Aging: Can it be retarded or even halted?

Physiology of Aging

Dr.Vivek Nalgirkar

3/10/2022 11 min read

o Let me first say, at the outset, why did I choose this topic. I travel all over India; I happen to meet students preparing for entrance exams. I do meet parents sometimes. Across the spectrum of age-groups, the one query that I always face is – “You don’t look your age; how have you retarded your age??!!!; any special tips…?”

I don’t take it as a complement though, because the profession that I am in prefers experience and wisdom (that is supposed to come with age) over youth (supposed to be inexperienced).

Everyone, young or elderly, is curious to know how the youth can be extended and aging can be postponed or retarded. Youth represents energy. A young mind tends to believe (rather falsely) about the aging – ‘It may never happen to me’; though it is the fact of life that everyone has to get old as the age advances.

o “I am 20-years old” is the common expression of one’s age. Even though 20-something is not biologically or conventionally an old age, it is a custom to call it that way; it recognizes the fact that aging starts from birth itself (or from the time of conception itself).

o “I am young at heart”, “I am 60-years young” are the expressions that we hear routinely, from someone who is attaining old age, or entering into that age group.

Age-landmarks from health perspective:

• “Up to 20 years, you can take your health for granted. Between 20 and 40 years, one should take little care of the health. Beyond 40 years of age, one should be absolutely vigilant about one’s health.”

Physiology of aging (senescence):

Process of aging starts at conception of life itself; it continues throughout life. It is an inevitable process.

At any given point of time, our age is reflective of: (a) the genetic constitution (the genetic make up of the individual), and (b) environmental influences. In other words,

AGING PROCESS AND ITS MANIFESTATION ON OUR BODIES IS REFLECTIVE OF TWO THINGS: (1) The genetic make-up: Our genetic constitution determines how our body fights off the environmental insults (inflammation etc); our bodies reflect our genetic capacity to adapt and repair. and (2) Environmental influences: The inflammatory conditions, oxidant stress, tissue injuries, etc.

It may be noted that INDIVIDUALS OF THE SAME CHRONOLOGICAL AGE VARY IN THE DEGREE OF SENESCENCE-RELATED FUNCTIONAL IMPAIRMENT AND THEREFORE DIFFER IN “PHYSIOLOGICAL AGE”.

Theories of aging:

Most of the theories answer or address only one of these two questions: “why do we age?” and “how do we age?”.

No one theory can completely explain the concept of aging. Many theories even contradict each other at a conceptual level. many theories with their overlapping hypotheses can make us understand the multitude of underlying processes.

(1)Biological aging:

-Initial flawed research demonstrated that, in an optimal environment, cells of higher organisms (chickens) were able to divide continually, leading people to believe our cells to potentially possess immortal properties. In 1960s, Leonard Hayflick disproved this theory by identifying a maximal number of divisions a human cell could undergo in culture (known as “Hayflick limit”).

-Modern biological theories of aging in humans fall into two main categories: (a) programmed theories, and (b) damage or error theories.

-The ‘programmed’ theories imply that aging follows a biological timetable (regulated by changes in gene expression that affect the systems responsible for maintenance, repair, and defense responses);

-Damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging.

(A)The programmed theory:

Programmed longevity – aging is the result of a sequential switching on and off of certain genes, with senescence being defined as the time when age-associated deficits are manifested.

Endocrine theory – Biological clocks act through hormones to control the pace of aging

Immunological theory – Decline in immune system; vulnerability to infections

(B)The damage or error theory:

o Wear and tear theory: Vital parts in our cells and tissues wear out resulting in aging

o Rate of living theory: The greater an organism’s rate of basal metabolism and basal oxygen consumption, the shorter its life span. RATE OF ENERGY EXPENDITURE WOULD DETERMINE THE LENGTH OF LIFE.

o Cross linking theory: (Glycosylation theory of aging): It is the binding of glucose to protein (a process that occurs in the presence of oxygen) that causes various problems. Once this binding has occurred, the protein becomes impaired and is unable to perform as efficiently. Accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes and thus result in aging. Examples – senile cataract, appearance of tough, leathery and yellow skin.

o Free radicals theory: The term free radical describes any molecule that has a free electron, and this property makes it react with healthy molecules in a destructive way. Because the free radical molecule has an extra electron it creates an extra negative charge. This unbalanced energy makes the free radical bind itself to another balanced molecule as it tries to steal electrons. In so doing, the balanced molecule becomes unbalanced and thus (becomes) a free radical itself. Superoxide and other free radicals cause damage to the macromolecular components of the cell, giving rise to accumulated damage, causing cells (and eventually organs) to stop functioning. It is now known that diet, lifestyle, drugs (tobacco, alcohol) and radiation etc, are all accelerators of free radical production within the body.

