What is aging?

Aging is the accumulation of changes in an organism or object over time.

Aging in humans refers to a multidimensional process of physical, psychological, and social change.

Some dimensions of aging grow and expand over time, while others decline.

Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand.

The world’s population is aging and along with global aging come special health challenges.

How do you measure age?

Chronological age does not correlate perfectly with functional age, i.e. two people may be of the same age, but differ in their mental and physical capacities.

Each nation, government and non-government organization has different ways of classifying age.

Divisions are sometimes made between the young old (65–74), the middle old (75–84) and the oldest old (85+).

New England centenarian study

There are currently ~1,600 centenarians, 500 children (in their 70s and 80s) and 300 younger controls. Amongst this group is the largest sample in the world, by far, of supercentenarians (age 110+ years) - there are about 107 of these oldest of the old subjects in the study.

Global median ages

Source: CIA World Factbook 2009.

Young children and older people as a percentage of global

population

Source: UN Department of Economic and Social Affairs.

Population aging

Population aging is the increase in the number and proportion of older people in society.

Population aging has three possible causes: migration, longer life expectancy (decreased death rate), and decreased birth rate.

Health care costs and aging

Older people have different requirements from society and government as opposed to young people, and frequently differing values as well.

The aged use up health care dollars and present a huge opportunity for health promotion.

Source: Congressional Budget Office.

Cellular definition of aging

Cellular aging is a phenomenon where isolated cells demonstrate a limited ability to divide in culture (discovered by Leonard Hayflick in 1961).

In humans between 20 and 35 years of age, cellular aging and cellular losses occur in the organs including the brain, skin, and muscle.

Aging is characterized by the declining ability to respond to stress, increasing imbalance of biological processes and increased risk of disease.

Scientists now regard aging in a similar fashion to other genetically influenced conditions like obesity and overweight as modifiable by balanced nutrition and a healthy active lifestyle.

Why cells age

Source: Wall Street Journal.

Example: fish oils which balance immune function can slow

telomeric aging

Source: Journal of the American Medical Association.

Calorie restriction

Increased inflammation from rapid growth of abdominal fat in storing calories through interaction with the immune system leading to systemic inflammation and local inflammation which accelerate aging may be one explanation.

When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet.

These ideas are being studied to increase maximum lifespan in humans.

Abdominal fat is an organ promoting inflammation

Source: Lancet.

Life-span increases and beneficial health effects by organism

The retardation of aging in mice by dietary restriction:

longevity, cancer, immunity and lifetime energy intake

Female mice from a long-lived strain were fed after weaning in one of six ways: group 1) a nonpurified diet ad libitum; 2) 85 kcal/wk of a purified diet ( 25% restriction); 3) 50 kcal/wk of a restricted purified diet enriched in protein, vitamin and mineral content to

provide nearly equal intakes of these essentials as in group 2 (55% restriction); 4) as per group 3, but also restricted before weaning; 5) 50 kcal/wk of a vitamin- and mineral-enriched diet but with protein intake gradually

reduced over the life span; 6) 40 kcal/wk of the diet fed to groups 3 and 4 ( 65% restriction). Mice from groups 3-6 exhibited mean and maximal life spans 35-65% greater than for group 1 and 20-40% greater than for group 2. Mice from group 6 lived longest of all. The longest lived 10% of mice from group 6 averaged 53.0 mo which, to our knowledge, exceeds reported values for any mice of any strain.

Sources: UCLA Department of Pathology, UCLA Mental Retardation Research Center.

Mouse diets and survival rates over time

The mice ate diet 2 (35% casein) from weaning until 4 mo, a 25% casein diet from 4 until 12 mo, 20% casein from 12 until 24 mo, and 15% casein from 24 mo until death.

Diet 2 was modified to form the 15, 20 and 25% casein diets by replacing casein with carbohydrate.

CR effects on fat cells

Metabolic reprogramming is a prominent feature of the CR effect in Fat Cells (White Adipose Tissue or WAT) with increased expression of genes involved in the glycolytic pathway, the lipolytic pathway, amino acid metabolism and mitochondrial metabolism (Higami et al. 2004).

In addition to this striking activation of energy metabolism, there was a marked reduction in the expression of genes involved in inflammation in WAT (Higami et al.2006).

These alterations in WAT may provide an explanation for how CR delays the onset of age-associated diseases that have a basis in systemic inflammation, and points to a potential role for WAT derived factors in the aging process

Genes linked to networks

Source: California State Polytechnic University, Pomona.

Many chronic nutrition related diseases originate from

metabolic imbalance

What is happening here? Can we identify, quantify and modulate these processes?

Source: European Nutrigenomics Organisation.

Aging brain and memory

A steady decline in brain functions are seen starting about age 30 especially in many types of memory with aging.

