Aging, because beautiful old people are works of art

@Marina T Alamanou
Dec 2 · 12 min read


Aging (spelled ageing in British English) is a constant reminder of the passage of time and its purpose is a question that has intrigued and puzzled scientists for centuries. Aging is the process of becoming older, that involves a series of functional changes that appear over time and are not the result of illness or accident but occur as the result of accumulating disorders in the body’s structure and functions. It is an unpreventable chronological, social and biological process and is genetically determined and environmentally modulated.

For example the longevity gene INDY (for I’m not dead yet) has been discovered that helps determine the life-span of the fruit fly Drosophila. When the gene is mutated, it can double the life-span of Drosophila. It appears that the protein encoded by INDY transports and recycles metabolic byproducts. Defects in the gene may lead to production of a protein that renders metabolism less efficient so that Drosophila appears to dieting, even though its eating habits haven’t changed. Mutations in Indy thus appear to create a metabolic state that mimics caloric restriction (environment), which has been shown to extend life-span.

Basically, different people or different cultures, age at different rates and some tend to age more gracefully than others simply because of their genes and their environment. But aging is also about time and time perception. Time perception is a construction of the brain. How fast we perceive time to be passing — or “mind time” — can be manipulated or distorted, with our evaluations of time based on our state of being at the time of judgment (i.e. five minutes can be perceived as eternity or just seconds depending on how we feel). So, could how we age and how long we live depend on time perception?

But what is time?

Past, present and future coexist. “Now time” explained easily.

Time is the indefinite continued progress of existence and events that occur in an apparently irreversible succession from the past, through the present, to the future. But, while most people think of time as a constant, physicist Albert Einstein showed that time is an illusion. Also according to theoretical physicist Carlo Rovelli, passing time is an illusion: our naive perception of its flow doesn’t correspond to the physical reality. Basically, more and more physicists believe that past, present and future coexist. They believe that “every moment is co-creating every other moment both forward and backward in time”, meaning that the past influences the future and the future influences the past in a endless feedback loop.

So, if “passing time is an illusion”, “time perception is a construction of the brain”, and “every moment is co-creating every other moment both forward and backward in time”… can we say that our only way out of this loop is by influencing our “future” with thoughts of longevity (i.e. Can I live to be 150?), that would eventually change our “future (present at the time and also past for the future)” to “accept” a mutation that will change our perception of time and therefore change our future and past…so we can live longer?!? In the end, its just a mind game and if you think about it past, present and future actually do coexist. It is just our brain that defines a chronological order and accepts a life span of 70-85yrs as normal. And as Søren Kierkegaard beautifully stated If you name me, you negate me. By giving me a name, a label, you negate all the other things I could possibly be”.

Anyway, leaving behind us this endless loop of time (whatever time is) and going back to aging, your chronological age (number of years that have passed since you were born or trips you’ve made around the sun) can differ significantly from your actual biological age (how well you’ve held up during those trips). The biological age, regardless of how many years ago you were born, occurs as you gradually accumulate damage to various cells and tissues in the body. Additionally, your chronological age, and even your biological age, may differ considerably from your functional age, the apparent age based on your functional capabilities in day-to-day activities. Functional age is sometimes considered to comprises four different dimensions: chronological, biological, psychological and social.

Apparently, the fact that chronological, biological and functional age can differ so much is probably the indication that the process of aging can be “manipulated” in relation to time, or genes or environment or all together. And this “manipulation” creates a gap where lies our ability to change aging and time perception. In fact, between stimulus (how long are you going to live?) and response (I am gong to live 150 yrs) there is a gap. In that gap is our power to choose our response (Viktor E. Frankl). In our response lies our growth and our freedom from the physical constraints of our physical reality.

Aging Journey

So, let’s begin this fascinating journey of aging by looking at what is happening inside our cells by following the nine hallmarks of aging that will give rise eventually to different aging dependent pathologies.

1) As we grow old an accumulation of genetic errors due to genomic instability (high frequency of mutations) are accumulating in different parts of our body.

Hallmarks of Aging: Genomic Instability

Naturally occurring DNA damages due to endogenous cellular processes are very frequent in the genomes of human cells, for example 10,000 oxidative damages per cell, per day can take place. But is the reduced DNA repair ability the important source of genome instability, that would eventually bring cancer, neurological and neuromuscular disorders.

So, search for offers and sequence your self. For exapmle in 2018 Cambridge-based Veritas Genetics lowered its $999 whole genome sequencing and interpretation service for just $199 for two days, or to the first 1,000 people who buy its kits.

2) As we grow old size actualy does matter, so telomere degradation is your enemy.

