Dear Future Centenarian,
It takes a lot of things to navigate the pitfalls of life.
Brains, guts, good people skills, a bit of luck, vast amounts of energy and drive…
... and the kind of motivation that kicks you in the butt every morning.
Yes, all of that stuff, and more.
But the PRIMARY thing you need to be a winner (which I define as successful and happy) is this: You gotta be healthy.
All the popularity, friendships and possessions in the world won't do a thing for you, if you're gasping for breath and rotting from the inside.
The foundation of everything you go after (and you should have ridiculously large longevity goals at all times) is simply…
... being a good animal.
That means taking time every single day to maintain, nurture and groom your entire body and soul. Like every animal in the wild does.
Learn to breathe deeply, so carbon dioxide doesn't build up in your lungs. (An hourly exhaust check does the trick, but you must be diligent.)
Eat fabulous fuel-laden food most of the time. (And use pizza and burgers as rare treats, not basic sustenance.)
Meditate like your entire future depends on it. Every day, for at least twenty minutes, zone out and let your brain float in its own juices. It's a natural way to recharge the battery and flush out toxic thoughts. (I need more work in this department.)
Feed your soul, too. However you want to approach your spiritual side is just fine… but it must be done.
You're not just a mass of chemical and mechanical chain reactions. There's an essential life force within you (within all of us) that shrivels when ignored.
And of course… regular cardio and resistance training. Exercise with gusto and purpose. Your dog knows all of these tricks — he stretches with pleasure, runs and cavorts with joyous abandon, eats and pees and sleeps with unabashed bliss.
Be more like your dog, and rewards await. (Okay, leave out the more gross stuff he does, but try to maintain the suppleness and grace of his existence.)
Yes, we all “may” die at some point.
But in the meantime, chew up some scenery and live large. Key word: Live. Like a healthy, gleeful beast...
Thank you for your inspiration John Carlton.
Cancer Survivors have Double the Risk of Suffering a Later Stroke
Surviving cancer comes with a well-known loss of remaining life expectancy, roughly the same as being obese or a lifelong smoker.
It is plausible that this is a consequence of the generation of large numbers of lingering senescent cells, resulting from radiotherapy and chemotherapy, still the dominant forms of cancer treatment.
Calorie Restriction as a Way to Slow Harmful Age-Related Changes in the Gut Microbiome
The practice of calorie restriction, eating 20-40% fewer calories while still obtaining an optimal intake of micronutrients, produces sweeping changes in the operation of cellular metabolism.
It improves health and extends life span in near all species tested to date, though much more so in short-lived species than in long-lived species. The most important mechanism appears to be a boost to the operation of the cellular housekeeping processes of autophagy, more efficiently clearing out damaged components and unwanted molecular waste before they can cause further issues.
That said, near every measure of aging is slowed by calorie restriction, so it is no surprise to see in today's open access paper that this slowing also applies to the detrimental changes to the microbial populations of the gut that are observed to take place with age.
Ways in Which the Failing Lymphatic System Contributes to Age-Related Disease
The lymphatic system is a parallel circulatory system responsible for moving fluid, immune cells, and a range of vital molecules around the body.
It is of particular importance to immune function, allowing components of the immune system to carry messages from place to place in the body, and communicate and coordinate the immune response at the hubs known as lymph nodes.
Like all tissues in the body, the lymphatic system is negatively impacted by aging, and this has widespread detrimental effects throughout the body and brain.
Corpora Amylacea in the Clearance of Metabolic Waste from the Brain via Cerebrospinal Fluid Drainage
Age-related neurodegeneration is characterized by rising levels of various protein aggregates in the brain. A few of the many thousands of proteins in the body can become misfolded in ways that encourage other molecules of the same protein to also misfold in the same way, forming structures that spread and precipitate into solid deposits.
These aggregates are accompanied by a halo of surrounding biochemistry that is toxic to neurons, disrupting function in the brain and killing vital cells, causing loss of cognitive function and ultimately death.
A Large Study of Aspirin Use Finds Reduced Mortality, Contradicting the Recent ASPREE Study Results
The back and forth over whether regular aspirin use is beneficial continues with the publication of results from analysis of a large patient population that show a 15% reduction in all-cause mortality in patients using aspirin.
This contradicts the much smaller (but still large in and of itself) ASPREE clinical trial, in which patients using aspirin exhibited a small increase in mortality in comparison to their peers. As in that earlier study, the data here strongly suggests that benefits and risks vary with patient characteristics, such as whether or not a patient is overweight.
Low Lymphocyte Levels Correlate with Greater Mortality in Late Life
Lymphopenia is the condition of having lower than normal levels of lymphocytes, a mix of cells of the adaptive and innate immune system, in blood samples.
The immune system is of vital importance to health, and this is demonstrated here by data that shows raised mortality in the sizable fraction of older people with degrees of lymphopenia versus those without.
Lymophocytes do not just respond to the presence of infectious pathogens, but also attack and destroy senescent cells and cancerous cells, among other important activities. A severely deficient immune system is a real threat to life, and as this work illustrates, even a modestly deficient immune system is something to worry about.
The near future should see the advent of approaches to restore immune function in the elderly.