There are changes to the brain though loss of brain cells is minor until age 20. The brain is made of nerves which send out branches called axons. These axons are like wires that conduct electricity and they are coated with a fat called myelin. The length of these wires in the brain shorten 10% per decade after age 20.

However, inflammation is the likely culprit in serious loss of memory function.

Aging and the skin

Cell damage caused by metabolic processes, free radicals and cosmic irradiation.

Photodamage includes appearance of wrinkles, pigmented lesions, actinic keratoses and patchy loss of color.

Sunblockers, Vitamins A,C, E, Aloe, Antioxidants with a Healthy Lifestyle and Balanced Nutrition, especially protein.

Aging and muscle loss

There is a loss of muscle mass with aging.

There is also a loss of muscle strength.

The nerves to the muscles decrease in number with aging.

Where does the extra weight come from?

Answer: FAT

Difference between muscle and fat cells

The best correlate of Resting Energy Expenditure is the Lean Body Mass, so when muscle is lost in sarcopenic obesity, the Resting Metabolic Rate is reduced and weight gain occurs without a large increase in food intake.

Source: ADAM.

Muscle Burns 30 kcal/kg

Fat Burns 6 kcal/kg

Utility and limitations of BMI

Permits population-based studies of trends in obesity and is used for clinical guidelines.

Does not correlate well with fat mass in both over-muscled (athletic) and under-muscled (sarcopenic) patients.

Does not reveal differences in fat distribution (visceral vs. subcutaneous).

Does not measure fat directly but correlates with body fat over thousands of average patients.

At any given BMI, women have more fat than men

Lean body mass is 70% water and conducts electromagnetic

energy, but fat does not

Magnetic Resonance Imaging (MRI)

Even if you are thin, you can be fat

MRI reveals fat around the Heart, Liver and Intestine in Individuals with Normal Waist Circumference.

Of the women scanned by Bell and his colleagues, as many as 45% of those with normal BMI scores (20 to 25) actually had excessive levels of internal fat.

Among men, the percentage was nearly 60%.

Waist circumference = 33 inches

Intra-abdominal fat

Macrophage and the innate immune system pro-inflammatory cells ingress mediates the inflammatory state of adipose tissue

Sarcopenic obesity

Loss of muscle protein due to inadequate protein intake during dieting leads to decreased muscle mass (sarcopenia) and increased fat mass (obesity) which may contribute to difficulties with physical function.

Compared with women with a healthy body composition, sarcopenic-obese women had a 2.60 higher odds of having difficulty climbing stairs and a 2.35 higher odds of having difficulty going down stairs (all P < 0.05).

Source: American Journal of Clinical Nutrition.

Normal Muscle to Fat Ratio

Increased Fat/Reduced Muscle = Sarcopenic Obesity

Role of protein: providing amino acids

Building blocks for new proteins

Providing energy – limited (~15% of daily kcal), but specific (muscle, liver, brain, pancreas, adipose)

Metabolic signals

Tryptophan serotonin neurotransmitter

Arginine nitric oxide vascular function

Leucine mTOR protein synthesis

Schematic of protein breakdown & synthesis

Interaction of physical activity and nutrition

Leucine and protein synthesis

Leucine in different food components

6.8 8.0

8.8

10.9

0

1

2

3

4

5

6

7

8

9

10

11

Wheat Gluten Soy Protein Isolate Egg White Solids Whey Protein Isolate

(g / 100 g protein)

Protein needed to stimulate muscle protein synthesis

37

31 28

23

0

5

10

15

20

25

30

35

40

Wheat Gluten Soy Protein Isolate Egg White Solids Whey Protein Isolate

Grams

The limit to protein utilization

Muscle protein balance

Source: Nutrition.

Bal

ance

Time

Meal Meal Meal

Protein accretion

Protein loss

Protein synthesis

Protein breakdown

Summary: protein is about each meal

For adults, particularly during energy restriction

Daily amount:

Greater than 1.2 g/kg/day

25 g of protein at each meal

Key meal to correct is breakfast

Muscle protein balance around meals

Bala

nce

Time

breakfast lunch dinner

Protein accretion

Protein loss

Protein synthesis

Protein

breakdown

Meal patterns

Breakfast

protein

Lunch

protein

Dinner

protein

Breakfast

~10 g protein

Lunch

~20 g protein

Dinner

~60 g protein

~30 g ~30 g ~30 g

Balanced Protein Distribution Unbalanced Protein Distribution

{Maximum protein synthesis}

WHO protein recommendation

The World Health Organization (WHO) recommends that dietary protein should account for ∼10–15% of energy intake when in energy balance and weight stable.

Average daily protein intakes in various countries indicate that these recommendations are reflective of what is being consumed worldwide.

