1. Describe the anti-inflammatory effects of diet, exercise, and nutrition.

2. Discuss benefits of hormone replacement therapy, based on current data.

3. List therapeutic uses of stem cells.

4. Recognize unique challenges and needs of baby boomers in the management of hearing loss.

5. Counsel patients on prevention of hearing loss.

The Science of Anti-aging and Human Performance
Ron Rothenberg, MD, Clinical Professor of Family and Preventive Medicine, University of California, San Diego, School of Medicine, and Founder, California HealthSpan, Encinitas

Introduction: paradigm shifts—1) gene expression can be changed; 2) hormones; aging and degeneration may be due to hormone decline; hormone levels can be optimized; 3) chronic inflammation cause and effect of diseases of aging; optimizing hormones results in less inflammation; no increased cancer or cardiovascular (CV) risks; routes (eg, oral, transdermal) important; 4) adult stem cells act as “built-in repair system”; conventional medicine extends morbidity (eg, provides additional 5 yr in nursing home); aim for “rectangularization” (ie, staying strong, healthy, and happy as long as possible); compress morbidity and degeneration

Anti-aging preventive regenerative medicine: optimal lifestyle; cutting-edge technologies for early detection and prevention of age-related diseases; scientific, evidence-based, and well-documented in current medical literature; not alternative medicine and not purely aesthetic medicine

Lifestyle: diet, exercise, and stress reduction 80% of anti-aging medicine; customize programs for patients; laboratory testing—consider performing tests that are “conventionally not done very often”; testing for C-reactive protein (CRP) and homocysteine “exotic” 10 yr ago; test for inflammatory cytokines; nutrition and exercise programs should be personalized to patient’s genetics and laboratory tests; in stress reduction, lowering cortisol important; consider nutriceuticals (eg, vitamins), hormones, and use of adult stem cells (frozen and banked)

Inflammation: unified theory of wellness—chronic inflammation causes diseases of aging; providing anti-inflammation through lifestyle, nutriceuticals, and hormones can lead to wellness, peak performance, health, and happiness; antagonistic evolutionary benefit—eg, genes for type 2 diabetes may have improved survival in ancestors who lived in sparse environments with small amounts of food, but genes harmful to modern lifestyles

Nuclear factor (NF)-kappa β: cytoplasmic element that activates cyclooxygenase (COX) and lipoxygenase (LOX) enzymes; COX and LOX enzymes transform arachidonic acid (AA; omega-6 fatty acid) to eicosanoid hormones that lead to inflammation (eg, thromboxane A2 involved in atherosclerosis); inflammatory process can be stopped with eicosapentaenoic acid (EPA; in fish oil); NF-kappa β activated by lifestyle, stress, chronic infections, chronic periodontal disease, high glucose and insulin, lack of hormones and exercise, trans fats, and CRP; balancing estradiol and progesterone, vitamin D, and resveratrol prevents NF-kappa β from activating cytokines (eg, interleukin [IL]-6, tumor necrosis factor [TNF]-α) that promote COX and LOX enzymes

Exercise and stress reduction: promote anti-aging; reduce inflammation; exercise—increases production of growth hormone (GH) and testosterone; improves cognitive function; lowers inflammatory markers (eg, CRP); stress reduction—lowers cortisol (protects hippocampus from cognitive impairment; reduces atherosclerosis; produces anticancer hormones [eg, 2-methoxyestradiol])

Eicosapentaenoic acid: omega-3 fatty acid; anti-inflammatory; study showed 80% reduction in sudden death rate; after 3 mo, 1 g of EPA and docosahexaenoic acid (DHA) reduced mortality after acute myocardial infarction (MI) by 41%; optimal daily dose of EPA and DHA, 4 to 8 g; AA to EPA ratio in populations—Inuit, 0.7; Japanese, 1.5; European, 5; American, 10 to 20; higher in populations with Alzheimer’s disease, attention-deficit/hyperactivity disorder (ADHD), and fatal MI

Vitamin D: produced endogenously; epidemic of low vitamin D in United States; inadequate production due to, eg, use of sunscreen; reference range of 25-hydroxyvitamin D, 33 to 100 nmol/L; data support anticancer and anti- heart disease effects, enhancement of immune system, and antiviral and antibacterial actions; necessary for building bone; prevents falls; reduces inflammation; antidepressive; 1100 IU/day shown to reduce cancer risk; sudden cardiac death 5 times higher (heart failure 3 times higher) in patients with vitamin D levels below reference range, compared to those with levels within reference range; few reported cases of vitamin D toxicity; dose needed by most patients to reach top of reference range, 10,000 IU/day