The oxygen toxicity, sometimes referred to as the “oxygen paradox”, is inherent in the atomic structure of oxygen.

Molecular oxygen (needed for life), upon single electron additions, sequentially generates the partially reduced molecules – superoxide anion, hydroxyl ions, and hydrogen peroxide (H2O2), which by further reactions can generate an array of additional reactive oxygen metabolites (ROMs). These ROMs cause extensive damage to biological macromolecules. The damage manifests as the peroxidation of membrane PUFA chains, modification of DNA, and carbonylation and loss of sulfhydrils in proteins.

There are some theories that dwell upon the psychosocial aspects of human behaviors': (1) Disengagement theory: The person’s connect with the society may be severed (for a variety of reasons); affecting the quality of life and hence hastens the process of aging; (2) Activity theory: This also describes the psychosocial aging process. It emphasizes the importance of ongoing social activity.

Some theories have been researched extensively and have widespread acceptance:

The neuroendocrine theory: This theory focuses on the role of hypothalamus in aging. As we grow older, the hypothalamus loses its precision regulatory ability and the receptors which uptake individual hormones become less sensitive to them.

The membrane theory of aging: There are age-related changes in the membrane’s ability to transfer chemicals, heat, and electrical processes that impair its function. AS WE GROW OLDER, THE CELL MEMBRANE BECOMES LESS LIPID (less liquid, more solid); this impedes its efficiency to conduct normal function and in particular there is a toxic accumulation.

The mitochondrial decline theory: Decline in the number, surface area, functional capacity of mitochondria; reduces the aerobic/oxidative capacity. Enhancement and protection of mitochondria is an essential part of preventing and slowing aging. Enhancement can be achieved with certain nutrients such as acetyl-L-Carnitine, CoQ10 (idebenone), NADH and some B vitamins etc.

Thus, aging experience and the effects of aging will vary from individual to individual. Some generalized observations though can be made regarding aging of each of the organ systems.

(1)Musculoskeletal system:

-Muscle mass is important on two counts – (a) The strength that it generates, and (b) the heat that is generated by muscle. Of the body’s resting metabolic heat generation, maximum is generated by muscle.

-The heat generated by muscle is a very a critical aspect of our cellular functioning. TEMPERATURE REGULATING SYSTEM IS ONE OF THE MOST EFFICIENT SYSTEMS IN THE BODY (very high “gain”). The reason probably lies in the fact that most chemical reactions at the cellular level need a stable steady temperature. (Thus, at rest, as well as when exposed to cold, the muscle contraction generates heat, so as to maintain the cellular biochemical reactions.

o Aging: (biomechanical & cellular aging)

Size and strength of all muscle tissue decreases with age.

Muscle fibers continue to become smaller in diameter : DECREASE IN THE RESERVES OF ATP, GLYCOGEN, MYOGLOBIN, AND THE NUMBER OF MYOFIBRILS.

Hence, muscular activity becomes less efficient; and more importantly, heat generation declines with consequent suffering of biochemical reactions.

(2)Integumentary system: (hair, skin)

In the animals living in cold climates, hair takes part in temperature regulation. Piloerection (“goosebumps”) traps air; this layer of air around the body prevents heat loss.

Skin: (1) Temperature regulation, (2) retains fluid, (3) absorbs shock and UV radiation – vitamin D synthesis. (4) Sensory inputs arise from the cutaneous sensory endings.

o Aging:

Hair loss and graying of hair – conventionally considered to be manifestations of aging. Increasingly it is being observed that these manifestations have begun to appear at an earlier age. (People seem to be very touchy about their hair loss!) Though hair loss can not be contained to a great extent, it creates a great psychological boost if the hair is dyed.

Skin:

(i)Dermis decreases in thickness (by 20%); hence loses its vascularity, cellularity, and sensitivity.

