Insight 12 -Ways to forestall aging of the skin

Individual controls aging, Skin aging, , , , ,

Introduction

Despite the growing number of individuals joining the ranks of senior citizens, our culture remains focused on its youth and hence, there exists the pressure to stay young as long as possible.  The desire to preserve a youthful appearance is encouraged by the development of an abundance of cosmetics, creams, lotions, injections, chemical processes and surgical procedures to prevent, minimize or remove wrinkles, sags and fine lines.  These treatments are effective but undoubtedly expensive.  At the top of the list is the surgical face lift that lasts years, then injections of fillers of collagen or matrix-derived compounds needed every 8 months or so, and Botox injections that relax skeletal muscles and last several months.

However, understanding the science of aging skin allows one to sidestep these costly treatments and to minimize wrinkles, sags and fine lines with the least expense possible.  The two least expensive effective products to use are:  broad spectrum sunscreens and the retinoids.  Since 70% of age changes are controlled by the individual (see Insight 1), use of these products allows individual control.

Additionally, in reducing wrinkles and sags, many more important benefits occur. These benefits are:

(1)  reduced risk of skin cancers

(2)  improved skin blood flow assuring health of the skin and

(3)  retention of resident immune cells as first line of defense against infections. 

This blog will elucidate the essential knowledge on aging skin so as to achieve these essential benefits.

Verified age changes in the skin

Extrinsic/Intrinsic Aging

There are two types of aging processes that affect the skin:  extrinsic and intrinsic.  The former results from chronic exposure to externally generated irritants such as ultraviolet radiation (UVR), extreme temperatures and pollutants.  Extrinsic aging, commonly called photoaging, harms the exposed (unclothed) skin of the face, neck, arms, and legs.  Extrinsic factors rapidly accelerate the aging process and establish irreversible changes.

In contrast, intrinsic aging, also called normal aging, occurs very slowly as a result of internal changes such as nutrient availability, inflammatory damage and oxidative events.  Intrinsic aging occurs in areas that are usually covered by clothing or are hidden (such as the chest and back, buttock, underarms and behind the ears).  External factors have little effect on protected areas.  

There are three distinct layers to the skin : epidermis (top), dermis (middle) and hypodermis (bottom).  Because each layer contains different cells and relevant support material, each layer ages differently.  Since the focus of this blog is to discuss how to minimize wrinkles, sags and fine lines, only extrinsic aging which is the main cause of wrinkles, sags and fine lines,  will be detailed.

Wrinkles, sags, fine lines

Facial wrinkles develop mainly through external damage from solar ultraviolet radiation (UVR).  UVR consists of 3 different wave components:  UVA, UVB and UVC.  UVC is of no consequence as it does not enter the atmosphere.  UVA and UVB penetrate the atmosphere and injure human skin.

Epidermis of the skin

UVB penetrates the epidermis, the top layer of the skin but no more.  Too much UVB causes a sunburn.  Chronic UVB exposure irritates resident cells of the epidermis, called epithelial cells, and eventually induces a unnatural thickening of this outer layer. 

Dermis of the skin

Unlike UVB, UVA is insidious since it does not produce overt effects such as sunburn.  UVA penetrates down to the second layer of the skin, the dermis and damages the fibroblasts, the cells tasked with housekeeping duties of the dermis.  Fibroblasts traumatized by UVA progress to a terminal stage loosely termed senescent cells or scientifically termed, the senescent-associated secretory phenotype (SASP). 

SASP cells become tragic residents of the dermis because they are dramatically and permanently altered to cause chronic damage to the dermis.  These converted cells are notoriously harmful because:

(1)  the SASP is unable to divide and hence cannot renew itself, an effective way to eliminate oxidized compounds,

(2)  SASP aberrant function replaces normal fibroblast function. Consequently, the SASP produces an abundance of unwanted inflammatory mediators and harmful enzymes .  These substances destroy the support platform of the dermis.   

(3)  despite the harmful effects of the SASP, this cell type persists.  It is immune to cellular mechanisms to destroy it.

Consequently, these changes allow for gravity to overcome the  deteriorating weakened structure of the dermis to produce wrinkles and sags.  UVA-induction of the SASP is central to wrinkles and sags. 

Hypodermis of the skin

The hypodermis is the fatty layer under the dermis.  It, too, is affected by external damage from UVA.  Combined with normal aging, the hypodermis decreases in thickness.  Additionally, the matrix supporting the fat cells deteriorates and fat cells lose functionality, size and adherence to the dermal layer.  Thus another layer of support is modified in favor of wrinkles and sags.

Therefore, UVR-induced changes in the epidermis, dermis and hypodermis reduce the mechanical strength of the facial skin and other exposed skin and allow the forces of gravity to exert their effects, creating wrinkles and sags.  This is mainly brought about with chronic exposure to UVA.

Prevention of wrinkles and sags

Broad Spectrum Sunscreens

Since UVR is the major instigator of facial wrinkles and sags, blocking UVR with a sunscreen is a reasonable solution.  However, it was not until 2012 that the FDA approved the addition of UVA-blocking compounds in sunscreens.  Prior to this date, sunscreen only contained UVB-blocking substances to prevent sunburns. 

UVB blockers were termed sun protection factors (SPFs) and sunscreens were labeled according to the blocking strength of the UVB compound.  SPF ranges in strength from 15 to 75 or more.  With the realization that UVA, not UVB, causes skin cancers and facial aging, approval was granted to add UVA-blocking compounds to sunscreens.  Hurrah!!  Sunscreens with these compounds and UVB-blockers are now called broad spectrum sunscreens with SPF.  If used correctly (according to the directions), broad spectrum sunscreens will block both UVA and UVB radiation.  Chronic use of the broad spectrum sunscreens from a young age onward will significantly reduce wrinkles and sags. 

Two issues of importance: 

Firstly,  the compounds blocking UVA are of two types, ones that are absorbed and ones that are not.  Avobenzene belongs to the former; zinc oxide belongs to the latter.  So far both are considered safe but controversy has arisen regarding the safety of the absorbable anti-UVA compounds. 

Secondly, the chronic use of sunscreens limits the production of vitamin D in the skin.  If sunscreens are used constantly, this source of  vitamin D is inhibited and additional sources of vitamin D, e.g.  foods fortified with vitamin D or from supplements, are required.

Retinoids

Since protection against UVA was not available until 2012, most elderly today received generous amounts of UVA that caused facial wrinkles and sags.  To ameliorate this, the family of retinoids (retinol, retinaldehyde, retinoic acid also known as tretinoin), are beneficial.  Retinoids are essentially different forms of vitamin A.  When applied to the skin, retinoids reduce the photoaging effects of UVA.  In a number of small clinical trials, topical application of these compounds reversed or minimized age-associated facial lines, and wrinkles. 

It is known that retinoids activate epidermal and dermal cells with the result of enhancement of cell renewal, increased blood flow and maintenance of the dermal structure. Hence, retinoids reverse the damaging effects of UVA. 

The single major adverse effect with use of  retinoids is skin irritation or rash.  The mechanism for this is unknown and under investigation.   

Conclusions

Chronic external damage (mainly UVA) to a large portion of the skin causes wrinkles, sags and fine lines.  These are changes with serious psychological effects.  Importantly, underlying this is reduced physiological function of the skin that gives rise to skin cancers, poor wound healing and decreased defense against bacterial infections.

Use of broad spectrum sunscreens and retinoids protects the skin against extrinsic age changes. This assures many excellent benefits ranging from reduction in wrinkles and sags to optimal wound healing and decreased risk of skin cancers.

Insight 11 -Okinawa, DASH and Portfolio Diets

Individual controls aging, , ,

Diet to extend the health span

Innumerable scientific studies show that adherence to the Mediterranean Diet reduces deaths due to cardiovascular disease and therefore, increases the lifespan (see Insight 10).  As discussed below, several other diets, Okinawa, DASH, and Portfolio, reduce risk factors for cardiovascular disease. 

