The science of Ageing – Does Ageing need to be considered a disease?

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Jeanne Calment, a Frenchwoman born in 1875, was physically active and mentally sound till she passed away when she was 123 years. She outlived her daughter and her grandson and has been recognized as the world’s longest-living human. She cycled regularly until she sustained a leg fracture at age 100; smoked a daily cigarette until 117; and enjoyed “considerable” quantities of chocolate until her death. What made her live longer? Scientists are still debating if it was her genes or her gut biome or something else while you read on…

Encyclopaedia Britannica defines disease as a harmful deviation from the normal structural or functional state of an organism.

Well, to grow old is a blessing, the grey hair is after all a glorious crown. But to be honest, most of us usher into the ripe age with nary a hair on our crowns, nor a speck of calcium in our bones, the paths to our hearts cobblestoned with cholesterol, and our synapses fractured by the tau proteins. No wonder mankind has chased that elusive fountain of youth, regardless of the cost to self and the ecosystem. In fact, Charles Édouard Brownséquard, (of the Brown Sequard Syndrome fame of course), famously claimed that the injection of extracts from crushed dog testicles would allow old men to regain their potency – talk about a world that has gone to the dogs, literally and figuratively.

The last enemy to be destroyed is death, they said. The wise (wo)men of yore considered ageing as a natural extension of youth. In fact, life is a disease with death as its only cure, and humans should accept this truth and move on. But recent advances and the blooming cosmetic industry strive to prove otherwise. The result is a market flooded with yogurt cures, enema regimens, cell injections, magnetic devices, skin creams, herbal elixirs, glandular extracts, hormonal therapies, vitamin supplements, fad diets and torturous exercise programs, all to make sure the outside looks polished and branded, often with a little thought spared for what our insides crave. The obsession with the youth is so extreme, that people put leeches on their faces, inject paralyzing toxins into the skin, risk cancers, and inject hormones to ‘rejuvenate’ some hitherto unknown cells in the immune system, all in an effort to evade the inevitable. An emerging field with a fancy name – ‘Biogerontology’ is where researchers not only study the complex causes that trigger cellular ageing, but also devise ways to slow down, arrest, and reverse degenerative processes in living organisms.

So let us for a moment assume that physical aging is a curable disease. Then, what determines the ageing process? Is it in your genes to age gracefully or just the grace of God? Does stress eat up your vitality and hasten your end? Or it is what you eat that stresses your vital cell cycles? Will frequent sexual intercourse make you live longer? (Sure, if STDs don’t kill you first) or is it a microscopic protein in your telomeres? Will fasting help you look younger? To speak the truth, after aligning so many resources, money and time to this odyssey, we do not really know. Aging is after all multifactorial and the question if ageing is a pathology, is a conundrum.

Here is our knowledge of the tip of the ginormous iceberg, that is cellular aging.

Genetic programming: Genes program aging, but they do so only very loosely. Hence, even monozygotic human twins age differently based on their environment and lifestyle choices.  As the scientists dug deeper, they discovered the phenomenon called ‘replicative senescence’. The normal, differentiated cells have a fixed division potential before a ‘switch’ inside flips and the biochemical cycles in the cells just stop. The number of times they can replicate is predestined by a mastermind – the telomerase enzyme. Interestingly, when the cell is able to override this telomerase switch and becomes immortal, it becomes cancerous.

Fasting: Another widely studied fact is the effect of dietary restriction (DR)—underfeeding without malnutrition—in extending life span. At least in the labs, the effects of fasting on the body cells are phenomenal, resulting in as much as a 50% increase in rodent longevity. This could be why almost every religion in the world practices fasting at definite times of the year, be it Shravan, Ramadan or Lent (and why the people of yore were indeed wise).  Fasting is believed to reduce free radical formation- a byproduct of food metabolism which eventually triggers cellular aging. The radicles oxidize and damage the cell wall proteins and lipids, thus reducing the organ’s efficiency over time.

DNA Repair theory: The capacity for DNA repair is an important determinant of the rate of aging at the molecular levels. For e.g., the enzyme poly (ADP-ribose) polymerase-1 (PARP-1) is a key player in the cellular response to stress-induced DNA damage. In labs, the higher PARP-1 activity levels are associated with longer life spans in animal studies. What exactly regulates the upregulation and downregulation of PARP -1 is not yet clear. However, antioxidants play an important role in DNA repair and protection. Vitamins A, E, C, and B along with trace metals like copper, zinc, selenium help with cellular wear and tear repair. Cigarette smoke, saturated fats, and constant high blood sugars on the other hand damage the cell membranes and the DNA in long run.