(ii)Its ability to exchange temperature with the surrounding and hence maintenance of body temperature suffers. Sweat and sebaceous glands decrease in number.

(iii)Sensory neurons decrease.

o Subcutaneous fat layer is thinned along the extremities; fat depots grow mainly on the abdomen and thighs.

(3)Respiratory system:

Decreased alveolar surface area for gas exchange; thus oxygen delivery to the tissues is going to be reduced. Exercise capacity is thence decreased.

(4)Cardiovascular function:

Slowdown of ANS function alters the cardiovascular status to a certain extent; there would be some decrease in the VO2 max.

HRmax = (220 – age in years); thus there is decrease in the maximum attainable heart rate that can maintain cardiac output.

(5)Endocrine function and metabolism:

-There is a generalized decrease in the endocrine function. E.g., decrease in the function of adrenal gland with the process of aging – adrenal cortex & medulla function declines

-Slowdown of metabolic processes – again the heat production will be less, thus resulting in altered ability of temperature regulation. This generalized slowdown results from decline in enzyme function.

-Decrease in muscle mass, associated with its unresponsiveness to insulin, may result in hyperglycemia and DM.

(6)Neurosensory function:

-Loss of neurons in the CNS

-Loss of neuronal dendrites; there is a loss of synaptic transmission

-The sense of smell, taste, vision, and olfaction are all diminished over time.

In summary, the elderly individuals are at a risk for hypothermia, apart from other loss of functional capacities of various organ systems.

How is the aging process manifested generically?

Changes in vision; visual acuity, presbyopia

Alterations in skin texture

Reduction in appetite

Greying of hair, thinning of hair/hair loss

Decrease in aerobic capacity; breathlessness on exertion (after climbing 3 floors, the person should be able to say his/her name or a full sentence. If not, it can be taken as reduction in aerobic capacity.)

HANDS – The most visible and reasonably fair indicator of the aging process. A mere look at one’s hands (palm or dorsum) can indicate his/her biological age.

How to retard aging? Age gracefully?

(Look young, feel young, be young)

Just as there is natural process of aging, is there something like anti-geria?

-There is a chronological age; nothing can be done about it. It is the number of years you have lived. However, it is possible that one looks younger than one’s chronobiological age.

-There is physiological age. This, I believe, is a sum total of efficiencies of the organ systems. After all, functioning of all organ systems is interrelated.

-There is organ age. Individual organ aging depends mostly on wear and tear theory. The organ that undergoes frequent inflammations or injuries/assaults from various agents, is surely going to age faster than the physiological age of that person.

Now, let’s see what all things can be done to retard the process of aging.

A man has 5 dimensions to his persona : (1) Physical, (2) mental, (3) intellectual, (4) social, and (5) spiritual.

(1)Physical well-being: The tripod of physical well-being is – diet, physical activity, and healthy lifestyle.

Three regimens are known to extend the maximum life span (MLS) of animals: (i) lowered ambient temperature in poikilotherms (cold-blooded animals) and hibernating mammals and (ii) a decrease in physical activity in poikilotherms, both of which decrease the metabolic rate, and (iii) caloric restriction.

Hibernating mammals such as the turkish hamster also live longer under hibernation, indicating the life-lengthening effects of hypometabolic states in mammals as well.

(A)Diet:

Is there any dietary content or dietary pattern that may retard the process of aging?

In a study on mice, there was differential gene expression pattern that resulted in aging. The aging process was faster in those who had a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals.

Caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.

The mechanism by which dietary restriction retards aging is unknown. Suggested mechanisms are – delay of immunologic aging, decreased free radical generation followed by reduced losses of mitochondria with age, preservation of protein synthesis capacities in old age, neuroendocrine effects, etc.

Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.

Age-associated biochemical, physiological, and behavioral changes are retarded by caloric restriction model.

HOW DOES CALORIC RESTRICTION WORK? How does it delay aging?

-Decreases blood glucose and insulin concentrations, improved insulin sensitivity, and lowering of body temperature.

-It may increase the glucocorticoid secretion; however, it does not lead to neoglucogenesis. Thus, care should be taken that – the restriction should be just about enough to mobilize the fat depots but should not lead to protein breakdown. Also, it should not lead to malnutrition.