Given the range of the normal protein intake, meals with on average 20% to 30% of energy from protein are representative of a high protein diet, when consumed in energy balance.

What is a high protein diet?

Accordingly, we consider on average ∼10–15% of energy intake from protein, when in energy balance and weight stable as a normal protein intake, and >15% of energy intake from protein, when in energy balance and weight stable, as a high protein intake.

When subjects are not in energy balance, the relative percentages of protein intake shift, and preferably also absolute amounts of protein intake should be considered.

You can control your health

Only 30% of how

you

age is

determined by

your genes.

The other 70% is in

your hands.

Nutrition

&

Exercise

Genes

CaP prevalence increases as testosterone (T) levels decline

Low T associated with higher stage and grade of tumor

40-49 50-59 60-69 70-79

CaProstate

Testosterone Levels

Low testosterone levels and diabetes/metabolic syndrome

Three major studies with > 2,800 patients

Those in lowest T quartile over 11 years had 2.3x higher risk of metabolic syndrome and type 2 diabetes

Sources: Diabetes Care, Journal of Clinical Endocrinology & Metabolism.

Men with low T = More likely to develop

metabolic syndrome or type 2 diabetes

Low T & mortality

VA population > 40 yrs age

T < 275 ng/dl

Source: JAMA Internal Medicine.

Effect of TRT on HbA1c

Diet + exercise (56 y)

Diet + exercise + T gel (57y) p < 0.05

T<345 ng/dL 6.5<HgA1c<9

Source: Journal of Andrology.

Waist circumference & body weight in 162 obese hypogonadal

men (n = 261) treated with TU for up to 5 years

Source: Journal of Sexual Medicine.

90

95

100

105

110

115

Waist Circumference (cm)

Weight (kg)

baseline 1 year 2 years 3 years 4 years 5 years

*#

*#

*# *#

*

*p<0.0001 vs. baseline; #p<0.0001 vs. previous year AGE = 59.5

T < 350 ng/dl

TRT & mortality

VA population > 40 yrs age

Source: JCEM.

+ T

- T < 250 ng/dl

Increase in T prescribing

Source: Medical Journal of Australia.

CANADA

US

UK

n = 1,223

n = 7,486

Association of testosterone therapy with mortality, myocardial

infarction, and stroke in men with low testosterone levels

n = 23,173 cor. angio 2005-2011

1,223 received TRT

1,008 (82.4%) filled > 1 Rx of T

≥ 374 of these 1,008 did not have a repeat serum T

Source: JAMA.

USC School of Gerontology Longevity Institute

Source: Science.

How do we live a long, healthy life?

World’s “Oldest Woman” celebrates 115th birthday in Los Angeles

Never drank or “fooled around”

No bacco, no tobacco, no venere

(No wine, no tobacco, no venus)

Salvatore Caruso, Calabria, Italy

Age 108

Jean Calment in France: lived to 122 and smoked until 100

She attributed longevity to olive oil, red wine and chocolate

Dietary proteins and sugars activate the growth genes that

promote aging and diseases

Tor-S6K cAMP-PKA ??

Aging + Diseases (cancer, diabetes, etc)

How do we live a long, healthy life?

The longevity diet (based on epidemiological, clinical, centenarian, and animal studies)

Mostly plant-based (vegetables, legumes, fish, whole grains)

Low protein intake until age 65-70 (0.37 g/lb/day), then gradually increase protein intake preferably from plant-based sources and fish (0.45-0.5 g/lb/day)

High levels of complex carbohydrates and healthy fats (olive oil, nuts)

High nourishment (omega 3s, vitamins, minerals)

Occasional periods of medically supervised fasting + only 2 meals/day for people who cannot maintain a healthy weight (up to age 70-75)

Longevity and fitness

Benefits of strength training:

Physiological

Psychological

Preventative

Restorative

Source: Wikipedia.

Get with the program

What goes into a well-rounded fitness program?

Strength training

Cardiovascular training

Corrective strategies

Soft tissue work (by a licensed therapist)

Source: Wikimedia Commons.

Equinox/UCLA study on supervised vs. self-directed training

Effect of supervised, periodized exercise training versus self-directed training on lean body mass and other fitness variables in health club members

Participants

34 males ages 30-44 years old

Workouts 3x a week over 12 weeks

17 trained with personal trainers

17 self-trained

Source: Journal of Strength and Conditioning Research.

Equinox/UCLA study on supervised vs. self-directed training

This is what they found:

Source: Journal of Strength and Conditioning Research.

Variables Measured Personal Trainer Self-Trained

Lean Body Mass +1.3 lbs. No Change

Chest Press +49% +19%

Peak Leg Power +6% +0.6%

VO2 Submax +7% -0.3%

Leg Press Strength +38% +25%