Resveratrol: polyphenol in red wine; associated with less heart disease, cancer, and inflammation; involved in genetic manipulation (eg, activates sirtuin genes that aid in calorie restriction); 100 to 200 mg/day shown to lengthen lifespan in several species

Homocysteine: inflammatory; high levels predict acute MI and osteoporosis; adequate vitamin B6 , B12 , and folic acid levels recommended; reference range of homocysteine, <12 µmol/L (speaker prefers <7 µmol/L)

Balanced hormone optimization: concept of restoring all hormones to level found in 25-yr-old; monitoring based on serum levels and clinical results; bioidentical hormones used; hormones can be synthetically produced, but should not be derived from other species (conjugated estrogens [eg, Premarin] derived from horses); harmonize testosterone, estrogen, progesterone, dehydroepiandrosterone (DHEA), pregnenolone, adrenal hormones (eg, cortisol), thyroid hormones, vitamin D, and GH; treat hormone deficiency

Testosterone: level of bioavailable testosterone in 50% of healthy men ≈60 yr of age would be pathologic in men 25 yr of age; total testosterone levels in world populations decline every year; andropause—declining testosterone in aging men; lethal disease; associated with diabetes, metabolic syndrome, cognitive dysfunction, CV disease, frailty, inflammation, cancer, and depression

Replacement therapy: men—does not increase risk for clinical prostate cancer, benign prostatic hyperplasia (BPH), or CV disease; dilates coronary arteries; reverses angina; prevents plaque rupture; reverses atherosclerosis; improves libido, erectile function, mood, memory, heart disease, and quality of life; low level of testosterone (eg, 200 ng/dL) necessary for prostate cancer to metastasize (higher levels [eg, 1000-1200 ng/dL] not shown to have greater effect on stimulation of prostate cancer); 10-yr prospective study of ≈11,000 men found that men with higher endogenous testosterone levels had lower mortality from CV disease and cancer; study of ≈3800 men found no association between risk for prostate cancer and hormones (eg, testosterone, estrogen); improves performance by building muscle, bone, and cartilage; improves glucose use, oxygen supply, and hemoglobin; study found testosterone alone produced more fat-free body mass than exercise alone; women—testosterone needed for well-being, strength, libido, and nipple and clitoral sensitivity; can improve syndrome of relative androgen deficiency; women’s testosterone levels ≈10% that of men; better athletic performance in women with higher levels

Female hormones: deficiencies can start years before menopause; low progesterone causes poor sleep, premenstrual syndrome (PMS), anxiety, insomnia, agitation, and swollen or tender breasts; low estrogen causes classic vasomotor symptoms (eg, hot flushes, night sweats), depression, cognitive dysfunction, decreased libido, vaginal dryness, and sleepiness; bioidentical hormones should be used for hormone replacement therapy (studies showed adverse effects of horse-derived estrogen); literature suggests replacement with bioidentical hormones does not increase risk for cancer or heart disease; doses should be individualized and titrated to woman’s physiology; higher exposure to progesterone (eg, pregnancy) over course of woman’s life reduces risk for breast cancer

Growth hormone: for treatment of GH deficiency; no increased risk for cancer with GH replacement therapy; GH replacement therapy improves brain function, bone, atherosclerosis, CV function, immune system, body composition, wound healing, exercise capacity, quality of life, and cosmetic appearance; GH level high at 21 yr of age; at 60 yr of age, 24-hr GH level same as in 20-yr-old with pituitary disease; 300 ng/mL of insulin-like growth factor 1 (IGF-1; indirect measurement of GH) normal for persons 20 to 40 yr of age, but indicates deficit in those >40 yr of age; consider other hormones

Thyroid hormones: patients with euthyroid laboratory test results and low free triiodothyronine (T3 ) clinically hypothyroid; patients feel better when T3 and thyroxine (T4 ) combined

