Common Sense on Aging and the Role of Medicine
Ronald Bailey, who has written on and off on the topic of longevity science for about as long as I've been paying attention to the subject myself, here outlines a common sense view of aging and its treatment as a medical condition. It is a sign of progress that more people are stepping up to make reasoned arguments along these lines. At the large scale and over the long term, the only research that is carried out to completion is that which is supported and understood, at least in outline, by the public at large. Lines of research that aim to control the causes of aging and thereby prevent and cure all age-related disease are not yet widely supported or appreciated, and this is why such research is still a minority concern in the scientific community. There is much work left to be done for patient advocates.
In the 21st century, almost everything that kills people, except for accidents and other unintentional causes of death, has been classified as a disease. Aging kills, so it's past time to declare it a disease too and seek cures for it. In 2015, a group of European gerontologists persuasively argued for doing just that. They rejected the common fatalistic notion that aging "constitutes a natural and universal process, while diseases are seen as deviations from the normal state." A century ago osteoporosis, rheumatoid arthritis, high blood pressure, and senility were considered part of normal aging, but now they are classified as diseases and treated. "There is no disputing the fact that aging is a 'harmful abnormality of bodily structure and function,'" they note. "What is becoming increasingly clear is that aging also has specific causes, each of which can be reduced to a cellular and molecular level, and recognizable signs and symptoms."
So why do people age and die? Basically, because of bad chemistry. People get cancer when chemical signals go haywire enabling tumors to grow. Heart attacks and strokes occur when chemical garbage accumulates in arteries and chemical glitches no longer prevent blood cells from agglomerating into dangerous clumps. The proliferation of chemical errors inside our bodies' cells eventually causes them to shut down and emit inflammatory chemicals that damage still healthy cells. Infectious diseases are essentially invasions of bad chemicals that arouse the chemicals comprising our immune systems to try and (too often) fail to destroy them.
Also in 2015, another group of European researchers pointed out that we've been identifying a lot of biomarkers for detecting the bad chemical changes in tissues and cells before they produce symptoms associated with aging. Such biomarkers enable pharmaceutical companies and physicians to discover and deploy treatments that correct cellular and molecular malfunctions and nudge our bodies' chemistry back toward optimal functioning. As a benchmark, the researchers propose the adoption of an "ideal norm" of health against which to measure anti-aging therapies. "One approach to address this challenge is to assume an 'ideal' disease-free physiological state at a certain age, for example, 25 years of age, and develop a set of interventions to keep the patients as close to that state as possible," they suggest. Most people's body chemistry is at its best when they are in their mid-twenties. In fact, Americans between ages 15 and 24 are nearly 500 times less likely to die of heart disease, 100 times less likely to die of cancer, and 230 times less likely die of influenza and pneumonia than people over the age of 65 years. For lots of us who are no longer in our twenties, television talk show host Dick Cavett summed it up well: "I don't feel old. I feel like a young man that has something wrong with him."
Link: http://reason.com/archives/2016/12/02/time-to-declare-aging-a-disease-and-get
Hi,
"...As a benchmark, the researchers propose the adoption of an "ideal norm" of health against which to measure anti-aging therapies. "One approach to address this challenge is to assume an 'ideal' disease-free physiological state at a certain age, for example, 25 years of age, and develop a set of interventions to keep the patients as close to that state as possible," they suggest. Most people's body chemistry is at its best when they are in their mid-twenties. In fact, Americans between ages 15 and 24 are nearly 500 times less likely to die of heart disease, 100 times less likely to die of cancer, and 230 times less likely die of influenza and pneumonia than people over the age of 65 years. For lots of us who are no longer in our twenties, television talk show host Dick Cavett summed it up well: "I don't feel old. I feel like a young man that has something wrong with him."
This.
This is exactly IT. I don't understand why it has not been more pushed - everything pointed to that. 200 to 500 times less likely to die at 20 - These numbers are Humongously Revealing.
I feel sad, reading the last line because there is no hope for people above 40-50, I mean beyond making them reaching 120-130 tops maximum lifespan. They've accumulated too much damage already and their epigenetic signature (that of plus 50s) is way 'too off (way too drifted to bounce back, we can't bring them back to '20 biological age')'. It could be possible to revert by retroprogramming their DNA methylation/epigenetics but the accrued damage accumulation would be a problem - as some of these damages are irreversible chemical reactions (that's the big problem). Still, there is still much ambiguity about wether it is truly 'irreversible' and cells have delevopped ways to get around that (such as cell cycling damage dilution, but many somatic cells are non-cycling/non-mitotic so that's another problem plus most of these Junk are in ECM as cross-links, lipofuscin, drusen, ceroid, amyloid, AGEs, etc). It's why we can perfect scarless Healing when fœtus is injured while adult skin makes granulation and scar formation. What we think may be irreversible, could in fact, by some epi/genetic mechanism or unknown mechanisms be reversible. I wouldn't hold my breath on it though; so far, it's mostly irreversible and as such, aging continues its course (for those over 50, thus, it mostly is a natural limit of 120-130s tops with all the SENS Tools and thérapies chimed in (better than dying at 90, at least it gives an extra 30 'reasonably' healthy years (should SENS actually, really, work)).
A lot of the SENS therapies target so called irreversible damage.
Also, generally speaking a lot of the damage to the extracellular matrix and post mitotic tissues can be fixed by replacement.
I know everyone expects life extension to come in the form of pills, and sure, I agree it's not ideal but in the nearest future it's going to be in the form of surgery more likely than not.
I'm not sure it will ever be completely free of surgery or some other invasive procedure if I have to be honest.
@Anonymoose: Of the seven categories, I think only repleniSENS will need surgery. I can't see how surgery can be needed for the others.
