at the National Institute on Aging. He is also a professor of Neuroscience at The Johns Hopkins University, and one of the foremost researchers in the area of cellular and molecular mechanisms underlying multiple neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. I chose to include ‘Big Pharma’ in the title because that’s exactly what it is. There have been countless examples of the manipulation of published research at the hands of pharmaceutical companies in recent years. This is why Harvard Professor of Medicine Arnold Symour Relman told the world that the medical profession has been bought by the pharmaceutical industry. It’s why Dr. Richard Horton, Editor in Chief of The Lancet, recently stated that much of the sceintific literature published today is simply untrue.>>> more
Aubrey de Grey:biogerontology
"an engineering problem."
Humans age in 7 basic ways, all of which can be averted.
Cambridge biomedical gerontologist Aubrey de Grey (b. 1963-) argues that aging is a curable disease and challenges the most basic assumption underlying the human condition —that aging is inevitable. DeGrey argues that aging can be cured if it's approached as "an engineering problem." Hence, Strategies for Engineered Negligible Senescence (SENS)
(from Latin: senescere, meaning "to grow old”)
In 2011, Dr. Aubrey de Grey inherited roughly $16.5 million on the death of his mother. Of this he assigned $13 million to fund the SENS Research Foundation for the development of a wide range of therapies applied in repairing and reducing age-related infirmity and damage to human tissue:
Dr. De Grey's plan calls for identifying all the components that cause human tissue to age, and designing remedies for each of them
– forestalling disease and eventually pushing back death.
- Mutations – in Chromosomes causing cancer due to nuclear mutations/epimutations:
These are changes to the nuclear DNA(nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA. Certain mutations can lead to cancer, and, according to de Grey, non-cancerous mutations and epimutations do not contribute to aging within a normal lifespan, so cancer is the only endpoint of these types of damage that must be addressed.
Mitochondria are components in our cells that are important for energy production. They contain their own genetic material, and mutations to their DNA can affect a cell's ability to function properly. Indirectly, these mutations may accelerate many aspects of aging.
- Junk – inside of cells, aka intracellular aggregates:
Our cells are constantly breaking down proteins and other molecules that are no longer useful or which can be harmful.
Those molecules which can't be digested simply accumulate as junk inside our cells.
Atherosclerosis, macular degeneration and all kinds of neurodegenerative diseases (such as Alzheimer's disease) are associated with this problem.
- Junk – outside of cells,
aka extracellular aggregates:
Harmful junk protein can also accumulate outside of our cells. The amyloid senile plaque seen in the brains of Alzheimer's patients is one example.
- Cells – too few, aka cellular loss:
Some of the cells in our bodies cannot be replaced, or can only be replaced very slowly – more slowly than they die. This decrease in cell number causes the heart to become weaker with age, and it also causes Parkinson's disease and impairs the immune system
This is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other things that they're not supposed to, like secreting proteins that could be harmful.
Cell senescence has been proposed as cause or consequence of type 2 diabetes.
Immune senescence is also caused by this.
- Extracellular protein crosslinks:
Cells are held together by special linking proteins. When too many cross-links form between cells in a tissue, the tissue can lose its elasticity and cause problems including arteriosclerosis and presbyopia
Dr. de Grey’s book "Ending Aging" (2008) outlines seven strategies for ending aging, which are based on seven causes of aging he has identified:
1. Extracellular junk
2. Cell senescence
3. Extracellular crosslinking
4. Intracellular junk
5. Mitochondrial mutations
6. Cancer-causing nuclear mutations
(and epimutations)
7. Cell loss leading to tissue atrophy.
Each strategy program of Strategies for Engineered Negligible Senescence is given a distinctive “SENS” name, as follows:
1. AmyloSENS (extracellular junk) – Aging leads to an accumulation of junk outside of cells, the most notorious example of which is the amyloid plaque that is believed to cause Alzheimer’s disease. AmyloSENS would attempt to use the immune system to eliminate amyloid and other damaging extracellular junk.
2. ApoptoSENS (cell senescence) – Cells that become old and no longer divide (senescent cells) produce inflammatory substances that contribute to many of the diseases of aging. ApoptoSENS would eliminate senescent cells by inducing such cells to “commit suicide” (apoptosis).