Telomeres: protect your cells from aging, until they get very short that they can no longer protect the cell

Telomeres, the nucleotides that live at the end of chromosomes, are in charge of how quickly cells age and eventually die and they are one of the most on the spot indicators of a person’s biological age.

In a report published in 2018, researchers found that very short telomeres characterise diseases such as pulmonary fibrosis or primary immunodeficiency and bone marrow failure and at least 5,000–10,000 Americans have disorders related to short telomeres (leukemia). The qPCR to test your telomeres costs about $100. For example Telomere Diagnostics sells a $99 at-home blood-testing kit that tells customers the average length of their telomeres.

3) Epigenetic alterations — genes are turned on or off by changing the chemical structure (methylation) of DNA but not changing the DNA coding sequence — have been shown to be correlated with many human diseases, including different cancers, autoimmune disorders, neurological disorders Fragile X syndrome as well as Huntington, Alzheimer, Parkinson diseases and schizophrenia.

The epigenetic clock — a test based on DNA methylation levels — can be used to measure age and is a promising biomarker of aging and can accurately predict human chronological age. The epigenetic clock leads to a chronological age prediction that has a Pearson correlation coefficient of r=0.96 with chronological age (close to its maximum possible correlation value of 1).

A New York City based biotech startup Elysium Health offers a ($500) at-home saliva test called Index, claiming it can help you figure out your biological age by looking at DNA methylation. Currently, their test only offers basic information on biological age — a kind of overall health score. Moreover, according to a recent study made public in International Journal of Cancer in 2018, an epigenetic-based test can beat Pap & HPV test for detecting cervical cancer.

Bovine pulmonary artery endothelial cells stained for actin (pink), mitochondria (green) and DNA (yellow)

4) Aging comes also with mitochondrial dysfunction that brings lack of ATP (energy).

As you age your mitochondria — that is the powerhouses of your cells — start to decline as well. While taking your tablets of coenzyme q10 is a wise thing to do, genetic testing is another option.

Genetic testing often begins with analyzing the mitochondrial DNA and testing also the nuclear DNA for genes known to be involved in mitochondrial diseases. If these tests come up negative, your nuclear DNA may need to be completely analyzed through whole exome sequencing (this is similar to whole genome sequencing, but analyzes just the genes that code for proteins). Additional, non-genetic tests include: biochemical tests on urine, blood and spinal fluid, muscle biopsy to examine the mitochondria and test enzyme levels and magnetic resonance imaging (MRI) of the brain and spine.

Telomere damage, epigenetic dysregulation, DNA damage and mitochondrial dysfunction are primary drivers of damage in aging, that can induce senescence. Senescence can in turn drive aging in response to damage: stem cell exhaustion and chronic inflammation. Other responses to damage, such as proteostatic dysfunction and nutrientsignaling disruption, are also integrally linked with the senescence response

5) Cellular senescence and immunosenescence.

Normally the body removes the problematic cells with genetic errors via apoptosis in conjunction with the immune system. Unfortunately, some cells evade apoptosis, taking up space in the tissue and pumping out inflammatory signals that damage the local tissue. These cells are known as senescent cells.

Senescent cells they secrete pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which together form the SASP (senescence-associated secretory phenotype). The SASP is thought to significantly contribute to aging and cancer; thus, senolytics (a new class of drugs for the destruction of senescent cells) and the removal of the SASP are a potential strategy for promoting health and longevity. It was also discovered that senescent cells have increased expression of pro-survival genes consistent with their resistance to apoptosis, so drugs targeting these pro-survival factors selectively killed senescent cells. Two such drugs are dasatinib and quercetin, which are both able to remove senescent cells.

6) Another thing to “control” during aging is the mechanism in charge of quality control for protein synthesis (proteostasis).

Proteostasis means that we have biological pathways within our cells that control the biogenesis, folding, trafficking and degradation of proteins. Any dysfunction in proteostasis can arise from errors in any of the above steps. For axample: Two major pathways of protein degradation have been described in eukaryotic cells: 1) the ubiquitin-proteasome system (UPS), responsible for degrading 80–90% of proteins and 2) autophagy, primarily responsible for the degradation of most long-lived proteins, but also for aggregated proteins as well as cellular organelles.

The decline in quality control of protein degradation can give raise in more than 50 diseases including cystic fibrosis, Huntington’s disease, Alzheimer’s disease, lysosomal storage disorders, senile systemic amyloidosis, liposarcoma, fibroma and others. Scientists have been working for years to develop drugs that can regulate this process.

For example lithium — used widely as a mood-stabilizing drug for the treatment of bipolar disorder — was shown to induce autophagy and reduce mutant huntingtin aggregates and cell death in Huntington’s disease. Moreover, pathology markers such as serum amyloid A or beta amyloid in cerebrospinal fluid are indicators of chronic inflammation or Alzheimer. So check your self.