Gut Health: Throughout the human life span, our gut microbiome, just like our fingerprints is unique. Those colonies of bacteria, virus, fungi are formed in your intestines shortly after you are born and its wonderfully quirky, that these biomes actually write your physiological fate. They determine your immunity, your allergy profile, your blood sugars, your cholesterol levels and even possess the potential manipulate the neurotransmitters in the brain. Over the lifespan, the gut microbiome follows some predictable patterns. The bacteria-virus-fungus profile change rapidly from infancy to age three, is stable up until middle age, and then shows an accelerated change starting in late adulthood. Studies have found that a lesser gut microbial diversity can lead to early development of frailty.

Yamanaka factors: The Yamanaka factors are a group of proteins that play a vital role in the creation of induced pluripotent stem cells. These factors control how DNA is copied for translation into other proteins. Thus, the upregulation of these proteins may be the ‘ambrosia’ the cells need to be alive and healthy. In December 2016, the Izpisua Belmonte lab published a landmark study in Cell journal. The researchers exposed the cells from certain organs to Yamanaka factors for short periods of time. These cells were stable (non-cancerous), in spite of the reversal of the age-associated hallmarks. Especially in the mice with a specific progeria syndrome, the reprogrammed mice looked younger; with better cardiovascular function, muscle mass, and improved regenerative capacity of the pancreas. Most surprisingly, the mice lived 30 percent longer yet did not develop cancer.

Most researchers opine that many of these theories work together to influence how we age. Now, coming to the age-old question of how not to age! Well, aging is as definite as the passing of time, and we all know, that time is a great healer but a terrible beautician. But there are certain ways to prolong the youth and live a fulfilled and healthy life: Eat Pray Love

1) Eat: They were not joking when they said you are what you eat. So eat mindfully and only when you are hungry. Binge eating is the pathological equivalent of whipping a fatigued horse (the weary horse being your cellular repair system stressed by your lifestyle and the pollution). Eat at fixed times, eat slowly and without a screen nearby. Make sure your diet has enough complex carbs to nourish the good gut bacteria in your gut, enough proteins to retain the muscle mass and enough good fats to keep your nerves and brain matter satisfied. I could go on and on about how you must quit smoking, quit alcohol, abandon sugar and butter, eat fresh fruits to up your antioxidant game, and drink green tea, but then, you can live to be a hundred if you give up all things that make you want to live to be a hundred. So, just do your best and pray for the rest.

2) Pray: By praying I mean do something that heals your soul and reduces your stress levels. You may meditate, sing, paint, putter, try journaling, write, dance or simply pray in silence.

3) Love: Love your Body. If for nothing else, love it for the marvel it is and how it puts up with your crazy schedules and survives years of abuse, which is a rite of passage for every medico. Do your muscles a favour and exercise atleast 30 minutes a day. Practice good posture and get some quality sleep. Spend time with your loved ones and pets. A persistent reduction in your cortisol levels is a surest way to stay young and charming. And yes making love helps too! According to multiple recent studies, frequent orgasms, at least 100 per year, can increase the life expectancy by around 3 to 8 years. Frequent touching is one way we enhance each other’s self-esteem and nothing will help you live longer than a strong and vital sense of self-worth.

Normal ageing is a complex process, that is progressive in nature and eventually causes the body to stop functioning, even in absence of disease. Pathological or hastened aging however is a co-morbidity that is a price we pay for modern lives. Addictions, poor lifestyle choices, diseases like diabetes mellitus, autoimmune disorders, cancers as well as cancer treatments can hasten ageing. This pathological ageing comes with a higher risk of metabolic diseases and cancers. The key to rein in any ageing process, however, is practicing a good lifestyle and accepting that one cannot live forever. Ageing is after all a dominatrix, who is herself light on her feet, but robs away your agility. She grazes your cells and she flirts with your homeostasis, till your organs swell, sigh, shrink, erode, in no particular order till they beg for mercy.

But philosophically speaking, if something comes to life in others because of you, then you have made an approach to immortality.

References:

Stefánsson H. The science of ageing and anti-ageing. EMBO Rep. 2005 Jul;6(Suppl 1):S1–3. doi: 10.1038/sj.embor.7400430. PMCID: PMC1369276.

https://inside.salk.edu/spring-2019/the-science-of-aging/

https://www.worldlifeexpectancy.com/sex-brain

Wilmanski, Tomasz et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humansNature metabolism. vol. 3,2 (2021): 274-286.

If something comes to life in others because of you, then you have made an approach to immortality Norman cousins.

 

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About the author

Dr. Pallavi Sawant-Uttekar is a Jill of all trades. She did her MD Physiology in KEM Hospital, Mumbai, followed by a Diploma in Diabetes. After practicing in Mumbai for about 5 years and then dabbling in medical writing for 2 years with WebMD she shifted to Germany, learnt German and is currently pursuing a house post in Gerontopsychiatry in Baden Wuerttemberg, with plans to do her Masters in Geriatrics. She is a passionate writer and an occasional poet. She has to her credit, multiple journal publications as well as short stories published in various anthologies.

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