3. GlycoSENS (extracellular crosslinks) – Proteins form cross-links with sugars (glycation) as tissues age. As a result of this crosslinking, tissues lose suppleness, becoming stiff and full of fibrous material. GlycoSENS seeks enzymes that will selectively breakdown these harmful crosslinks.
4. LysoSENS (intracellular junk) – Waste material of various kinds (“junk”) that is formed within cells is often broken down by a specialized organelle called the lysosome, which contains enzymes for that purpose. Unfortunately, some junk (proteins, fats, metals, etc.) cannot be broken down by normal lysosome enzymes, and this junk accumulates with age. The goal of LysoSENS is to develop and provide additional enzymes to the lysosomes that would break down more forms of junk molecules.
5. MitoSENS (mitochondrial mutations) – Mitochondria generate energy for cells, but in doing so they generate large amounts of free radicals. A prime target for these free radicals is the DNA within the mitochondria that controls mitochondrial function. MitoSENS seeks to make copies of mitochondrial DNA in the DNA of the cell nucleus, where it would be a safe distance from the damaging free radicals produced within the mitochondria.
6. OncoSENS (cancer-causing nuclear mutations/epimutations) – Most forms of cancer utilize the enzyme telomerase to maintain long telomeres (the caps of chromosomes that keep them functional). OncoSENS proposes to eliminate telomerase as a means of controlling cancer. Telomeres are needed by stem cells, but OncoSENS would replace this need by a program of tissue replacement (RepleniSENS).
7. RepleniSENS (cell loss and atrophy) – With age, cells are lost or atrophy, thereby causing tissues to stop functioning properly. RepleniSENS would utilize stem cell therapies to restore cells and tissues.
Alex Zhavoronkov: biomedicine
“Our mission is to accelerate drug discovery..."
Alex Zhavoronkov Ph.D. (b. 1980-), the founder of Insilico Medicine, has stated:
“Our mission is to accelerate drug discovery and drug development by continuously inventing and deploying new artificial intelligence technologies.” Linkedin: "Insilico Medicine (www.insilico.com) now directly or indirectly employs over 100 scientists with R&D centers in the US, Greater China, Russia, and R&D resources in the UK, and Belgium with half of them focused exclusively on developing and applying deep learning methods to drug discovery.
August 4, 2021
Longevity Technology Insilico announce new milestone in kidney fibrosis Generative biology AI-powered drug discovery results in nomination of a novel small molecule preclinical candidate for kidney fibrosis.
Excerpt:
A systems approach to antifibrotic drug discovery, enabled by a sophisticated deep learning (DL)-driven target identification platform PandaOmics, in concert with lead discovery platform Chemistry42, allowed Insilico Medicine to rapidly achieve drug design success with two fibrotic indications – development of novel preclinical drug candidate for IPF within under 18 months, and, more recently, a novel milestone in kidney fibrosis.
Complexity of kidney fibrosis is paramount, and understanding disease mechanisms requires cutting-edge technologies and systems approaches. The application of AI, more specifically Deep Learning, has proved to be beneficial at every step of the drug discovery process, especially at the hypothesis generation and target identification stage. The ability to process multimodal big data and build sophisticated disease models for target selection was the key advantage for Insilico Medicine, when the company decided to enter the fibrosis drug discovery space with its AI-platforms PandaOmics and Chemistry42. The platforms include hundreds of modules such as generative adversarial neural nets (GANs), natural language processing (NLP) engines, and statistical components, all working in concert.
In 2020, the Insilico team achieved the first major proof-of-concept success in the area of fibrosis using its integrated drug discovery platform, based on generative adversarial networks (GANs). As a result, they discovered a novel intracellular pan-fibrotic target, and designed a drug candidate that showed outstanding in vivo results for Idiopathic Pulmonary Fibrosis. >>>more
If we zoom out of the mundane and take a bird’s eye view on life, it is simple. We are born, we grow, we reproduce, we take care of our young while gradually declining, and then we die of a long and terrible or short and not so terrible disease. The millions of years of evolution polished us to accept this paradigm, and the inability to change had made us very content with the situation.