Stem cells: embryonic stem cells derived from blastocysts; “once baby is born, they’re adult stem cells”; in United States, adult stem cells collected from umbilical cord in 5% of deliveries; stem cell divides and produces daughter cells; one daughter cell identical to mother cell, other daughter cell progresses “to becoming something else”; stem cells can be released and collected through intravenous (IV) line after stimulating marrow with granulocyte colony stimulating factor (G-CSF); quality and quantity of stem cells improved by better lifestyle, hormones, exercise, and nutriceuticals; endothelial progenitor cells biomarker of aging; study showed supplement consisting of blueberry, green tea, vitamin D, and carnosine improved stem cells; ongoing studies for treatment of autoimmune diseases (eg, end-stage lupus), heart disease, type 1 diabetes when diagnosed in first 3 mo, and type 2 diabetes; FDA-approved uses—wound and fracture healing; leukemia; multiple myeloma; radiation poisoning; study showed positive results (eg, fewer deaths and repeat MIs, less need for revascularization and rehospitalization for heart failure) when stem cells placed in coronary artery after reperfusion post-MI; near-future uses—neurologic repair; regeneration of organs and tissues

Conclusion: measure free hormone levels; look for inflammation and risk factors; gene analysis; cancer screening; reduce CRP, fasting insulin, and homocysteine levels; consider vitamin D, IL-6, TNF-α, and IL-1 β perform biologic age test (eg, measure reaction time, visual acuity, forced expiratory volume in 1 sec [FEV1 ]); develop customized program with ongoing monitoring and medical supervision

The Aging Ear
David A. Geddes, AuD, CCC-A, Supervisor, Department of Audiology, HealthPartners Clinics, Saint Louis Park, MN

Presbycusis: degenerative change in hearing that causes sensorineural hearing loss with age; caused by hair cell death or dysfunction, reduced fluid movement resulting from stiffening of structures in cochlea, and/or reduced neural transmission in auditory pathway; 30% to 60% of patients >70 yr of age have measurable hearing loss; risk for tinnitus increases with each decade of life

Hearing loss in baby boomers (41-59 yr of age): estimated 31 million people suffer from hearing loss (14.6% are baby boomers; nearly 30% >60 yr of age); longitudinal study suggests difficulty with hearing in subjects ≥50 yr of age increased from 9.2% to 18.0% between 1965 and 1994; prevalence of hearing loss and number of baby boomers increasing

Unique challenges and needs of baby boomers: increasing demands in workplace; working in noisier environments; working beyond 60 yr of age; more communication needs

Case examples: Joe Boomer—49 yr of age; normal low-frequency hearing; mild high-frequency hearing loss; hearing loss similar in both ears; often unable to hear coworkers; daughter complains that television set too loud; stressed about hearing; Joe Retired—75 yr of age; similar audiogram to Joe Boomer; did not report hearing problems; concerned with mild tinnitus; different complaints and needs due to different lifestyles; patients with mild hearing loss should be referred to audiologist

Common listening environments and comments: noisy offices; difficulty understanding in meetings; “my boss said I had to get my hearing fixed”; “my kids mumble and I cannot hear them”; “if I could retire, I wouldn’t need to get a hearing aid”

Risk factors: recreational music—nightclubs; personal music players (eg, iPods) or other personal headphones; hobbies—power tools; rifles; handguns; motorcycles; disease—history of ear infection; autoimmune disease; no adequate controlled studies show clear link between diabetes and hearing loss (some studies suggest microvascular changes that occur in cochlea can lead to hearing loss); treatment for disease—aminoglycoside antibiotics; chemotherapy; loop diuretics; other risk factors—presbycusis

Role of primary care clinician: screen or ask about hearing loss during physical examination; follow up on self- reports of hearing loss; ask about noise exposure; recommend and advocate hearing protection; encourage safe use of iPods; refer to audiologist if indicated

Ear protection: foam earplugs; custom-made ear protection—more comfortable; provides correct fit; custom plugs for musicians allow musician to practice and perform while affording adequate protection; hunters’ ear protection— electronic protective device activates when gun discharges

Maximum recommended listening duration for iPods: at 10% to 50% of maximum volume, no limit; at 60%, 18 hr; at 100%, 5 min

Role of audiologist: perform complete diagnostic evaluation of hearing; provide hearing solutions (eg, hearing aids); counsel on hearing conservation and protection; provide custom hearing protection; assess outer hair cell function of cochlea with autoacoustic emission technology (often first indicator of noise-induced hearing loss and ototoxic exposure; refer patients with normal hearing and significant complaints and risk factors)

Questions and answers: tinnitus—if underlying hearing loss present, correct hearing (with, eg, hearing aid) to mask and reduce tinnitus; turning on radio at night can help mask tinnitus; review patient’s medications; otosclerosis— conductive hearing loss involving middle ear; seen in aging women; progressive; cerumen removal during screening audiography—if nonoccluding (ie, tympanic membrane visible), “I wouldn’t worry about it”; iPods—maximum volume output of iPods, 100 to 115 dB; duration of use important