1.  Okinawa Diet

Background

Okinawa is a Japanese island where life expectancy since the end of WWII has been the highest in the world.  Although Okinawan life expectancy today is no longer higher than the Japanese national average, nevertheless, life expectancy in Japan relative to other countries remains exceptionally high.  As proof, Japan’s life expectancy ranks second among 191 countries  (average of both genders, 85 years in 2020  (www.worldometers.info/demographics/life-expectancy/). By comparison, life expectancy in the USA ranks 46 among 191 countries.

Okinawa Dietary Components

The Okinawa diet is the main factor contributing to the longevity of Okinawans and the plethora of centenarians.  The Okinawa diet is a plant-based diet that is high in consumption of vegetables and thus low in calories. Although low in calories, the diet is nutritionally dense with an abundance of vitamins and compounds with antioxidative effects.  Interestingly, the preferred vegetable, the sweet potato, is one with a low glycemic index, meaning it is metabolized slowly thus avoiding high surges in blood sugar that predisposes one to pre-diabetes and subsequent Type 2 Diabetes.  The diet includes moderate consumption of proteins and a selection of mono/polyunsaturated fatty acids in place of saturated fats.  Diet details are summarized below.  

Okinawa Diet Benefits

Clearly, the traditional Okinawa Diet as practiced by residents of Okinawa effectively forestalls the onset of age-associated diseases and increases the lifespan.  As discussed earlier (Insight 8), lifelong caloric restriction in many animal models from round worm to monkey, not only dramatically extends the maximal lifespan but reduces inflammation,  improves insulin sensitivity, and delays onset of diseases.  The Okinawa Diet is low in calories so it may provide benefits simply through reduction in calories. 

Additionally, the Okinawa diet is low in protein and high in low glycemic carbohydrates.  When mice are maintained on a diet comparable to the Okinawa Diet, their life span increases significantly.   Human dietary studies are difficult to perform but generally low protein consumption is not associated with a decrease in mortality.  On the contrary, diets high in protein and low in carbohydrates (opposite to the Okinawa Diet) are associated with increased mortality.  More data are needed to understand the role of protein in aging. 

Freshly dug sweet potatoes

2.  DASH Diet

Background

The DASH diet was developed more than 20 years ago to reduced the prevalence of hypertension.  DASH is an acronym for Dietary Approach to Stop Hypertension.  The prevalence of hypertension increases with age.  The prevalence in adults is ~ 30%, in those 65-80 years ~58% and as high as ~74% in those over 80 years of age.  Furthermore, elevated blood pressure predisposes one to cardiovascular diseases such as atherosclerosis, stroke and heart failure.

DASH Dietary Components

Previous science indicates that certain foods could possibly lower blood pressure better than other foods.  This became the basis of the DASH diet. This diet recommends consumption of fruits and vegetables, whole grains, low-fat dairy products, beans, nuts and seeds and some fish and poultry.  Also consumption of saturated and trans fatty acids and cholesterol is reduced.  This diet is rich in nutrients such as potassium, magnesium, calcium, and fiber and lower in sodium compared to a Western Diet.

The Mayo Clinic has put together 3 days of meals that follow the DASH dietary plan.  Also included is the nutritional analysis of the foods for the 3 days.  It is worth checking out.  https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/dash-diet/art-20047110

DASH Benefits

Numerous clinical trials show that the DASH Diet lowers both systolic (high number) and diastolic (lower number) blood pressure with greater reduction of blood pressure in those with higher baseline values.  Reducing sodium in the DASH Diet below the recommended amount produced an even greater reduction in blood pressure.

3.  Portfolio Diet

Background

This diet was developed to lower cholesterol and to prevent/reduce the onset of coronary artery disease. It was designed with scientific information that suggested certain foods (such as plant proteins and sterols, viscous fibers, nuts)  in various ways were helpful in reducing cholesterol.  High blood levels of LDL (bad cholesterol) is a serious risk factor for cardiovascular disease.

Portfolio Diet Components

The Portfolio Diet is basically a vegetarian diet.  It is rich in vegetables such as broccoli, eggplant, tomatoes, onions, okra, high in whole grains including oats and barley, and vegetable-based margarine, almonds, and soy protein. Soy products replace animal products and the accompanying saturated fat.  It is also low in sodium,  sweets, and refined carbohydrates.

WebMD has published a plan for what the typical Portfolio Diet would look like in daily life.  This is worth reading.  https://www.webmd.com/cholesterol-management/features/portfolio-diet-lower-cholesterol

Portfolio Diet Benefits

A systematic and meta-analysis in 2018 of the Portfolio diet in clinical trials longer than 3 weeks showed many benefits.  Benefits were reduction in LDL cholesterol, decrease in systolic/diastolic blood pressure, reduction in inflammatory factors and decreased risk of coronary heart disease.

Conclusions:

Whether you follow the diets discussed here or the Mediterranean Diet discussed earlier (Insight 10), there is ample evidence that inherence to these diets will result in longer healthier life.  Of the four diets, the scientific support for the Mediterranean Diet is the most extensive, but quality data also exists for the other three.

It is clear that all 4 diets differ radically from the typical Western diet.  The Western Diet is high in calories, saturated fats, meat and meat products, processed foods and sugar-laden foods. Consumption of fruits, vegetables and fiber is low.  Furthermore, the Western Diet is associated with development of obesity and cardiovascular disease.

Insight-11-referencesDownload

Insight 10-Best Longevity diet = Mediterranean Diet

Diet, Individual controls aging,

Best diet for longevity

I previously discussed in Insight 8 that severe caloric restriction retards the onset of many diseases and increases longevity in animal models of aging (including the monkey).  I subsequently presented the status of the future caloric-mimetic drugs. These drugs are predicted to offer the same benefits (health and longevity) of caloric restriction minus the pain of caloric restriction (Insight 9).  However, in the interim until the advent of efficacious caloric-mimetic drugs, the question remains as to what is the best diet for longevity building.  The best answer to date is the Mediterranean diet.  It is the diet with the most convincing scientific support.  Most importantly, adherence to this diet is associated with a decrease in the incidence of cardiovascular disease, the major cause of death in our society.  As a result, disease reduction indirectly increases lifespan.  

Components of the Mediterranean Diet

The Mediterranean diet entails consumption of whole grains, legumes, fruits, vegetables, nuts, fish and olive oil, wine in moderation, and a low-moderate intake of meat, dairy products, processed foods and sweets (Vitale et al., 2018).  This ~2000 calorie/day diet derives more calories from plant based foods than from meat based foods and fat consumption is largely from mono- and polyunsaturated fats.  More details are presented in the adjacent table.  This table is the result of an extensive systemic review (59 studies) of the health effects of the Mediterranean diet (D’Alessandro et al., 2019).  The authors were able to assess the effect of each food group on disease prevention. From that, they developed the frequency and serving size of the components of this diet needed to achieve these health benefits.      

Summarized from D’Alessandro et al., 2019

Origin of the Mediterranean diet

A study called Seven Countries Study of Cardiovascular Diseases began in the late 1950s and continued for some 50 years.  This seminal study tracked over 12,000 middle-aged men in North America, Northern Europe, and Southern Europe. It correlated dietary patterns with the incidence and mortality rates for coronary heart disease (CHD) and overall mortality (Menotti  and Puddu, 2015).  The striking findings showed that the incidence of CHD, other cardiovascular diseases and overall mortality was lower in southern Europe (Mediterranean countries and Japan) than anywhere else.  This improved health and longevity significantly correlated with decreased saturated fat consumption (low levels of serum cholesterol) and increased calorie intake from plant foods relative to animal meats.  In other words, this became known as the Mediterranean diet.