…
While there is a lot of talk about the growing income inequality and the increasing gap between the rich and the poor, the difference in overall utility one can get in this life is rapidly decreasing. There are few real necessities people cannot go without, namely food, clean water, shelter, sleep, and basic entertainment. Think of the mobile phone. The rich can get a slightly better package but the net utility between the cheap Android and the most expensive iPhone will be marginal. Regardless of how rich you are, you cannot buy a better phone, or a smartwatch, or a video game, or a better movie, compared to a middle-class citizen. One does not fly business class to arrive earlie
The arbitrary separation of the classes, ethnic groups, races, and nations is only drawing our attention away from the most important and unsolved challenge - aging. Regardless of how much money you have, you cannot live substantially longer or better. Aging does not discriminate and death comes to us all. Life does not provide a path for continuous improvement. Aging is a universal equalizer.
If I managed to capture your attention with the above preamble, in this short article I would like to achieve three objectives:
Introduce the notion of effective altruism
Explain the concept of QALY -- quality-adjusted life year -- maximization
Propose an idea that focusing on longevity biotechnology is the most effective way to maximize QALY >>>continue
It's hard to argue that scientists shouldn't find ways to help people live longer. Zhavoronkov argues that longevity ought to be a fundamental human right — the right to live as long and well as possible. Democratizing longevity technology across society would mean reducing or ending many of the diseases and conditions facing people today.
July 2023
Science Direct Conceptual Breakthroughs in the Evolutionary Biology of Aging
Arnold, Rose, Avise.
Key Features
- Reviews cell-molecular theories of aging in the light of evolutionary biology
- Offers an evolutionary analysis of prospects for mitigating aging not commonly discussed within private and public sectors
- Provides readers with a radically different perspective on contemporary biological gerontology, specifically through the lens of evolutionary biology
April 2022
Science Genome-wide analysis of somatic noncoding mutation patterns in cancer, Felix Dietlein et al.
INTRODUCTION
A central hallmark of tumor development is that cancer cells acquire somatic mutations in their genomes that are not present in normal tissue. Some mutations are drivers and contribute to the growth of tumor cells, but many others are passengers without apparent effects on tumor biology. Over the past decade, driver mutations have been comprehensively characterized in protein-coding genomic regions by analyzing sequencing data from thousands of tumor-normal pairs. This characterization in protein-coding regions has yielded a wealth of insights into tumor biology, including many genome-inspired drug targets. However, the role of somatic mutations in the other 98% of the cancer genome—the noncoding genome—remains incompletely understood.
…
Abstract
We established a genome-wide compendium of somatic mutation events in 3949 whole cancer genomes representing 19 tumor types. Protein-coding events captured well-established drivers. Noncoding events near tissue-specific genes, such as ALB in the liver or KLK3 in the prostate, characterized localized passenger mutation patterns and may reflect tumor-cell-of-origin imprinting. Noncoding events in regulatory promoter and enhancer regions frequently involved cancer-relevant genes such as BCL6, FGFR2, RAD51B, SMC6, TERT, and XBP1 and represent possible drivers. Unlike most noncoding regulatory events, XBP1 mutations primarily accumulated outside the gene’s promoter, and we validated their effect on gene expression using CRISPR-interference screening and luciferase reporter assays. Broadly, our study provides a blueprint for capturing mutation events across the entire genome to guide advances in biological discovery, therapies, and diagnostics.
More VEGF, more life span and health span
Advanced aging is celebrated but its ill effects of deterioration at the cell, tissue, and organ levels are not. Grunewald et al. provide evidence for the vascular theory of aging, which reports that an age-related decrease of vascular function is a driver of organismal aging at large (see the Perspective by Augustin and Kipnis). Vascular endothelial growth factor (VEGF) signaling insufficiency underlies this vascular insufficiency in aged mice. A modest compensatory increase in circulatory VEGF was sufficient to preserve a young-like vascular homeostasis, alleviate multiple adverse age-related processes, and ameliorate a host of age-associated pathologies in mice.
. . . CONCLUSION
The study provides compelling evidence for the proposition that vascular aging is a hierarchically high driver of overall organismal aging. It places VEGF signaling insufficiency at center stage to multiorgan aging and suggests that its undoing might confer comprehensive geroprotection.
