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Aging Genetics and Aging

As life progresses from a phase to another, aging comes as an inevitable landmark in the path. But would aging be taken as culmination of an active  productive life or would it be welcome as a period of healthy coping with the new challenges? To decide that one may wonder about the definition of aging. However, we still lack a particular definition of aging, although with extensive scrutiny over the changes of cellular, molecular and physiological processes one encounters as the life progresses, aging can be very broadly defined as a “time-dependent functional decline that affects most living organisms” ( Serrano et al, 2013) . It is earmarked by a progressive loss of physical integrity which leads one to impairing of functions and increases vulnerability to death. This process also makes one increasingly susceptible to debilitating diseases like cancers, diabetes, cardiac and neurodegenerative disorders.

The advances in medical science has been increasing the average lifespan of the populations around the world, but also posing challenges of maintaining a healthy population of seniors for all of us. Aging healthfully has become a major concern and related research is gaining momentum . The discovery that the rate of aging is  showing its promises to be controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution is making one optimistic of increasing the lifespan and keeping one more productive at advanced age.There are different indications of aging, but nine features can be set as hallmarks control over which may help us to retard the process.

Reasons of aging

Our life is coded in DNA

DNA is the building block of life, contained in our cells that stores the information about our characteristics. It is under a constant threat from various physical and chemical sources that aims at changing its codes. The organisms have a DNA repair mechanism too in place. This not only tries to restore the DNA to its original state but also helps in maintaining the length of telomere. Unwanted changes in the DNA structure is a major cause of premature aging syndromes.Several of these syndromes may get coded into the defective DNA and may pass onto next generations.

We know about adult and childhood progeria as classic example of inheritable premature aging but this is also to reckon that Down’s  syndrome, a common inheritable disorder also induces premature aging. The Genetic tests may help us to detect the traits in an individual and help us to manage the cases not only for the person but also for forthcoming generations. Introduction of screening and diagnostic level tests even for rare diseases may help us to tackle these problems better. This is a major focus of Team Genetics, PatientMD. Advances in gene therapy based personalized medicine is showing promise of a permanent cure which soon may become a reality.

Is longevity determined by our genes?

It has been observed that members of few families in a region live longer compared to families living in same socio-economic and geographical locations. Thus the hypothesis is formed that the long living ones must have the secret of long-life coded in their genes. This doesn’t only indicate their lesser susceptibility to diseases but seems like there is much hidden in the genes.

In the last decade, with a better understanding of human genes at individual levels, extensive studies have been initiated to contrast the genes of people in their nineties (nonagenarians) and hundreds (centenarians, including semi-supercentenarians of ages 105-109 years and supercentenarians, ages 110+) with the general population. Although this branch of studies has a long way to go , but it has already been concluded that a few of the common variations (called polymorphisms) associated with long life spans are found in the APOE, FOXO3, and CETP genes. But these are not found in all individuals with highly exceptional longevity. These genes are generally involved into basic maintenance and function of body’s cells.But, there remains a bunch of genes unidentified yet which also contribute to longevity. At this point we are close to predict if one has an exceptional longevity coded in the genes but we are slowly embarking on a journey to tinker with the genes to increase longevity for the ones who lack such a genetic support .

Reduction in cognitive capacity- an indication of aging

A reduction in cognitive capacities and several other primary functions is a common indication of aging and it may be induced due to several factors. Gauthier (2014) opined that the arteries in the body start to stiffen as human body ages (probably starting from the aorta and the effect progresses gradually to the remaining organs of the body). He believed this to leave impact on the cognitive abilities. Aging process proceeds commensurately with a progressive loss in capacity to withstand stress, worsening in both homeostatic imbalance (an inability of the body to restore a functional, stable internal environment) and also the rate of disease incidences increase. As our age advances , the bodily oxygen consumption reduces steadily by 5-10% for every 10 years of aging, and this is thought to be one of the major reasons for function loss.

Telomere length: the yard stick of aging

 A commonly used proxy for cellular aging is the length of telomeres, the DNA and protein caps that protect the ends of each chromosome during cell division. These shorten slightly every time the chromosome replicates, until eventually the cell can no longer divide, becoming senescent or undergoing “apoptosis” – the cellular equivalent of suicide. Having shorter telomeres in the cells is associated with the onset of many age-related diseases, including hypertension, cardiovascular disease, type 2 diabetes and dementia. 

Healthy Heart

Several cardiovascular diseases start aggravating and affects the heart as aging progresses.The heart walls start loosing elasticity, and arterial systems become more non-responsive to pressure changes. Thickening of heart valves also get more asynchronous to heart beats. Aging also induces several metabolic syndromes which may include impaired glucose regulation, increased pressure in the arterials, raised plasma triglycerides. These also affect the heart functions and make one more prone to cardiac disorders.

“A regulated lifestyle, controlled food habits, moderate exercise may all slowdown these damages, and thus may control our aging, but in several cases these might be genetically determined too”; says Dr. Christ Pavlatos, CEO of PatientMD.

Genetic predispositions may make us more prone to several metabolic disorders and cardiac deaths. In US alone , around 400,000 cases of sudden cardiac deaths occur annually and “stratification of genetic risks and selection of therapies to the level of personalized medicine is becoming a reality as we are now empowered with precision level Next generation sequencing based genetic tests to understand the predisposition of a person to these risks, which may include cardiovascular, neurologic or metabolic disorders” adds Dr. Pavlatos. These all therapeutics may pave ways to rectify disorders and delay aging.We all know, a healthy heart creates a healthy, confident mindset too.