Proven benefits of the Mediterranean diet

There are numerous observational studies and clinical trials on the effects of adherence to the Mediterranean diet to health outcomes.  To make sense of the wealth of data, meta-analysis combines results from the  most rigorous studies to yield what are considered substantiated and valid conclusions.  The most recent of these meta analysis (Sofi et al., 2008; Dinu et al., 2018) evaluated 13 observational studies and 16 randomized clinical trials with regard to 37 different health outcomes. The results show adherence to the Mediterranean diet yields lower mortality for:

  1. Cardiovascular disease, Coronary heart disease, Heart attack
  2. Neurodegenerative diseases
  3. Cancers
  4. Diabetes
  5. All causes

However, there are limitations to studies assessing dietary patterns since they rely on validation of dietary questionnaires.  Hence, the need for the meta analysis that shows with a high degree of confidence that adherence to the Mediterranean diet compared to a non Mediterranean diet e.g. western diet, consistently yields valuable health benefits. 

Future – how the Mediterranean diet works

Several studies have endeavored to probe the underlying mechanism(s) of the Mediterranean diet on health benefits.  As a result, it has been shown, albeit in small studies, that the adherence to the Mediterranean diet for 6 months to one year lowers blood pressure (Davis et al., 2017; Jennings et al., 2019), improves dynamic blood flow (Davis et al., 2017), decreases proinflammatory mediators (Dyer et al., 2017) and reduces arterial stiffness (Jennings et al., 2019).

Other diets e.g. Okinawa, DASH and Portfolio will be discussed in my next blog.

ReferencesDownload

Insight 9 – Replacement for caloric restriction

Diet, Individual controls aging, , , , ,

The caloric restriction mimetic – better than starvation

Caloric restriction (CR) is severe reduction in calorie intake.  It must be maintained for an extended period of time and be supplemented with essential nutrients.  It is often called “starvation without malnutrition”.  However, the reward of this difficult protocol is exceptional:  a longer and healthier lifespan (see Insight 8).  The obvious problem is that, unlike animals under investigative experimentation, humans cannot endure this degree of starvation for any significant length of time.  Thus the search for drugs that would produce the same benefits of CR without the pain of eating less.  These drugs are termed caloric restriction mimetics (CRMs).

The caloric restriction mimetic – 3 of interest:

1.  Sirtuin (SIRT)-activating compounds e.g. resveratrol

2.  Metformin

3.  Rapamycin

Sirtuin-activating compounds

Sirtuin-activating compounds stimulate specific genes (SIRTs) to produce proteins termed sirtuins.  Sirtuins (chemically defined as NAD histone deacylases), in turn, act to change cell metabolism for the better.  Sirtuins perform several significant functions.  Some of these are 1) reduction of inflammation through depression of the master gene (NF-κβ), 2) greater recycling of damaged proteins, and  3) improvement of insulin signaling.  Together these activities and many more contribute to a healthier life.

How are sirtuins related to CR?  In animal models of aging, CR activates the genes (SIRT family) that produce the sirtuins and consequently, the level  of sirtuins increases with CR.  Secondly, in genetic experiments which insert an extra SIRT gene into an experimental animal, the level of sirtuins increases and beneficial changes comparable to CR occur.  So chemicals that elevate the level of sirtuins should produce the same beneficial effects of CR.  Thus the development of sirtuin-activating compounds.

Resveratrol – role in caloric restriction

A notable sirtuin-activating compound is resveratrol, originally isolated  from red wine and when concentrated (1000 fold), resveratrol produces effects similar to CR such as an increase in maximal lifespan, reduced inflammation, and delay in disease onset.   Unfortunately, resveratrol is poorly absorbed by the gastrointestinal tract and so analogs with greater bioavailability have been developed.  Analogues have been evaluated in rodents and in man.  Generally in rodents, improved health benefits e.g. delay in disease onset have been observed. 

In man, clinical trials assessing one particular analogue, SRT2104, for therapy of psoriasis, ulcerative colitis, sepsis, and vascular dysfunction in smokers and type 2 diabetes (T2D) have been completed.  Thus far only results for the effect of oral SRT2104 on psoriasis have been published and showed reasonable safety and a modest reduction of disease pathology.  This was a small study (40 patients, 84 days of treatment) that warrants additional evaluation according to Kreuger et al., (2015).   As published results become available, updates will be provided.

Metformin

Metformin is a caloric restriction mimetic.  It is also an FDA approved drug for treatment of T2D. Much is known on how it works to block production of glucose by the liver.  A striking finding was that patients taking metformin for T2D lived longer than those without diabetes and of course not taking metformin.

When used in animals, metformin delays the onset of disease and in some animal models of aging, it extends the lifespan.   It acts in multiple ways to alter nutrient sensing and improve cellular activities related to gene function, recycling of damaged cell components and slowing age-related changes.  These changes mirror those produced by lifelong CR. 

To further understand the caloric restriction mimetic effects of metformin, the FDA (2016) granted approval of its use in a clinical trial to determine whether metformin will delay the onset of disease.  The trial named Targeting Aging with Metformin (TAME) trial will enroll 3000 patients (65-79 years of age) and follow them for 6 years to determine whether metformin delays the onset of major age-related diseases e.g. heart disease, cancer and dementia (https://www.afar.org/tame-trial).  The results are eagerly awaited.

Rapamycin

Rapamycin is an antibiotic and potent immunosuppressant drug to prevent organ rejection.  In animal models of aging including the mouse, treatment with rapamycin extends the lifespan and delays the onset of age-related diseases.  Thus rapamycin is a caloric restriction mimetic.  It acts by inhibiting an important nutrient sensor called mTOR.  This nutrient sensor is activated by insulin.  Therefore, in the presence of rapamycin,  insulin-mediated metabolic effects are significantly reduced. 

Chronic use of rapamycin in man is limited to very low doses due to untoward side effects. However, the Dog Aging Project completed a placebo-controlled trial with 24 healthy companion dogs treated with a low dose of rapamycin for 10 weeks.  The drug is safe and improves cardiac function as determined by an echocardiogram before and after treatment.  Funded by a grant from National Institute of Aging and private donors, the next experiment will enroll a larger number of companion dogs and seek to determine whether aging can be delayed in dogs with this CRM.  

The objective of the Dog Aging Project (dogagingproject.org) is to understand aging in dogs and translate the information to humans.  This is based on observations that humans and dogs share the same environment, they have many biological mechanisms in common and also develop many of the same diseases.  Insights into dog aging should contribute to understanding human aging.

Comparison of diet and mimetics

Common Pathway

The schematic illustrates one known pathway altered by CRMs.  As with CR, these drugs also target the nutrient sensor termed mTOR (mammalian target of rapamycin).  This sensor was uncovered in part with studies using rapamycin.  mTOR is a key protein that affects many other essential pathways in the cell.  When its activity is reduced, more efficient metabolism ensues, recycling is enhanced and inflammation is minimized. The future caloric restriction mimetic will potentially replace dietary caloric restriction.

References of interest

1.  Krueger JG, Suarez-Farinas M, Cueto I et al.  A randomized, placebo-controlled study of SRT2104, s SIRT1 activator in patients with moderate to severe psoriasis. PLoS ONE 10(11): e0142081

2.  Kulkarni AS, Gubbi S, Barzilai N.  Benefits of metformin in attenuating the hallmarks of aging.  Cell Metab 32:  15-30, 2020.

3.  Urfer SR, Kaeberlein TL, Mailheau S.  A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle aged companion dogs.  GeroScience 39:117–127, 2017.

Insight 8-Caloric Restriction

Diet, Individual controls aging, , , ,

Importance of caloric restriction (CR)

Previous blogs have focused on specific organ-systems such as skeletal muscle (Insights 2-5) and the brain (Insights 6,7).  Insight 8 describes a proven but difficult path to longevity that impacts ALL organ-systems. This path is one of rigorous caloric restriction. Thus caloric restriction promotes longevity. It is a longevity builder.

Low calorie foods

Not quite a century ago, a Cornell University researcher, Clive McKay who was studying nutrition in rats, reported that rats who ate 30% less calories than those with free access to food, appeared healthier and lived longer than the controls with unlimited access to food.  All rats consumed adequate intake of vitamins, minerals, essential amino acids and fats throughout the study.