“Telomere shortening and malfunction have been linked to cell aging and age-related diseases, including cancer.”
Molecules that accumulate at the tip of chromosomes are known to play a key role in preventing damage to our DNA. Now, researchers at EPFL have unraveled how these molecules home in on specific sections of chromosomes—a finding that could help to better understand the processes that regulate cell survival in aging and cancer.
Much like the aglet of a shoelace prevents the end of the lace from fraying, stretches of DNA called telomeres form protective caps at the ends of chromosomes. But as cells divide, telomeres become shorter, making the protective cap less effective. Once telomeres get too short, the cell stops dividing. Telomere shortening and malfunction have been linked to cell aging and age-related diseases, including cancer.
Scientists have known that RNA species called TERRA help to regulate the length and function of telomeres. Discovered in 2007 … TERRA belongs to a class of molecules called noncoding RNAs, which are not translated into proteins but function as structural components of chromosomes. TERRA accumulates at chromosome ends, signaling that telomeres should be elongated or repaired.
However, it was unclear how TERRA got to the tip of chromosomes and remained there. "The telomere makes up only a tiny bit of the total chromosomal DNA, so the question is 'how does this RNA find its home?’”…
Finding home
By visualizing TERRA molecules under a microscope, the researchers found that a short stretch of the RNA is crucial to bring it to telomeres. Further experiments showed that once TERRA reaches the tip of chromosomes, several proteins regulate its association with telomeres. Among these proteins, one called RAD51 plays a particularly important role, …
RAD51 is a well-known enzyme that is involved in the repair of broken DNA molecules. The protein also seems to help TERRA stick to telomeric DNA to form a so-called "RNA-DNA hybrid molecule". Scientists thought this type of reaction, which leads to the formation of a three-stranded nucleic acid structure, mainly happened during DNA repair. The new study shows that it can also happen at chromosome ends when TERRA binds to telomeres. "This is paradigm-shifting," ... >>>more
February 2017 "The good life is built with good relationships"
By Melanie Curtin,
INC Australia
Some wisdom gleaned from one of the longest longitudinal studies ever conducted: According to George Vaillant, the Harvard psychiatrist who directed the study from 1972 to 2004, there are two foundational elements to this: "One is love. The other is finding a way of coping with life that does not push love away.”
. . .
The conclusion? . . .
"The clearest message that we get from this 75-year study is this: Good relationships keep us happier and healthier. Period."
. . .
Because the data is clear that, in the end, you could have all the money you’ve ever wanted, a successful career, and be in good physical health, but without loving relationships, you won’t be happy. >>>more
Original Study records, from 1939:
Harvard Second Generation Study
Study of Adult Development The Study of Adult Development is a longitudinal study that has been following two groups of men over the last 80 years to identify the psychosocial predictors of healthy aging. We have two groups of participants: The Grant Study that is composed of 268 Harvard graduates from the classes of 1939-1944 and the Glueck Study group that is made up of 456 men who grew up in the inner-city neighborhoods of Boston. We are particularly interested in what psychosocial variables and biological processes from earlier in life predict health and well-being in late life (80’s and 90’s), what aspects of childhood and adult experience predict the quality of intimate relationships in late life, and how late life marriage is linked with health and well-being. We are now beginning to study the children of our original participants in our G2 (Second Generation) study.
Ongoing Projects
- Healthy Aging
- Marriage
- Social Neuroscience
1. Introduction
One of the main challenges facing medicine in these early years of 21st century is the foreseen ageing of the world population, and more specifically, the increase in the number of years spent in disability. These assertions are consolidated by the1st World Health Organisation (WHO) global report devoted to ageing (2015), which defines healthy ageing as a “process of developing and maintaining the functional ability that enables well-being in older age”. As stated by WHO general director Margaret Chan in the preface of the report, “healthy ageing is more than just the absence of disease; the maintenance of functional ability has the highest importance”.
The “healthy ageing” pathway corresponds to a lifelong process. After conception, the first and second parts of life appear to have the greatest influence on a person's functional trajectory, which has the potential at any time to become more or less positive. Building and maintaining intrinsic capacity, and living in functional independence within our own surroundings until the end of life is the most favourable outcome. >>> more
May 2016 The Mindspan Diet. By Preston Estep III, Ph.D., Ballantine Books/Random House
ABOUT THE MINDSPAN DIET
A comprehensive, easy-to-use guide to the foods that curb memory loss and improve cognitive longevity, this book will forever change how you think about diet and aging.