Are Benefits from Cardiac Stem Cell Therapy Due to an Immune Response to Transplanted Cells?
As this article notes, researchers have recently suggested that the benefits to heart function observed over many years of stem cell therapies are not in fact due to any action of the cells themselves, not even cell signaling mechanisms such as release of exosomes, but are rather due to an immune response to the transplanted cells.
The study reported here illustrates the point by showing some degree of regeneration of injured heart tissue to take place in mice when the debris of dead cells is transplanted. We might compare these findings with the body of work showing that delivery of exosomes can spur cardiac regeneration; few portions of the field of stem cell therapy are lacking a good supply of contradictory evidence.
Investigating Circular RNAs in Cellular Senescence
Numerous demonstrations of rejuvenation via clearance of senescent cells in recent years have led to a newfound and considerable enthusiasm for the study of the mechanisms of cellular senescence. Ever more funding in flowing into this part of the life sciences.
That any new discovery might lead to a company, valuable intellectual property, a means to treat aging, is a considerable incentive for the various research and funding ecosystems. The open access research noted here is a representative example of numerous projects presently underway.
Proteasomal Failure as a Contributing Cause of Protein Aggregation in Neurodegenerative Disease
Neurodegenerative diseases are characterized by the formation of protein aggregates, misfolded proteins that encourage other molecules of the same protein to also misfold in the same way, forming solid deposits that damage and destroy brain cells.
Researchers here suggest that the age-related decline in proteasomal function is a contributing factor. The proteasome is a structure that breaks down damaged or otherwise unwanted proteins in cells.
Reviewing the Present Development of Biomarkers of Aging
As this open access paper notes, a great deal of the present work on developing biomarkers of aging involves machine learning. Researchers are sifting and arranging health metrics, blood markers, and epigenetic data to find combinations that predict risk of disease and mortality.
The aim at the end of the day is to determine a good measure of biological age, one that accounts for all of the burden of cellular and molecular damage that leads to death and dysfunction, and will thus be a good, rapid measure of effectiveness for rejuvenation therapies.
The biggest challenge in this line of work at the present time is that researchers don't have a good understanding of what exactly is being measured by many of these potential biomarkers. It is entirely plausible that they are only a measure of some types of the underlying damage of aging, and will thus be of no use in assessing many of the possible approaches to rejuvenation.
A Survey of Existing Literature on Senescent Cell Burden by Age and Tissue in Humans
Cells enter a state of senescence in response to reaching the Hayflick limit, or to a toxic environment, or potentially cancerous mutational damage.
Near all senescent cells self-destruct, or are destroyed by the immune system. Some linger, however, and when present in even comparatively small numbers relative to normal cells, these senescent cells cause considerable harm via their inflammatory secretions.
Thus the targeted destruction of senescent cells via senolytic therapies has been shown to extend healthy life and reverse numerous aspects of aging in mice. Human trials of senolytic treatments are presently underway, and have produced promising initial results.
Variation in Early Life Stress Contributes to Differences in Lifespan in Genetically Identical Worms
Why do genetically identical nematode worms raised in the same environment exhibit a distribution in life span? Researchers here suggest that differences in oxidative stress in early life are an important contributing factor, perhaps steering metabolism in some of these simple organisms towards greater resistance to the rising oxidative stress of aging.
Assessing Late Life Cardiovascular Risk from Mid-Life Cholesterol Levels
Researchers here use data on cholesterol and health assessed in a large patient population over a 40 year period in order to determine how the risk of suffering atherosclerosis by age 75 varies with cholesterol levels assessed in the 30s and 40s.
It is no surprise that higher cholesterol levels mean a greater risk of atherosclerosis, the development of fatty lesions that narrow and weaken blood vessels. The condition is one in which the macrophage cells responsible for removing these unwanted lipids from blood vessel walls are made dysfunctional by rising levels of oxidized cholesterol. The more cholesterol in the blood stream, the more oxidized cholesterol, all other things being equal.
Clearance of Senescent Cells is Fast in Youth, Slow in Aging, Tipping the Balance Towards Accumulation
The accumulation of senescent cells is a cause of aging, which is why a great deal of effort is presently going towards the development of senolytic therapies capable of selectively destroying these unwanted cells.
Very little is known about the dynamics of senescent cells in old age, however. We know that older individuals have more senescent cells at any given moment in time, but is this because a small fraction of the many senescent cells created every day manage to linger persistently for years, resistant to the efforts of the immune system to remove them, or because clearance processes, while they will eventually destroy all senescent cells, are slowed to the point at which they cannot keep up?
A Review of Efforts to Target Senescent Cells in Order to Treat Age-Related Disease
This review paper looks at the present range of strategies adopted by the research and development communities in their efforts to target senescent cells. The accumulation of senescent cells is a contributing cause of aging; many animal studies have demonstrated reversal of aspects of age-related disease via clearance of senescent cells, particularly for those conditions in which chronic inflammation plays an important role.
Senescent cells are comparatively few in number even in later life, but cause harm via secreted signals, a potent mix of proteins and vesicles known as the senescence-associated secretory phenotype (SASP). The SASP drives inflammation, changes the behavior of nearby cells for the worse, and destructively remodels surrounding tissue.