Significance of caloric restriction

First, CR is a repeatable experiment. It has been replicated in many different animal models that include yeast, round worms, fruit flies, mice, dogs, and monkeys.  In all studies, CR restriction of 25-30 or more percent produces a significant extension of lifespan with positive effects on a variety of organ-systems.  

Secondly, the CR studies revealed at least one important mechanism of aging. Thus scientists now know that lifespan (at least from yeast to monkey) can be successfully lengthened with reduction in consumption of calories.

Thirdly, CR opened the door to the identification of drug “mimetics” of CR. These new drugs would work like CR but, importantly, bypass the known difficulty for humans to eat less.

Known benefits of caloric restriction

CR produces many benefits in addition to an increase in lifespan.  This has been studied in depth in rodents and monkeys.  Generally, compared to control animals, CR animals exhibit

   (a) a delay in the occurrence of major diseases,

   (b) a delay in the decline in muscle mass,

   (c) a delay in the decline of the immune system, and

   (d) a delay in the decline in some DNA repair mechanisms (protecting cells from random damage). 

Body temperature may decline slightly but overall physical activity in CR animals compared to controls is normal or slightly increased.  Significantly, and considered the driving force behind the above beneficial changes is a shift in how sugars are metabolized.  CR animals utilize new pathways that  reduce the requirement for insulin, a known pro-aging factor.

Results of CR in monkeys

One of the most important studies on CR are the ongoing ones using Rhesus monkeys at the National Institutes of Aging (NIA) and Wisconsin University (Colman et al., 2014; Mattison et al., 2017).  Monkeys began a 30 percent reduction in calories when they were adults.  After 20 years, the number of CR-treated monkeys exceeded that of the controls (survival in the CR group was 80% versus 50% in the control group).  Other benefits, to name a few, include:

   (a) a delay in age-related pathologies such as diabetes, cardiovascular disease, cancer and brain-related disorders;

   (b)  lower blood pressure, heart rate, fasting blood glucose and a favorable lipid profile (low LDL and triglycerides and high HDL);

   (c)  normal levels of testosterone and estrogen, maintenance of “youthful” levels of melatonin (sleep agent) and dihydroepiandrosterone (DHEA popular supplement considered the precursor to hormonal steroids such as estrogen and testosterone);

   (d) maintenance of immune system function (lower levels of inflammatory mediators and higher levels of anti-inflammatory agents); and

   (e) decreased oxidative damage to muscles and decreased onset of sarcopenia (see Insight 2). 

Application of caloric restriction to man

The first study in man was an observational, retrospective and case-controlled study of 18 volunteers (average age ~ 50 years) in self-imposed CR for 3-15 years paired with 18 healthy same age, sex, but eating a western diet (high fats and carbohydrates).  Compared to those eating the western diet, CR individuals had a lower body mass index, less body fat, more lean muscle mass, lower levels of LDL, triglycerides and fasting glucose and insulin and higher HDL and lower levels of a key inflammatory mediator, C-reactive protein (Fontana et al., 2004).

NIA sponsored the clinical trial, CALERIE = (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) Study  which has completed several small (~50 volunteers) phase I trials of 6 months to 1 year duration and a larger (218 volunteers) phase II trial that lasted 2 years.  In both phases the target caloric reduction was a minimum of 25% but in phase I, individuals achieved a 10-17% caloric reduction and in the longer trial, only a 12% caloric reduction was achieved.  Even with this modest CR, there were positive changes such as decrease in fasting glucose, decrease in inflammatory makers, improved cell function and decrease in cardiovascular risk factors.  However, the CR reduction was too modest and phase II too short to achieve the milestones evident in the monkey studies.

Caloric restriction – next steps

The difficulty for humans to adhere to a 30% reduction in calories has ushered in interest in developing drugs to “mimic” CR.  As the thinking goes, in the future, individuals will be able to take a drug that mimics CR and also be able to eat whatever is desired.  Three candidate drugs have been proposed:

a) metformin

b) rapamycin

c) sirtuins

A discussion of these 3 compound will be the topic of my next blog.

References                          

Fontana et al.,  Proc Natl Acad Sci USA 101:  6659-63, 2004.

Colman et al., Nat Commun 5:  3557, 2014

Mattison et al., Nat Commun. 8:  14063, 2017.

Insight 7 – Brain Health and Sleep

Brain aging, Individual controls aging, , ,

Brain toxins and their disposal by the brain

One of the most exciting discoveries in the past decade is the identification of a “disposal” system in the brain that clears the brain of unwanted compounds (toxins), produced in the course of everyday living.  This system is termed the glymphatic system.  It shares a large portion of its name with a similar system that resides outside the brain.   This outside system is the immune lymphatic system  that protects us from viral and bacterial infections.

Characteristics of the glymphatics; importance of sleep

Unlike the immune lymphatic system, the glymphatic system resides solely in the brain and functions to clear proteins or parts of proteins that accumulate as byproducts of normal brain metabolism.  The main function of the glymphatics is to clear toxins.  Toxins filtered by the glymphatics in the brain are transported in small vessels down the neck and literally dumped into the immune lymphatic system for recycling or elimination elsewhere.  Thus the glymphatics contribute significantly to brain health and longevity!

Importantly, the glymphatic system only works at night.  It is associated with high frequency brain waves and low levels of norepinephrine, an essential brain regulator, that only occur during sleep.  Results of animal studies show that natural sleep produces the essential changes that facilitate the clearance of toxins, in particular beta amyloid protein, implicated in the development and progression of Alzheimer’s Disease.  Therefore, sleep appears to serve an extremely important function – enhancing the clearance of metabolic waste products.  As summarized by researchers at the Langone Medical Center, New York University “restorative function of sleep may be due to the switching of the brain into a functional state that facilitates the clearance of degradation products of neural activity that accumulate during wakefulness” (Xie, Kang, Xu et al., 2013).

The clearance of toxins by the glymphatic system applies to all neurotoxins.  It is postulated that reduced clearance of neurotoxins may contribute not only to the development of Alzheimer’s Disease but may influence the presence of several other diseases e.g. Parkinson’s Disease, Huntingdon’s Disease, amyotrophic lateral sclerosis and frontotemporal dementia.

Age-associated changes in sleep may retard toxin clearance

Age-associated Sleep Stages

Unfortunately sleep quality decrease with age.  Sleep physiology consists of 4 stages per each sleep cycle and the occurrence of about 8-9 cycles per night.  Different brain activities occur in each stage.  For example, stages 1 and 2 constitute light sleep while stages 3 and 4 comprise deep sleep and are followed by REM (rapid-eye movement) associated with dreaming.  Additionally, there is a period of quiet wakefulness prior to sleep. 

With age, the following changes occur:

(1) the period of quiet wakefulness increases such that it takes longer to fall asleep

(2) the time spent in stages 1 and 2 increases – increasing the number of awakenings referred to as sleep fragmentation

(3) the time spent in deep sleep (stages 3 an 4) decreases and may disappear – resulting in the feeling of “not rested”

These changes may lead to daytime “napping” and possibly progress to insomnia.  Many factors such as medication use, nocturnal urinary frequency, chronic pain, hormonal changes and age-related co-morbidities, exacerbate age-related changes in sleep patterns. 

It is important to know how age-related changes in sleep affect the function of the glymphatics.  Regrettably, this has not been critically studied in the elderly.  It is known that the extreme condition of no sleep, insomnia, shuts down the glymphatics, allowing build-up of neurological toxins. 

How to improve quality of sleep

There is no firm answer on how to improve sleep quality.  Clinical trials, generally small with 40-60 participants, point to two interventions that improve sleep quality in the elderly:  a program of aerobic exercise and cognitive behavior therapy (CBT).  Insight 4 provides sufficient detail for a meaningful program of aerobic exercise.   