Stress and aging

Chronic stress is also known to accelerate the shortening of telomeres. A study published by Rosenkranz et al (2016) found that long-term meditators had a reduced inflammatory and stress response to psychological and chemical stressors in the lab compared with a control group. This took a cue from an earlier eye opening report by Quinn et al which stated that telomere length in the immune cells of people had appreciably increased after they took part in an intensive meditation . Intensive meditation training, immune cell telomerase activity, and psychological mediators

Jacobs et al revealed that activity of an enzyme called telomerase which rebuilds telomeres, increases, after a similar retreat.

We might be thinking that the stress free, highly controlled healthy lifestyle of a monk may help him to control aging, which is very difficult to adopt for a normal person, an interesting study may help us to think its a wrong notion that norma

Scientists at the University of Zaragoza compared 20 people who had been practising Zen meditation for an hour or more a day for at least 10 years with 20 people who had never meditated, matched for age, sex and lifestyle factors such as diet, smoking, drinking and exercise. All of them were subjected to a battery of psychological tests and gave blood samples so that the length of telomeres in their immune cells could be measured. The meditators group were found to be having a longer and a lower percentage of short telomeres in individual cells than those in the comparison group.

A woman does not age, atleast as much as a man does

“Age of a lady stops at 25 and starts to increase after she is 45”, is a hilarious way to mock a social behavior , but reliable scientific records are there to prove that in every situation and society , the females have more survivability. In in the last decade of the 20th century, the U.S. median life expectancy was 73.4 years for males and 80.1 years for females, a difference of 6.7 years, whereas in France it was 7.8 years and in the U.K. nearly 5.3 years.The aged population above 80 comprises of much more women, than men in every population. Its not just the effect of a less-orderly lifestyle of smoking and drinking by men compared to lesser number of ladies in that category because the female chimpanzees, gorillas, orangutans, and gibbons too live longer than their male counterparts who probably never drank alcohol or smoked.

The newborn male babies from their conception to the entire life span are found to be more vulnerable to several diseases than female counterparts. When the genes of an X chromosome becomes faulty, a lady has another X chromosome to compensate it, while the males, having XY chromosomes, lack that feature.Women also excessive battery of hormones, for example estrogen, that promotes greater longevity. Estrogen also helps in elimination of bad cholesterol and prevention of cardiac diseases. On the contrary, testosterone of males induces one to a more violent and risk-taking behavior.

A female body is more accommodative to make additional food reserves for pregnancy and breast feeding, while the men become more affected by over-eating and they possess less efficient mechanisms of elimination of excess foods.

The second half of the menstrual cycle increases the heart-beat of the females, this is akin to moderate exercise and the “jogging-heart” hypothesis says that this helps to keep the risks of cardiovascular diseases at bay. The males with a larger body , do have more cells, so the relative chances of harmful mutations increases; bigger body burns more calories and so risks of wear and tear of tissues are higher and moreover the higher height of the males make them more prone to long-term damages. 

Being more inquisitive towards the genetic differences between sexes may throw more light into the basis of aging and morbidity of humans.

Role of antioxidants

Since decades much have been deliberated about harmful oxidations in our body and foods and therapies that may eliminate these chemicals to retard aging. The female hormone estrogen also acts as a powerful antioxidant helping women to age more slowly.But these days we are too much lured to get as much as antioxidants as possible in form of medicines, food supplements to cosmetics that claim to reverse aging. Due to lack of scope I do not wish to elaborate on the facts and myths about these, but a report published by American Medical Association in 2007 is worth mentioning here. From an extensive series of 68 clinical trials , the experts of AMA opined that, antioxidant supplements do not reduce the risk of death.

Undo the aging

When all these processes of aging are coded in our genes and their products, recent technological and medical break-throughs have shows the hope that aging process may be viewed as a process that could be reversed, controlled or delayed little bit by working with genetic pathways and biochemical processes occurring in our body. To get a very safe and effective result, still we need to wait for several years for scientific exploration in tweaking with conserved laws of human body as set by nature.

Several lifestyle factors have been found to accelerate telomere shortening, such as poor diet, lack of sleep, smoking, drinking and a sedentary lifestyle.

An interesting article published by Dr. Ornish et al  in Lancet  showed that even a three month regime of comprehensive lifestyle change could appreciably increase telomerase activity in immune-system cells. Ten people under this study, who were diagnosed of low-risk prostrate cancer, were put under active surveillance, during a recommended alteration of diet, activity, stress management, and social support. The data were compared with 25 men who wee under same category but were not induced any such changes. There was a significant increase in telomere length proving that , yes we can reverse aging just by migrating to a healthier lifestyle.

Aging and our  society

As the average age of people is increasing over the years, specially in developed countries , it is also creating a pressure on the economy in terms of slowing down of GDP growth, rise in support costs and pressure in government budget as expressed in a 2017 report of IMF.

But several nations are taking up measures to change their perspective to see the aged population as a healthy happily living segment rather than a burden. This must be involving measures the middle aged populations to empower more with self sufficiency and prepare for a  happy retired life.There should be policy amendments, engaging local practice and awareness and guidance to individual people.One such commendable effort is from Public Health England, which launched a major new health marketing campaign – ‘One You’ – which aims to support people in their middle age to make simple changes that will help them to better prepare for later life.

The preparation for living healthy in retired life should start at midlife as healthy practices in midlife can lead to better health during the phase of decline.

Healthy aging is not just biological, its the mental age that matters too

Healthy aging is not only limited to biological and medical aspects of growing older, it encompasses a holistic aspect which covers body, soul and mind in the area of subjective experiences and interpretations, practicable imaginations that allows human autonomy, participations and good health . Advances in medical science will enable us to age healthily, but will that be a period of happy living? The answer lies within us. We must prepare ourselves to find the corners of happiness, satisfaction and interests to live in that extended happily-ever-after life.