-Caloric restriction has been shown to decrease the T3 levels.

-It attenuates the oxidative stress.

Some important points for dietary changes:

(1)Calculate your daily caloric requirement and intake. First calculate your BMI; see if it is either obese or just above normal.

(2)Let your caloric intake be just less by about 100-150 calories, to begin with. Monitor your weight/BMI/fat content periodically.

(3)Take the foodstuffs with low cholesterol content (lower the LDL cholesterol content). Cholesterol is the “fluidity buffer” in our membranes. It decreases the fluidity of the membranes.

(4)Drink a glass of water before each meal.

(5)Don’t allow the complete sense of fullness to occur during diet. Just short of it, stop eating.

(6)Take condensed proteins. The proteins should be of high biological value.

(7)Increase the fiber content in the diet.

(8)Endorphins have been shown to have a age-retardation effect; known to increase youthfulness. There are two ways to increase the endogenous opioid peptides – certain dietary contents are known to increase the secretion of gut peptides similar to endogenous opioids. Particularly, the spices, condiments, etc. There is also increased synthesis and secretion of POMC from the intermediate lobe of pituitary. The contents of the Chinese food preparations have been shown to release gut peptides similar to endorphins.

(9)Have tryptophan-containing diet. I call it the tryptophan-serotonin axis of the archicortex. It slows down all our bodily processes.

(B)Physical activity and healthy lifestyle:

Exercise is known to increase the release of endorphins. However, in my opinion, 30-40 minutes of intense exercise may be less beneficial. Instead, there should be physical activity/movement/exertion whenever and wherever possible.

I would like to suggest a 'slo-mo’ theory. Perform physical activity through the day. However, it should NOT be intense. Perform any physical activity at a leisure pace.

It should achieve a perfect balance between ‘rate of living’ theory and the maintenance of the aerobic capacity and muscular strength. Perform all actions slowly. Even while speaking, or performing any act, take double the amount of time. Do not rush through your acts. Any act, even eating, speaking, and all other actions, should be consciously executed very slowly. IT WILL DECREASE THE RATE OF WEAR & TEAR, DECREASE THE HEAT GENERATION, AND WILL ALSO KEEP THE NEUROENDOCRINE CLOCK HEALTHY.

What should be the ideal time to get up?

Our circadian rhythm starts with 6 o’clock tide of steroids. I believe getting up very early in the morning, when there is still some darkness left, will achieve two things: reduce the steroid spike and make oneself closer to the natural (evolutionary) tendency of staying in the dark.

(2)Mental dimension for health retardation: (Emotional quotient or EQ is now considered a critical measure of the wellness of an individual.)

o Negative emotions are absolutely hazardous; keep away from all negative emotions. Anger, rage, jealousy, revenge are such negative emotions that accelerate aging, via their influence on the neuroendocrine axis.

o Take life easy.

o Mind is controlled by the limbic system; at its center is hypothalamus. Hypothalamus has the program for aging, as per neuroendocrine theory.

o One way of being happy and youthful is to be less aware and less conscious of one’s own being. Most of the reasons of our anger and unhappiness emerge from a bloated ego, self-consciousness (we take ourselves too seriously).

o Stress causes glucocorticoid release. Try not take stress for petty things.

Thus, reducing glucocorticoid secretion and increasing endorphins and serotonin secretion should be the mantra for age-retardation.

(3)Intellectual dimension: (Remember, there is loss of neurons with aging.)

It is my observation that the people of high intellect age slowly and gracefully.

It is very important to have a steady flow (input & output) of intellect. Extraordinary people, with a high intellect, do not talk about persons or events; they talk about principles.

It may be things as small as reading of daily newspaper. But keep some time to feed your intellect. Take it as a therapy for aging. Read, write (if possible), exchange ideas.

Find a person whose intellectual level matches yours.

Try to learn new languages, new skill sets.

(4)Social dimension:

-Man is a social animal. Societal connect keeps us happy and strong

-Give happiness, take happiness in return. be happy, en

(5)Spiritual dimension:

-Increases the inner strength; makes the person stronger in taking any kind of stress.

In summary, it is possible to decelerate the aging process, by making some conscious choices and bringing about small alterations in the lifestyle.

Remember, happiness will increase the longevity of life and keep a person youthful and energetic over a longer period of time or age.