CBT is a program that provides instruction on the essentials of sleep. This program includes

1)  sleep compression (slowly reducing the amount of time spent in bed (not sleeping) to obtain the optimal sleep time)

2)  sleep hygiene principles focused on appropriate activities, diet, liquids prior to bed time, daytime physical and social activities, light exposure, sleep environment

3)  need to keep a sleep diary and make revisions as necessary 

The CBT program (above) was used in a 4-week program for elderly attending a Veteran’s Adult Day Health Care program.  The CBT was successful in enhancing sleep quality in elderly individuals compared to controls who received general information but not CBT.  This benefit persisted at follow-up 4 months later (Martin et al., 2017).

Reader comments on this discussion are encouraged.  Experiences that enhance sleep quality are of special interest. 

References

1.  Xie, Kang, Xu et al., Sleep Drives Metabolite Clearance from the Adult Brain Science. 18; 342(6156), 2013.

2.  Martin, Song, Hughes et al., A four-session sleep intervention program improves sleep for older adult  day health care participants:  results of a randomized controlled trial. Sleep 40: 1-12, 2017

3.  Reviews:

Jessen, Munk, Lundgaard, Nedergaard. The Glymphatic System – A Beginner’s Guide.

Neurochem Res. 40: 2583–2599, 2015.

Sun, Wang, Yang et al., Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases. Progress in Neurobiology 163–164 : 118–143, 2018.

Insight 6 – More longevity building: Ways to minimize brain aging

Brain aging, Individual controls aging, , , ,

Loss of memory with age is a widespread concern

any older adults have concluded that the only age change really worth caring about is that which slowly robs them of their ability to think.  Generally, muscle weakness, loss of balance and even loss of independence are often rated as less important than the loss of mental capacity that is defined as dementia.  It is important to know that dementia is not a normal age change but rather a neurodegenerative disease that at present has no cure or well defined cause.  Since aging is the main risk factor for disease and since the environment contributes significantly to the rate of aging , not intervening with known strategies will negatively impact memory as well as overall brain function.  Therefore, for longevity building, it becomes especially critical to know the latest and best information that will help preserve brain function.  This blog reviews the science on this topic and relates proven interventions. 

Numerous tests track aging of the brain

Thinking is complicated and so there exist many tests that measure each unique aspect of mental function.  For example, there are tests to measure verbal memory, visual memory, associative memory, source memory, perspective memory, processing speed, spatial navigation, and the most complex, executive function.  Interestingly and importantly, results of many studies that assessed these various brain functions over extended periods of time (more than 30 years in some studies) showed that some components of brain function have the potential to decline while others are quite stable throughout the lifespan.  Thus brain aging appears to be “selective”.   It then becomes important in longevity building to optimize those activities which have a tendency to deteriorate.

Brain functions that remain constant with age

Brain regions – where thinking occurs

Mental functions that do not change with age include semantic memory, most aspects of language, autobiographical memory, emotional processing, and automatic memory processes. Specifically, semantic memory is the memory of facts and knowledge learned over the lifespan.  This remains stable with age although the speed with which this knowledge is retrieved may be slowed.  Language refers to things such as use of appropriate grammar rules and pronunciation.  These are not forgotten and also remain constant.  Autobiographical memory is an individual’s personal history and it, too, is unwavering with time.  Emotional processing refers to typical emotional responses to problems or difficult situations.  Emotional processing takes many forms e.g. abrupt, calm, thoughtful, anxious etc.  Individual emotional processing modes do  not change with age and for the most part, one’s emotional processing at 90 years will mirror that at 30 years.  Finally, automatic memory processes remain stable over time.  Automatic memory relates to things done with minimal mental input or done by rote or constant repetition e.g. driving a car, riding a bike, making coffee, playing tennis.  They are activities that have become so routine that they seem to be accomplished without thinking.  Instability or loss of automatic memory processes usually signals the presence of neurodegenerative disease.

Brain functions that decline with age; longevity building with proven interventions

Mental functions that weaken with age include a) a slowing of information processing speed, b) a decline in executive function, and c) a decrease in specific memory functions that include encoding and retrieval processes, associative, source finding and prospective retention.  This breaks down into the following: information processing speed refers to the quickness at which one can process and respond to information.  This decrement is highly significant since it is a major reason for accidents, mistakes and even falls.  This means that the mental response to novel situations is slowed and depending on the situation, may result in an unfavorable outcome.  Fortunately, processing speed can be improved with practice (see below).  Executive function encompasses various memory skills and abilities to use information to solve daily problems.  Thus, the age-associated decrease in executive function will impinge on important activities such as shopping, banking/finances, house management, medication oversight and meal preparation.  The decline in specific aspects of memory are not as serious as the reduction of information processing speed and executive function but are frequent complaints of the older adult such as not remembering who told me that or where the information came from (source finding memory) or not remembering the reason for doing something, for example, opening the refrigerator door (encoding and retrieval memory) or working on a project and forgetting about a future task such as to turn the oven on at specific time (prospective retention memory).  Whereas these cognitive activities tend to deteriorate with age, proven interventions of intense learning experiences can significantly reduce their loss.

Longevity building – proven interventions to slow brain aging through brain remodeling

Results of numerous animal studies and now many studies in humans using sophisticated imaging techniques such as an MRI and other scans show that brain aging can be minimized and cognitive function of the older adult can be maximized by

a) a program of aerobic exercise (Insight 4)

b) continued engagement in serious mental stimulation

c) mastery of new skills

d) making sure vision and hearing is the best possible. 

These lifestyle choices improve/maintain the connections between brain cells (neurons) and assure their survival.  The effect on the brain is referred to as brain remodeling or positive neuroplasticity. Thus these specific interventions physically alter or remodel the brain in a favorable way.

1) Longevity building with aerobic exercise

Aerobic exercise yields many benefits.  With regard to cognitive function, aerobic exercise improves blood flow to and throughout the brain, promotes formation of new blood vessels, and  improves brain metabolism, thereby reducing accumulations of neurotoxins, substances that harm or kill nerve cells.  Recently, results of animal studies, now supported by data obtained in man not only in young but also older individuals, show increased formation of nerve cells as well as more nerve connections in specific brain regions (brain remodeling).  This supports earlier studies that show a correlation with fitness and cognitive function such that the higher the fitness level, the better the score on various cognitive tests (mentioned above) and the better the brain activity as recorded by a functional MRI scan (a scan that can localize which part of the brain is doing the thinking).

2) Longevity building with participation in intellectually complex work

There is considerable debate as to whether retirement harms brain function.  Initial findings reported a significant decline in brain activity following retirement.  This implied that loss of work-related brain stimulation was a major factor in brain aging and that the continuation of intellectually complex work after retirement served to prevent this loss.  Continuation with complex intellectual activities remains important but current data point to a high degree of variability regarding brain stability after retirement.  The best studies indicate that decline in brain function is evident following retirement but the onset and rate of this decline is highly variable and depends on many factors, for example, complexity of job, health at retirement, satisfaction with the job, educational level.  What is not disputed is that:  part time work post retirement preserves cognition for a significant period of time, hence continuation of complex intellectual activities remains of importance.  Additionally, several small clinical studies show that engagement in solving of complex abstract problems reduces brain aging.

3) Longevity building with learning a new skill

Skill training is specific training for a specific task.  It includes, for example, learning a new language, learning to play a musical instrument, learning computer skills, learning to crochet, and learning to ski.   Learning a new skill, although relatively easy for an adolescent and young adult,  has generally been considered more challenging for the older adult.  However, skill learning prevents decline in brain function.  This is confirmed by studies using brain scans that show positive brain remodeling in the older adult equal to that of the young adult.  Furthermore, it is now known  that for a) skill mastery and b) long term retention, the older adult benefits from training sessions that are seriously challenging and complicated.  This approach favors the best outcome for the older adult. 