Nutrient sensing

7) Nutrient sensing — cells ability to recognize and respond to fuel substrates such as glucose — is also gradually declining as you age.

The insulin and IGF-1 signaling pathway (glucose homeostasis) is a critical aging mechanism. Current evidence indicates that increased nutrient signalling accelerates aging, and decreased nutrient signalling, achieved with caloric restricted diets or by stimulation of sirtuins (activating sirtuins with NAD+ precursors), promotes healthspan and longevity. Metformin (also known as Glucophage) — a cheap, generic drug to treat type 2 diabetes — has emerged as a possible drug for promoting longevity. The mammalian target of rapamycin (mTOR) complexes are the most relevant downstream effectors of the insulin and IGF-1 signaling pathway for longevity. So, life science company named Emtora Biosciences is trying to inhibit the age-signaling pathway mTOR. ERapa its new formulation of the drug rapamycin — which was initially developed as an immunosuppressant to prevent organ transplant rejection at a high dose — it is now believed that a low dose might rejuvenate humans.

8) The decline in regenerative capability of different tissues with aging, along with a significant reduction in the number, proliferative capacity, or differentiation potential of distinct stem cells, has led to the idea that aging is due, at least in part, to the loss of functional adult stem cells needed for tissue repair. But while drinking blood from young donors, might not be such a good idea, startups’ goal to mass produce stem cells that can change the face of regenerative medicine is a healthier alternative for the future.

9) Altered intercellular communication is another of the integrative hallmarks of aging, but is mainly caused by other hallmarks, particularly cellular senescence and inflammation.

Increased inflammation across the body leads to cells increasingly activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in their nuclei which regulates inflammation. When NF-kB is activated in the hypothalamus, it has been shown to inhibit the production of gonadotropin-releasing hormone (GnRH). This hormone is used to signal other bodily systems, and its reduction may contribute to bone fragility, muscle weakness, skin degradation, and other harmful effects with age. This activation of NF-kB and the inhibition of GnRH, is thought to contribute to a variety of age-related diseases. Therefore, treating this hallmark may have a wide-ranging impact on health and disease in old age.

Moreover according to a paper co-authored by Irina Conboy, blood from older creatures can be harmful to younger creatures, perhaps due to harmful signals used for intercellular communications within the old blood. As she explained, a route that is being explored to treat this hallmark is apheresis, in which the pro-aging signaling molecules are removed once the blood is removed from the body, and then the blood is reintroduced; this is an attempt at mimicking the effect of parabiosis. Which sounds a good idea.

In the meanwhile if you want to stay young try the 13 most anti-inflammatory foods you can eat: berries, fatty fish, broccoli, avocados, green tea, peppers, mushrooms, grapes, turmeric, extra virgin olive oil, dark chocolate and cocoa, tomatoes and cherries.

And Finally a Drug Cocktail that Reverses Aging: the curious case of Benjamin Button

The results of a minor de-aging clinical study in California were just published in the journal Aging Cell and suggest that for the first time ever may be possible to reverse the body’s biological epigenetic clock.

Nine healthy participants were given a mixture of three common drugs (growth hormone and two anti-diabetic drugs: dehydroepiandrosterone (DHEA) and metformin) for a year. The results showed that on average, it was found that their biological ages had been reversed of 2.5 years. Additionally, their immune systems showed signs of rejuvenation.

The trial was created in order to test whether growth hormone could be safely used to restore the thymus gland that serves as a crucial function for the immune system (white blood cells mature inside the thymus, where they turn into T cells that help fight infection). This gland begins to gradually shrink after puberty and evidence from previous animal trials have suggested that the growth hormone can indeed regenerate thymus. However, growth hormone can also produce diabetes. This is why the trial added two anti-diabetic drugs in the reversal aging cocktail.

Of course further studies must be conducted to fully confirm and build on these findings but a meaningful amelioration of human aging appears to be remarkably promising in the horizon.

As the saying goes, you’re only as young as you feel…and apparently from what drugs you take...from now on. But remember, regular exercise appears to boost cognitive health in old age while diet is also a protective factor, especially for diets delivering omega-3 fatty acids, polyphenols, vitamin D and the B vitamins. There’s also evidence that having a healthy social life in old age can protect against cognitive decline. And as stated by Dorothy Canfield Fisher — an educational reformer, social activist, and best-selling American author in the early decades of the twentieth century — “Those who love deeply never grow old; they may die of old age, but they die young”.

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@Marina T Alamanou

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Life Science Consultant

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