We can never know absolutely and for sure whether doing the “right things” for our health will make a significant difference to our own healthy longevity. You have to wait and see, one chance to get it right, no going back to fix things up. We do, however, have a wealth of evidence that actions long commonly regarded as the “right things” for good health will indeed be good for our future healthy longevity. This evidence is quite separate from the comparatively recent investigations of medical science into the biochemical roots of good health and longevity.
What is this evidence? That wealthier, higher IQ people tend to live longer and suffer less age-related illness. For example:
Lower scores on measures of IQ at two time points were associated with [cardiovascular disease] and, particularly, total mortality, at a level of magnitude greater than several other established risk factors.
I don’t think that it’s ever been a grand mystery that regular exercise, a good physician relationship, and eating sanely are going to be good for you; the common wisdom for good health long predated the scientific studies showing that it was the case. The grand mystery is why so few people keep up with those efforts in their own lives, and suffer because of that negligence. I’ve been inclined to interpret results like the research above to mean that more intelligent people tend to get wealthier but also tend to do more of the right things for their health - you can be as rich as you like, but if you weren’t exercising all that time you were making money, you’re still going be at a higher risk for suffering cardiovascular disease at the end of the day.
Smarter people have a greater tendency to keep up with common sense health practices and gain a benefit by doing so. That’s my thesis. As to why that is the case - well, that gets back to what IQ actually measures, whether time preference is very different between individuals, and so forth.
Continue Reading December 31st, 2008
An item of interest on an otherwise slow day:
In this podcast, youll hear Dr. Platika review the accomplishments of the Pittsburgh Life Sciences Greenhouse, and hell talk about his new job: helping to get funding to study the world’s oldest people.
Dr. Platika is the chairman of the Supercentenarian Research Foundation, a new organization designed to raise funding for studies of supercentenarians, or people who have lived more than 110 years. Dr. Platika wants to know: Why have the very aged survived as long as they have? Are they less susceptible to the common diseases that slow down the rest of us? Ultimately, Dr. Platika hopes the foundation will contribute to the discovery of products that help people fight degenerative and other conditions associated with aging and maintain their mobility and quality of life.
The SRF has fairly close ties to the Methuselah Foundation, as I recall. Certainly, amyloidosis is a condition that interests both parties: a buildup of different types of clumping biochemicals in different tissues that leads to loss of function and eventually death. It is thought to be an important cause of death in supercentenarians who have evaded all the other common killers.
“The superseniors deviate from the norm not just in how long they live but in how they die,” says Coles, who arranges autopsies of the oldest old as part of his work with the recently established Supercentenarian Research Foundation. Only nine Supercentenarians have undergone postmortems - Calment, for example, never agreed to one - and Coles and colleagues have performed six of these procedures, including one earlier this year in Cali, Colombia, on a man who died at age 111.
Coles argues, based on these autopsies, that supers aren’t perishing from the typical scourges of old age, such as cancer, heart disease, stroke, and Alzheimer’s Disease. What kills most of them, he says, is a condition, extremely rare among younger people, called senile cardiac TTR Amyloidosis. TTR is a protein that cradles the thyroid hormone thyroxine and whisks it around the body. In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. “The same thing that happens in the pipes of an old house happens in your blood vessels,” says Coles.
The Methuselah Foundation is funding development of biomedical remediation as a technology platform to safely remove amyloid and other forms of aggregate from tissues, which should prevent that process from contributing to degenerative aging.
Continue Reading December 31st, 2008
Inflammaging is a term coined to describe one way in which the immune system runs awry with age. Like a malfunctioning thermostat, the level of inflammatory response is consistantly too high, leading to damage to aged tissue:
Inflammation is necessary to cope with damaging agents and is crucial for survival, particularly to cope with acute inflammation during our reproductive years. But chronic exposure to a variety of antigens, especially to some viruses such as cytomegalovirus, for a period much longer than that predicted by evolution, induces a chronic low-grade inflammatory status that contributes to age-associated morbidity and mortality. This condition carries the proposed name “inflammaging”.
I noticed a paper today which contains an interesting take on how inflammation leads to damage. It’s not just the inflammatory response, per this theory, but also the anti-inflammatory systems evolved to shut off an inflammatory response after it has served its purpose. If inflammation is constantly jammed on, then so is the anti-inflammatory system - based on the hormone cortisol - that is trying to shut it down. So you have at once all the downsides of both a constantly active immune system, and an immune system that is constantly damped down: damage from constant activity yet poor immune response when you do need it to fight off disease:
“Inflamm-aging” denotes the up-regulation of certain pro-inflammatory cytokines at older ages, and associated chronic diseases. It is well known that blood levels of cortisol also increase with age, an increase commonly considered to be due to activation of the Hypothalamus-Pituitary-Adrenal (HPA) axis by many non-specific stressors.
On the contrary, herein I describe how the activation of Hypothalamus-Pituitary-Adrenal (HPA), far from being unspecific, constitutes: a) the main specific response and counterbalance to “Inflammaging” (’anti-inflammaging’), b) an explanation for the well known paradox of immune-senescence: i.e. the coexistence of inflammation and immunodeficiency, as well as c) a complex mechanism of remodelling elicited by inflammaging, explaining the long and winding pathophysiological road that goes from robustness to frailty.