Two important clinical trials (ACTIVE, IMPACT) evaluated the effect of proprietary computer programs to improve memory, reasoning and processing speed with specific practice exercises over a 10 week period.  Both studies yielded positive results such that practice test scores in memory, reasoning and processing speed increased with these programs.   The extent to which these improvements are maintained over time has not been studied as yet but would be important to know.

4)  Longevity building with sensory enhancement

There are a number of age changes that diminish the sight and hearing of the older adult.  In the absence of disease these age changes are correctable but unfortunately, they are frequently ignored.  As a result, eye sight and hearing are compromised.  The denial of hearing loss is especially common.  What is not appreciated is that failure to correct these sensory deficiencies is a big factor promoting cognitive decline.  This is because  these deficits reduce the quality of information that is received.  Referred to as “noisy processing” the brain receives inaccurate or fuzzy information which does nothing to promote learning and intellectual stimulation.  Over the long term, little knowledge is gained, and little thinking is done, with the outcome of accelerating brain aging.  Corrective lenses and hearing aids will add measurably to optimizing brain function.

5)  Adequate sleep

Adequate sleep is an important factor in preserving cognition.  This will be the topic of my next blog which points out the relation between adequate sleep and the newly discovered filtration system in the brain that removes neurotoxins.  This is a potential link between sleep, cognitive decline and neurodegenerative diseases.

Insight 5 – Optimizing Balance

Exercise, Individual controls aging, , , , ,

Benefits of a stable balance

Good Balance

Good balance is absolutely essential to prevent falls.  Reliable balance also assures an optimal comfortable walking pace.  Results of clinical trials tells us that strength and balance exercises will definitely help us avoid falls and get us safely from point A to point B.  In other words, you can minimize your risk of falling and improve your walking pace through a proven exercise program (given below).  On the other hand, ignoring these exercises will guarantee a high risk of falling and bring on an abundance of unwanted consequences.

Balance depends on biology that changes with age

Balance deteriorates with age.  There are many reasons for this.  Firstly, declining sight and hearing contribute to poor balance.  Secondly, years of poor posture exacerbated by weak back muscles and loss of bone mass produce a compressed spine or a “hunched” back that reduces upright stability.  Thirdly, the sense of touch and the sense of muscle/joint position decline and hence need to be retrained.  Reduced sight and hearing may be readily improved with correctives lenses and hearing devices but sadly these are often ignored.  Other decrements are best minimized through resistance and balance exercises.  Age-associated decline in balance is modifiable; modifications will definitely build longevity by lengthening the health span.

The cost of a fall is high

Approximately thirty percent of elderly fall at least once a year.  Avoiding a fall is of paramount importance because the consequences of a fall are all negative.  The least negative might be a sore muscle but more commonly, it is a broken bone e.g. hip.  Broken bones require hospitalization, medical expenses, and significant recovery time that limit independence.  Hip fractures are especially harmful since they are associated with an elevated risk of dying, a risk which persists for years after the fracture.  Another outcome after a fall is onset of an unavoidable psychological mentality called “fear of falling”.  This plays a role in producing a slower, more cautious gait that unfortunately is incredibly damaging in the long run. 

The cost of slowed gait is high

Poor balance leads to an unsteady, hesitant walking gait.  This compromises posture and reduces further the existing poor balance.  This downward cycle favors a fall.  Slowed gait also limits mobility and independence.  Performance of daily tasks take more time and therefore, become more difficult.

Balance exercises are part of the 4-Prong Exercise Program

Previous blogs discussed progressive resistance exercises, aerobic exercises, and stretch exercises.  Additionally they discussed the validity of these exercises to modify various age changes, to increase the health span and to build longevity.  The final essential exercise to add to the preceding 3 is balance.   Balance exercises are critically important for retraining the sensory perception pathways in the joints and muscles of the feet, ankles, legs.  Balance exercises need to partner with specific resistance exercises to be totally effective in optimizing balance and preventing falls. 

Evidence to show balance exercises works

Results of several clinical trials provide evidence that specific balance exercises coupled with moderate intensity lower limb resistance exercises improve balance stability and reduce the risk of falling.  These trials (both sexes, community dwellers, 65 years and older, one study with women with osteoporosis) employed several standardized tests to measure balance before and after the interventions (resistance and balance exercises for 6-12 months) and traced the incidence of falls in the control and exercising groups.   

Exercises to improve balance; balance type

Here are the balance exercises used in the clinical trials mentioned above.  Balance exercises are initially practiced for 10 seconds and increased over time.  The more practice, the better the improvement in balance.

(1) standing with one foot directly in front of the other;

(2) walking placing one foot directly in front of the other;

(3) walking on heels;

(4) walking backwards, sideways and turning around;

(5) stepping over objects;

(6) bending and picking up an object;

(7) stair climbing in the home;

(8) rising from a sitting position to a standing one;

(9) knee squat.

Exercises to improve balance; resistance type

Here are the resistance exercises used in the clinical trials noted above and shown to be successful in improving balance in the elderly and decreasing risk of falling.  They are the (1) hip extensor, (2) hip abductor, (3)  knee extensor, (4) knee flexor, (5) inner quadriceps, (6) ankle plantar and (7) dorsiflexor muscle exercises.  These exercises are fairly simple to do and are described below.  They should be initiated without ankle weights and one set of 10 repetitions.  When ready, add an ankle weight of 1 pound and progress up to 6 pounds; increase the number of sets.   The greater the weight and the number of sets, the better the improvement in balance. The combination of  balance and resistance exercises are performed a minimum of 3 times a week for approximately 30 minutes.

Specific resistance exercises proven to improve balance

1.  Hip Extensor

     stand 12-18 inches from table

     bend at hips: hold onto the table

     slowly lift one leg straight backwards; hold position

     slowly lower leg

     repeat with other leg

2.  Hip Abductor

     stand near table; hold onto table

     move straight leg sideways away from body; hold position

     slowly lower leg

     repeat with other leg

3.  Knee Extensor

     sit in a chair with your back and hips against back of chair.

     keep knees at 90 degree angle, resting toes on ground

     in a 1-2 up count,  extend your left leg straight out parallel to the ground

     pause for 1 second

     in a 1-2-3 down count, slowly lower your leg back to 90 degrees

4.  Knee Flexor

     stand behind chair, resting hands on back of chair, facing forward, keep head in line with spine, place feet shoulder-width apart, pelvis level with knees slightly bent

      in a 1-2 up count, bend left leg to bring up heel toward buttocks as high as possible

      pause for 1 second

      in a 1-2-3 down count, lower left heel to ground

5.  Inner Range Quadriceps

     sit on ground with knee bent over a rolled up towel

     tighten up knee muscles and lift heel off ground; keep knee on rolled up towel

     hold for 5 seconds, getting heel as high as possible

     start with large rolled up towel and gradually decrease size of roll

6.  Ankle Dorsiflexor

     sit on chair with feet touching floor

     leave heel on floor and tap toes up and down

     Alternative – using elastic stretch band of comfortable resistance

     sit on the floor with legs straight out in front

     anchor elastic band to a chair or table leg and wrap around foot

     pull toes toward you and slowly return to start position

7.  Ankle Plantar Flexion

     sit on chair with feet touching floor

     leave toes on floor and lift heel up and down

     Alternative with elastic band

     wrap elastic band around foot and hold the ends in your hands

     gently point toes and slowly return to start position

Insight 4: Anti-aging benefits of aerobic and stretch exercises

Exercise, Individual controls aging, , , , , , , ,

Aging of heart, blood vessels, chest, lungs and brain is significantly retarded with aerobic

A program of progressive resistance training (PRT) that reduced age-dependent loss of skeletal muscle mass and strength was discussed in the previous blog.  Three other types of exercises of considerable importance are  1)  aerobic, 2) stretch and 3) balance exercises, and together with PRT, provide a comprehensive exercise program for the older adult.  As with PRT, these additional 3 exercises  have been validated in clinical trials to retard specific age changes and enhance physical function.  For that reason, this blog will focus on the benefits of aerobic and stretch exercises and define how each should be performed to achieve maximal health results.  Balance exercises improve different age-related deficits and consequently will be discussed separately in another blog.