Even though people around the world are living longer than ever, but record numbers of us are experiencing cognitive decline and other brain disorders later in life. But there is good news: We now have the knowledge to extend both lifespan and mindspan, helping to ensure that our minds and bodies stay in peak form at any age.
Studying the diets of the populations that live longest with low levels of dementia, as well as the ways that certain food additives and ingredients interact with our genes, Dr. Preston Estep shatters myths about which foods are (and are not) beneficial to our brains, with simple changes you can make today to slow cognitive decline. Startling in its revelations about healthy eating for those over the age of fortyThe Mindspan Diet challenges us to rethink our approach to many common staples, including:
• Iron: While iron-fortified foods sound healthy, high iron intake can be toxic, especially for people over forty, and increases the risk of type 2 diabetes, Alzheimer’s, and Parkinson’s disease.
• Whole grains: Processed grains such as white rice, pasta, and flour are actually staples in the diets of cultures with the best cognitive health.
• Protein: Though it’s considered by some to be a miracle macronutrient, high levels of protein are actually hard on the kidneys, and may promote cancer and accelerate the progression of dementia.
Complete with food recommendations, shopping lists, advice on reading nutrition labels, and more than seventy delicious recipes, The Mindspan Diet shows that you can enjoy the richest flavors life has to offer and remain lean, healthy, and cognitively intact for a very long life.
Estep is the author of the 2016 book The Mindspan Diet, which proposes a concept called "mindspan" (a measure of overall health and mental longevity). Estep suggests that mindspan is superior to lifespan and other measures of health and longevity because a key parameter of mindspan is good mental function throughout life.[1] The Mindspan Diet presents a contrast between the longest lived people with high mental function ("the Mindspan Elite") and a second group of people from throughout the world who have good healthcare but shorter lives and the highest levels of cognitive decline ("the Mindspan Risk").
The book suggests that diet is a key difference and contrasts key dietary components and "biomarkers" (such as body weight and temperature, blood insulin and glucose, cholesterol, etc.) between Mindspan Elite and Mindspan Risk. The book concludes that a key difference between Mindspan Elite and Mindspan Risk is dietary iron, and the amount of iron in the bodies and brains of Mindspan Elite (low iron) and Mindspan Risk (high iron). A key finding of the book that is at odds with current dietary recommendations regards certain refined carbohydrate (carbs) foods. The book presents evidence that the base of the dietary pyramids of the Mindspan Elite is refined carbs in the form of white rice (mindspan leader Japan), and refined wheat pasta and bread (Mediterranean). Estep says that these foods in Mindspan Elite countries and regions are not enriched with iron, while equivalent foods in Mindspan Risk countries and regions are enriched with iron.
Longevity research
Estep is active in longevity and aging research and in criticizing anti-aging claims he suggests are unrealistic or poorly supported. He was the founding CEO and Chief Scientific Officer of TeloMe, Inc, a telomere analysis company and he is the former CEO of the human longevity research biotech company Longenity, Inc., which he founded with Matt Kaeberlein. Longenity folded but the company published research showing that a calorie restricted diet feminizes gene expression (in mice) and that it regulates both sirtuin and TOR aging regulatory pathways.[8]
He has been highly critical of strategies for engineered negligible senescence (SENS), a plan to reverse and repair the damage of aging. In mid-2006 he was the lead author of a submission by a group of nine scientists to the MIT Technology Review SENS Challenge.[9] The SENS Challenge panel of judges selected this submission as the best but concluded that it failed to meet the burden of proof established by the challenge: to show that "SENS is not worthy of learned debate." Some commentators have been critical of this requirement, saying that virtually any idea is worthy of some level of learned debate, though the terms of the prize were known in advance to all participants. Estep and colleagues failed to win the $20,000 prize on offer, but Technology Review's editor, Jason Pontin, nevertheless awarded them $10,000 for their "careful scholarship". (See the "De Grey Technology Review controversy" entry for more details.) Their submission criticized the SENS plan as essentially bringing Lysenkoism to modern aging research. Estep and colleagues donated the $10,000 award to the American Federation for Aging Research (AFAR).