Indeed, the phenomenon of anti-inflammaging, mainly exerted by cortisol, with the passage of time becomes the cause of a marked decline of immunological functions, and its coexistence with the increased levels of pro-inflammatory cytokines of inflammaging, ultimately have negative impacts on metabolism, bone density, strength, exercise tolerance, the vascular system, cognitive function, and mood. Thus inflammaging and anti-inflammaging together determine many of the progressive pathophysiological changes that characterize the “aged-phenotype”, and the struggle to maintain robustness finally results in frailty.
The author points to cortisol, and if you look at the Wikipedia entry you will see touches upon a wide range of vital systems in the body. If inflammation is always on, then excess cortisol is constantly trying to turn it off, causing harm along the way.
Fortunately solutions to prevent the immune system from getting into this state in the first place are within sight. If the medical research community makes a sane shift from a philosophy of futile attempts to patch up the end results of aging to preventing and reversing specific degenerations earlier in life, then I imagine we’ll see a range of ways to restore a damaged immune system in the clinic by 2030. Have a look back in the Fight Aging! archives for some pointers:
Continue Reading December 31st, 2008
When compared to a random selection of folk in their middle ages and younger, centenarians have biochemistries that seem better adapted to long term survival. That makes sense, given that few of those random folk would make it to 100 under the same life circumstances as the centenarians. Hopefully researchers can use the identified differences to make faster progress in longevity science. Here is an example:
OBJECTIVES: To analyze several functions and antioxidant parameters of peripheral blood neutrophils from healthy centenarians (men and women) and compare them with those of healthy young (aged 25-35) and middle-aged (aged 65-75) men and women.
…
PARTICIPANTS: Twenty-one healthy centenarians (8 men), 30 young adults (15 men), and 30 middle-aged adults (15 men).
…
RESULTS: Neutrophil functions of the middle-aged group were worse than those of young adults and centenarians … The neutrophil functions of the centenarians were closer to those of the young adults. … With normal aging, total glutathione levels decrease, but the centenarians in this study showed levels similar to those of young adults. Centenarians showed the highest catalase activity of the three groups.
CONCLUSION: Progressive impairment of the immune system accompanies aging. The better preservation of function and antioxidant systems in the neutrophils of centenarians could play a key role in the longevity of these subjects.
The catalase data is interesting, given the work of Rabinovitch showing that increased catalase expression in mice - if targeted to the mitochondria - extends healthy life. It seems that there might be a fair degree of difference within the human species as to how genetically resistant people are to aging. For more on why catalase - an antioxidant - likely works to extend life when introduced to the mitochondria, you might look back into the Fight Aging! archives.
The catalase soaks up some portion of free radicals before they can attack your vulnerable mitochondrial DNA. Damage to this [DNA] leads to an unfortunate chain of events that causes entire cells to rabidly produce damaging free radicals and export them throughout the body. But stop a fraction of the original mitochondrial free radicals from attacking their birthplace, and you have slowed the rate at which one cause of aging happens - you have slowed down aging, and extended healthy life.
Continue Reading December 31st, 2008
Not to sound like a broken record, but the state of the mitochondria inside your cells is very important. The level of damaged suffered by these mitochondria is a determinant of your future health and longevity because of the further damaging processes set in motion by faulty mitochondria. Furthermore, we can point to some known ways to extend longevity - such as calorie restriction - and show that they cause changes in biochemical processes that act to eliminate damaged mitochondria before they cause significant harm or prevent that damage from occuring in the first place. As this recent abstract points out for one small facet of aging:
The mechanisms by which caloric restriction preserves skeletal muscle health with aging continue to be explored; however, mounting evidence points toward a convergence of effects at the level of the mitochondrion. Specifically, caloric restriction reduces mitochondrial reactive oxygen species production and promotes mitochondrial renewal via enhanced drive on mitochondrial biogenesis and autophagy.
The mitochondrial free radical theory of aging describes in detail how it is proposed that increasing numbers of damaged mitochondria lead to the slow breakdown of systems within the body. A crucial point here is that each of your cells contains thousands of mitochondria, a population constantly in flux with members being broken down when damaged and replaced through binary fission of remaining mitochondria, dividing in two like bacteria. Mitochondria have their own internal DNA, separate from nuclear DNA in your cells, and when that mitochondrial DNA gets damaged then every future generation of mitochondria carry the damage with them.
The core of the mitochondrial free radical theory of aging is an explanation as to how certain forms of mitochondrial DNA damage, such as large deletions, can subvert the normal processes that check for damaged mitochondria to recycle. These damaged mitochondria will be recycled more slowly than their pristine counterparts and will thus soon replicate unchecked to take over the entire mitochondrial population of a cell. Things start to go downhill for that cell and all other nearby cells soon thereafter as the mechanisms of metabolism run awry. Here is a paper providing solid evidence for that concept:
Age-dependent accumulation of partially-deleted mitochondrial DNA (DeltamtDNA) has been suggested to contribute to aging and the development of age-associated diseases including Parkinson’s disease. However, the molecular mechanisms underlying the generation and accumulation of DeltamtDNA have not been addressed in vivo.
In this study [we] obtained in vivo evidence that DeltamtDNAs with larger deletions accumulate faster than those with smaller deletions, implying a replicative advantage of smaller mtDNAs. These findings identify DSB, DNA repair systems and replicative advantage as likely mechanisms underlying the generation and age-associated accumulation of DeltamtDNA.
More damage means more replication of damaged mitochondria. This isn’t all idle research, of course: having identified damage to mitochondrial DNA as a significant contributer to degenerative aging, there are a wealth of potential ways to reverse or eliminate it through medical science, some already demonstrated in laboratory animals. Look back in the Fight Aging! archives to see some of them:
Continue Reading December 31st, 2008
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