Age changes prevented/slowed with aerobic and stretch exercises

One’s ability to engage in physical activity or activities above rest e.g. climbing stairs, shopping, catching a bus, running on the track, requires enhanced coordinated efforts from many organ-systems.  Consider the most noteworthy changes:

What happens in the heart

 a) there is a stronger and more forceful heart beat to assure that more blood is pumped to key organs e.g. skeletal muscles, lungs and also the heart;

What happens in the blood vessels

 b) there is an improve compliance (flexibility) of blood vessels to keep blood pressure adequate for delivery of  elevated levels of oxygen and removal of carbon dioxide and other waste products;

What happens in the lungs

c)  there is an increase the rate and depth of each breath by forceful contraction of the chest, diaphragm and abdominal muscles to capture more oxygen and expel more carbon dioxide;

What happens in the leg muscles

 d) there are more rapid and forceful contractions/relaxations of mainly the large skeletal muscles of the legs. 

Peak performance declines with age but more so with a sedentary lifestyle

This multiplicity of events, at its peak performance level for any one person, is referred to as maximal oxygen consumption. Since maximal oxygen consumption can be measured fairly accurately, it has been for decades a popular number for scientists to assess.  It basically represents the level of physical fitness of an individual.  Thus there is a considerable amount of information defining the change in maximal oxygen consumption (or fitness) over time.  In particular, fitness declines with age in everyone but significantly less so in older adults engaged in an aerobic program for most of their adult life.  Regrettably and because of this, elderly with a sedentary lifestyle will experience a dramatic inability to engage comfortably in all physically activities above rest. Physical activity will be cut short by rapid onset of fatigue. 

Without chronic aerobic exercise, heart, blood vessels, lungs and leg muscles slowly fail

In the absence of aerobic exercise, an age-related decline in VO2max occurs for several reasons:  both the heart and large blood vessels (carotids, aorta) become less compliant e.g. stiffer over time.  This causes the heart to work harder even at rest.  Additionally, the small blood vessels with time lose their ability to produce an essential vasodilator (EDRF) that had assured increased blood flow when younger.  Without EDRF, key organs (heart, lungs, brain, skeletal muscles) are deprived of requisite oxygen and nutrients and hence tissues/organs cannot handle the demands inherent in physical activity.  The lungs and chest also become harder to  inflate and deflate due to factors such as  loss of chest and lung flexibility but also muscle weakness (dynapenia).   These are  guaranteed age-associated changes in the absence of aerobic exercises.

Proven benefits of aerobic exercise

Unlike resistance exercises, the number of older adults that participate regularly in aerobic exercises is significantly greater (approximately 40% age 65-74, 30% 74-84 and 20% >85*) and this is a good thing.   However, considering the multitude of benefits, this degree of participation  remains disappointing. 

Aerobic exercises include activities such as jogging/running (outside or treadmill), cycling (outside or stationary), swimming, dancing, and walking.  Results of literally thousands of interventional clinical trials, observational and epidemiological studies point to an abundance of benefits of  regular aerobic exercise.  All the benefits listed have been documented numerous times.  Benefits of regular aerobic exercise are:    

Blood vessel transport blood more easily

1)  reduction in age-dependent stiffening of major arteries allowing greater capacity of arteries to stretch and secondarily to reduce the workload on the heart; lower resting heart rate promoting more efficient heart pumping

Exchange of nutrients, gases and waste products is more efficient

2)  tissues/organs are healthier due to better flow of oxygen in and waste products out resulting in less inflammation and cellular damage; especially beneficial to the brain leading to improved cognition, reduced risk of mild cognitive impairment, depression, anxiety

Control of blood sugar is improved; fats and “bad” cholesterol are lowered

3)  metabolic benefits of improved blood sugar control, reduction in body fat, favorable lipid profile with low levels of free fatty acids and higher levels of HDL (“good cholesterol”), weight maintenance or loss

More energy for all activities

4)  decrease in fatigue (the older adult tires less easily, remains physically active for longer periods of time)

Reduced levels of stress

5)  increase in ability to handle stress ( the older adult exhibits better outcomes following surgery e.g. shorter hospital stay, faster recovery) 

Reduction in risk for many diseases

6)  reduction in risk for diseases including cardiovascular disease, type 2 diabetes, Alzheimer’s disease and frailty (condition of increased weakness predicting imminent death

Assured independence and quality of life

7)   increase in quality of life supporting continued independence 

Aerobic exercises – how to get the most out of them

Each person should select the aerobic activity of interest.  For sedentary elderly initiating a program, it is prudent to first discuss an exercise program with your physician and then to begin slowly with a progressive stepwise increase in intensity.  As with PRT, the goal with aerobic exercises is to gradually do more by increasing time or energy spent.   As several recent studies have shown, anti-aging health benefits are proportional to the input. 

Ideally, aerobic exercises are performed five times a week for 30 minutes or more depending on the level of intensity (55-90% of a maximal heart rate or 12-and above on a perceived exertion scale given in Table 1 in PDF 1).  Maximal heart rate can be calculated by multiplying one’s age by 0.7 and subtracting that number from 208.  Table 2 in PDF 1 shows the required exercise duration based on intensity.

PDF-1-Borg-Scale-Aerobic-intensitiesDownload

An alternative to standard aerobic exercise is high intensity interval training (HIIT)

The Mayo Clinic*** in an impressive study about 3 years ago reported that 12 weeks of high intensity interval training (HIIT) provided huge benefits for the elderly.  In this study, volunteers in 2 different age groups  (18-30 yrs and 65-80 yrs) performed the following:  a) high intensity interval training, 3x weekly + 2x weekly of treadmill walking, b) resistance training, 2x weekly and c) sedentary period followed by combined training of moderate-intensity aerobics, 5x weekly + 4x weekly resistance training . 

HIIT in this study consisted of stationary cycling for 4 minutes at > 90% maximal oxygen intake (high intensity), followed by 3 minutes reduced intensity (no resistance), followed by 4 minutes of maximal oxygen intake, followed by 3 minutes of no resistance.  This was repeated two more times yielding total time investment of 25 minutes.   

Benefits of HIIT

HIIT results outperformed the other two exercise protocols by providing the following:

a)  highest level of improved cardio-respiratory fitness (optimal heart and lung function), increased insulin sensitivity (lower blood sugar levels), enhanced mitochondrial respiration (improved function of cells with evidence of reversal of age changes), and decreased fat-free mass  (loss of body fat) in both young and older age groups.

b)  similar but lesser effects were observed in groups undergoing resistance training and combined training.  It is concluded that HIIT is a more effective means of reversing aging of the heart, blood vessels, chest , lungs and skeletal muscles.  Thus it can substitute for vigorous exercise listed in Table 2.

Benefits of stretch exercises

Performance of stretching or flexibility exercises is the best way to:

a)  improve range of motion of the joints,

b)  increase agility and speed in physical activities,

c)  reduce injury of muscles and joints.

In addition to the above, other benefits from adherence to a stretching protocol have been observed:  lowering of blood sugar in individuals with Type 2 Diabetes, reduction in frequency and intensity of nocturnal leg cramps.

Stretching to accompany aerobic exercises

What are stretch exercises?

Stretch exercises are an excellent companion to aerobic exercises.  Performance frequency for stretch exercises is under debate.  Suggestions range from twice daily every days to the traditional advice of stretching before and after aerobic exercises (5 days a week).  Recently, it was found that maximal benefit is achieved with stretching after a session of aerobic exercise and in this case, a warm-up (exercising at a low intensity) prior the aerobic exercise session is recommended to replace the stretch exercises.  There are two types of stretch exercises:  static and fluid (dynamic).  Static stretching is maintaining a slow and controlled continuous tension to a muscle group(s) while fluid stretching requires tension on specific muscle groups while taking them through a full range of motion.  