Estep has been openly critical of SENS and of Aubrey de Grey for alleged misrepresentation of scientific evidence, and he suggests that the SENS plan does not address some of the most challenging aspects of aging including unrepaired DNA damage, noncancerous mutation and epimutation of the nuclear genome, and drift of cell and tissue-specific chromatin states. This latter damage type is generally considered a primary cause of cellular dedifferentiation and transdifferentiation, which degrade organismal function.
While critical of SENS and other anti-aging proposals, Estep is equally critical of the claim made by some in mainstream biogerontology that aging and/or death are incurable. He has challenged claimants to provide evidence for this assertion and points out the absence of evidence or physical law that might stand as a barrier to curing aging.[10] He appears to advocate mind uploading more strongly than attempting to conquer aging.[11] >>> more
"...removal of stagnant cells also showed a reverse in the signs of aging."
Senotherapeutics refers to therapeutic agents and strategies that specifically target cellular senescence, an altered cell state associated with ageing and age-related diseases. See more studies here
DHA:
Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized.>>> more
May 2015
Nature Regulating age research Hashizume, O., Ohnishi, S., Mito, T. et al. (2015),
Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Sci Rep 5, 10434 (2015).
Excerpt:
Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. See the study in NATURE (PDF): Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defect. >>>more
May 2015
New Atlas Japanese researchers reverse aging Researchers may have discovered fountain of youth by reversing aging in human cells
by Eric Mack New Atlas, May 27, 2015
Excerpt:
Professor Jun-Ichi Hayashi has found that the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging. "The issue may not be that mitochondrial DNA become damaged, but rather that genes get turned "off" or "on" over time. Most intriguing, the team led by Professor Jun-Ichi Hayashi was able to flip the switches on a few genes back to their youthful position, effectively reversing the aging process." >>> more
June 2011 Journal of Aging “Oral health behaviors help maintain natural, healthy and functional teeth but also appear to promote survival in older adults.” Dental Health Behaviors, Dentition, and Mortality in the Elderly: The Leisure World Cohort Study
Annlia Paganini-Hill, Stuart C. White, Kathryn A. Atchison
Journal of Aging, June 15, 2011
In the last decade the effect of oral health on the general health and mortality of elderly people has attracted attention. We explored the association of dental health behaviors and dentition on all-cause mortality in 5611 older adults followed from 1992 to 2009 (median = 9 years) and calculated risk estimates using Cox regression analysis in men and women separately. Toothbrushing at night before bed, using dental floss everyday, and visiting the dentist were significant risk factors for longevity. Never brushing at night increased risk 20–35% compared with brushing everyday. Never flossing increased risk 30% compared with flossing everyday. Not seeing a dentist within the last 12 months increased risk 30–50% compared with seeing a dentist two or more times. Mortality also increased with increasing number of missing teeth. Edentulous individuals (even with dentures) had a 30% higher risk of death compared with those with 20+ teeth. Oral health behaviors help maintain natural, healthy and functional teeth but also appear to promote survival in older adults. >>> more
Abstract
Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.
… Orthomolecular medicine is the restoration and maintenance of health through the administration of adequate amounts of substances that are normally present in the body. Nobel Prize winner Linus Pauling, one of the leading molecular chemists of the century, established this definition of orthomolecular medicine in 1968.
The aging process is typically accelerated as a result of free radical exposure, frequent or chronic inflammation, and toxic exposures (such as to heavy metals or industrial and agricultural hydrocarbons). Reversing this process or slowing it down is one goal of orthomolecular therapy, along with treatment of health problems.
An increasing number of scientific studies have been confirming the view that high doses of nutrients are therapeutic and preventive. Vitamins C and E, beta-carotene, B-complex vitamins, and coenzyme Q10 are among the many nutrients that have been shown to contribute positively to health and longevity at doses much higher than the RDA. While therapeutic levels for minerals, such as magnesium, zinc, and chromium, are much closer to the RDA, supplements beyond what is normally present in foods may still be essential for prevention and treatment of disease and slowing the aging process. >>>more