@CANanonymity: I'm 42 and I think that the Methuselarity will come in time for me, even at the current level of funding. Indeed, I think we will have the first SENS therapy in a couple of years (probably from Unity).
I'm 40-ish as well and not too worried about being too old to be saved. More and more of the currently irreversible damage will be reversible as time goes on, and each new step will buy more years. Though it's a game of probabilites of course, and some people do get cancer in their 40s (or even earlier) and so on, but that's fairly unlikely, esp with a healthy lifestyle. So I remain hopeful, let's beat this thing.
BTW, there is a new senescent cell company doing crowdfunding on lifespan.io.
@Antonio: I know; I have an interview post with CellAge scheduled for Friday.
"...so far, it's mostly irreversible and as such, aging continues its course (for those over 50, thus, it mostly is a natural limit of 120-130s tops with all the SENS Tools and thérapies chimed in (better than dying at 90, at least it gives an extra 30 'reasonably' healthy years (should SENS actually, really, work))."
Hi CANanonymity,
If that damage becomes reversible in the future (it will be step by step), I don't see why even those over 50 now wouldn't get a chance to return to a youthful-like state. Are you implying there is some threshold above which damage becomes irreversible, no matter future advances in rejuvenation technology? As to epigenetic regulation, it's still unclear to me how it all relates to damage or what is causing these changes in expression patterns. Can damage in a way cause expression patterns to change in such a way that we observe in aging cells? Is there any scientific hint WHY these expression patterns change with age?
Hi K., Anonymoose and Antonio, Thanks for that,
@K.
Yes, exactly, I too am (bordering) on this opinion - but somehow I have feeling damages are only part of the equation. As there can be aging - and no damage visible (i.e. cell cycling arrest with no oxidative challenges/dna damage whatsoever - it means is a complex (epi)genetic/transcription/gene expression program that works in tandem with damage (For example, there are 3 main senescene pathways (Replicative Senescence (by cell cycles count), Oncogene-induced Senescene (by p53/p16/p21) and Spontaneous/Premature 'Stress-induced' Senescence (seen by inflammation causing it spontaneously)). Damage work in tandem with it but it's only part of it. Calorie Restriction shows reduction of all types of damages and thus, lifespan extension of certain animals. Is it - It - that's It ? Doubtful, it's more complex than that CR is capable of altering DNA methylation, different insulin pathways (IGF/PK3/mTOR/SIR/Cyclins/p53/p16 oncogenes who accelerate senescence..etc..), redox thiols (all those antioxidant response pathways like ARE/Nrf2/etc and gene expression is so many levels (I think CR acts on some 500,000 genes all the same time!). That is more it, and then damages are altered too (accumulation/accrual speed). It's more complicated that we thought sadly (and why is there is So Much Discrepancy in study results (Who's suppose to be right ?), it's almost as if you can redo the lab study and get new results if you change one tiny thing - it's over; it doesn't work anymore).
I'm not implying there is a threshold before it's irreversible but things seem to point to that. Normally speaking these epigenetic changes should be reversible when the damage would be removed (...should...)/when we retro-reverse the 'irreversible', but it may not turn out that way (that'S like why anti-oxidant therapies failed miserably; we think we know but not entirely it seems), It should and really hope it does (So far I've been surprised many times in wrong way - where it was 'obvious' but instead it was the total opposite that happened. I fear this will happen here). There so many stumbling blocks ahead of us that we are in it for many new 'surprises'.
'' As to epigenetic regulation, it's still unclear to me how it all relates to damage or what is causing these changes in expression patterns. ''
External forces (and mostly also cell cycling replicationg passages (replicative end problem Hayflick)...environment, life style changes, stress, etc...they modify 'the trajectory' and create 'epigenetic drifting' (also called transcription infidelity). These external 'stimulis' if you will act 'as forces' to act on your genes creating an epigenetic signature that is yours and constantly changing - creating a very 'you' (and no body else) phenotype. How is relates to damages is because these epigenetic changes (through methyl loss or addition) 'activate' or 'keep silent' (gene silencing) important anti-inflammatory and inflammatory genes (especially in the immune system category). They can then proceed to 'inflamme' (such IL-6, INF-g, TNF-a and cytokines) or anti-inflamme (Interleukin-10), this causes production of vasts amount of ROS (reactive oxygen species) and their products (lipid peroxides, hydroperoxide, hydroxyl radical, H2O2, etc...down the chain to Advanced Glycation Products like CML, carbonyls or aldéhydes (MDA/TBARS) formation that fragment the DNA (single/double strand breaks). Also damaging the mitochondria (cell's energy ATP production) by appearance of mitochodrial Lesions and dysfuncionning Complex I-V on the innermembrane.
So Tons of 'Great Things...happening all by your epigenetic transformation and programm 'happening' and contributing to damages.
''Can damage in a way cause expression patterns to change in such a way that we observe in aging cells? Is there any scientific hint WHY these expression patterns change with age?''
Exactly, yes, on first question.
Last question, because it is a 'morphing thing/a transformative/self-adaptive process' by so many factors (like epigenetic drifting, transcription loss, oxditive lesions, damage Junk everywhere, all of these Signal and Affect the GEnome - that affect each other 'giving a 'random number'' 'luck (centenarian) or unluck (progeria) of the lotto-draw'' if you will (it's the whole pleiotropic antagonistic hypothesis/randomness of thermodynamic law/chemical processes/the entropy thing too). But, I believe we will be able to revert them - methylation/epigenetic is very powerful science because by a 'on/off' switch mechanism (methyl presence), and thus, we could revert back to 20 years old.
Just a 2 cent (I'm not researcher or anything, just curious like all : ).
@Reason: Heh, I did assume you had a post in the making :)