How to get the most out of stretch exercises

Total stretching time with a variety of stretches is the important determinant that improves range of motion and reduces injury.  This is more influential than the length of time a stretch is held or the number of repetitions.  Optimal stretch time per muscle group is generally 30 seconds.  As with other exercises, the gain in benefit (range of motion, flexibility etc) with stretching declines over time when the protocol is stopped.   

There are many static and fluid stretches for both upper and lower body muscles.  The following videos provides excellent examples to incorporate into a stretch protocol following an aerobic workout.

Videos demonstrating stretch exercises

PDF-2-Selection-of-stretch-videosDownload

* Data from surveys and household interviews (2013-2015) reported by Centers for Disease Control and Prevention September 23, 2016 / 65(37);1019

** Borg GA.  Psychophysical bases of perceived exertion.  Med Sci Sports Exerc 14:377-381, 1982.

*** Robinson et al., Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans Cell Metabolism 25: 581–592, 2017

Insight 3: Ways to retard skeletal muscle aging

Exercise, Individual controls aging, , , ,

Regular Progressive Resistance Training is the answer

So what can the older adult do to assure continued independence, normal weight and avoid a fall and Type 2 Diabetes?  Results of over hundreds of clinical trials conclude that regular progressive resistance training (PRT) is the answer.  This is the way the to retard skeletal muscle aging. Although this strategy has been in the scientific literature for near 30 years, surprisingly and sadly, very few adults follow an exercise program that includes resistance exercises (in the US population, an estimated 5% participate in resistance exercise versus more than 50% that engage in an aerobic regimen e.g. walking, swimming, jogging).  An additional piece of advice, stemming directly from clinical trial results, recommends the ingestion of 20-35 grams of quality protein post PRT workout to maximize the benefit gained from the resistance training alone. 

Progressive resistance training to retard skeletal muscle aging?

So what exactly is progressive resistance training (PRT)?  Simply, it is strength and speed training against a resistance which is either free weights e.g. dumbbells or barbells, weight machines (gravity resistance), calisthenics e.g. squats (body and gravity resistance) and/or use of resistance elastic bands or tubes.   In starting a program of PRT, consideration is given not only to the  type of resistance as just indicated but also, target muscles, frequency of exercise, intensity, and repetitions. 

Liu and Latham (2015)* reviewed 121 clinical trials with over 6,000 participants and concluded  that ” Doing PRT two to three times a week can improve physical function in older adults, including reducing physical disability, some functional limitations (i.e. balance, gait speed, timed walk, timed ‘up-and-go’, chair rise; and climbing stairs) and muscle weakness in older people.”  The average age in these studies ranged from 61 to 88 years.   Approximately half of the studies enrolled healthy sedentary older adults; the remainder were comprised of older adults with physical disabilities or limitations.   PRT lasted anywhere from 10 weeks to 2 years, targeting different muscle groups with increasing intensity.   It is noteworthy that older adults of any age, with or without physical limitations, will benefit from PRT.

A reasonable progressive resistance training program

What is an example of a successful PRT program?  A reasonable PRT program, based on results of interventional studies discussed above, has been developed for beginners, intermediate and advanced participants (Law et al., 2016)*.  The program is given below (PDF 1).  Target muscles are those of the chest, back, arms, shoulder, upper legs and lower legs.  For beginners, the program is 8 weeks in duration, twice weekly. Phase 1 (2 weeks) requires exercises at an intensity of 50-60% of one maximal repetition (RM) with performance of one exercise set with 12-15 repetitions.  For weeks 3-8,  the intensity increases to 60-69% of 1RM, the repetitions increase to 18, and a new exercise set is added. 

Ideally start with weight machines and trainer

Law et al., (2016) favors starting with weight machines and ideally a trainer to assure that the correct form is achieved for each exercise.  It is also advisable to discuss a new exercise program with your physician before setting forth.  The sample program for intermediate and advanced PRT modifies the beginner program and adds new exercises with increases in both intensity, sets and repetitions.  In lieu of weight machines, there are reliable established  free videos on strength training with dumbbells (PDF 2), and alternative exercises e.g. calisthenics and elastic bands (PDF 3)).  Remember the program must be progressive to be of benefit and hence must increase in intensity over time.

Progressive resistance training and protein supplementation are proven means to minimized age-associated sarcopenia and dynapenia.

To maximize the benefits of PRT, findings from numerous studies, albeit with a small number of volunteers, show that consumption of high quality protein e.g. soy or whey (20-35 gm) or essential amino acids leucine and isoleucine (3.5 gm) stimulates skeletal muscle formation and leads to better outcomes (mass, strength, performance) than PRT without protein supplementation.  Leucine and isoleucine cannot be synthesized by the body so both must be ingested. Leucine and isoleucine are the amino acids most adept at encouraging exercised muscles to up their production of major muscle proteins e.g. myosin.  Protein supplementation is based on studies with volunteers, 55-85 years of age, of various weights (normal to obese) who performed resistance exercises  (hand held weights and machines) for 10-26 weeks, 2-3 x per week, multiple target muscles with 3 sets of 8-12 repetitions at 70-85% maximal repetition.  

Do not forget protein supplementation

PRT plus protein supplementation is the anti-aging strategy that is definitely in sync with living a longer healthier life.  Consider the wealth of benefits from this strategy:  strength to perform all desired daily activities, avoidance of physical disabilities, maintenance of ideal weight or weight reduction, adequate handling of sugars/carbohydrates, avoidance of falls and an acceptable response to the cold.  These are advantages that guarantee continued independence and optimal quality of life.  These are benefits that should motivate every adult over 50 to participate in this strategy. 

Progressive resistance training is part of 4-prong exercise program for the older adult

PRT is one part of a 4-prong exercise program validated to minimize age changes.  PRT is of high priority considering the plethora of positive outcomes for the older adult.  However, the three other components (aerobics, balance and stretch ) of the 4-prong exercise program provide different but equally important advantages and will be discussed in my next blog.

Resistance exercise with machines

PDF 1 (Resistance exercises with machines) describes evidenced-based PRT proposed by Law et al., (2016)**   It consists primarily of exercises using machines one would find in a fitness gym or YMCA.  There are three progressive levels, beginner, intermediate and advanced that progress the individual from 1 set of 12 repetitions to 3 sets of 10 repetition over a period of 32 weeks.  Machine-dependent exercises is probably the easiest way to initiate PRT but this approach does require a gym membership.  The main advantage is that experienced personnel are available to assist with the use of each machine.  To provide a level of familiarization, PDF 1 also contains videos that demonstrate the proper execution of each exercise with the particular machine. 

Resistance exercises with dumbbells

PDF  2 (Resistance exercises with dumbbells) follows the progression of strength training defined by Law et al., in PDF 1 but substitutes dumbbells (hand held weights).   The advantage of these exercises is that they can be done at home.  However, one must purchase a set of dumbbells.  I have added videos for all of these exercises since it is essential that they be performed exactly as described to gain the most benefit and avoid injury.

Alternative workouts

PDF 3 (Alternative workouts) list 7 different workouts ranging in time and difficulty, available on line that one may also follow and that can be performed at home.  Although none per se have been subjected to a clinical trial they contain exercises providing benefits comparable to those defined in PDF 1 and 2.  The key point to remember is that resistance exercise needs to be progressive.  Thus either increase in weight or resistance and/or number of repetitions is required to yield strength benefit.

*  Liu C-J, Latham NK.  Progressive resistance strength training for improving physical function in older adults.  Cochran Database Syst Rev: July 8 (3): CD002759, 2009.

** Law TD, Clark LA, Clark BC.  Resistance exercise to prevent and manage sarcopenia and dynapenia. Annu Rev Gerntol Geriatr 36: 205-228, 2016.

PDF-1-Resistance-exercise-with-machinesDownload
PDF-2-Resistance-exercise-with-dumbbellsDownload
PDF-3-Alternative-workoutsDownload