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Exceptional longevity: why some people live to be more than 100-year old

Interventions that promote longevity, remembered by mnemonic: DEEP purple - “eat colorful plant foods: Dietary modification, Exercise, active Engagement, Purposeful living (click here to enlarge the image).

Based on a Mayo Clinic Proceedings article (https://www.mayoclinicproceedings.org/article/S0025-6196(18)30792-4/):

Exceptional Human Longevity: the oldest old have an extreme phenotype of delayed onset of age-related diseases and/or resistance to lethal illnesses occurring earlier in life.

Centenarians have delayed onset of chronic diseases

During the span of human history the likelihood of living from birth to age 100 rose from 1 in 20 million to 1 in 50 as of year 1995 (for females in low-mortality nations such as Japan and Sweden). By 2009, this probability increased to 1 in 2. About 1 in 5,000 persons in the United States is a centenarian or older. Human longevity now exceeds 115 years. However, maximum life span has remained largely unchanged. There is a limit to human longevity, and it may be around 120 years.

In centenarians, the age at onset of common age-associated diseases is delayed: 43% of both male and female centenarians reach the age of 80 years before experiencing age-associated illness.

There is an absence of any disease diagnosis in some 15% and 30% of female and male centenarians, respectively, at the age of 100 years!

As many as 25% of centenarians are cognitively intact.

Geographic Clusters

Geographic Clustering of Exceptionally Long-Lived Individuals: Countries with the world's oldest populations in 2015: Japan, followed by Germany, Italy, Greece, Finland, and Sweden.

Long-lived Okinawans subscribe to the nutritional behavior of “hara haci bu” or “eat until you are only 80% full.” Their “rainbow diet” is based on diverse fruits and vegetables, with soy providing the bulk of protein intake. Their daily caloric intake is reduced, accounting for their low BMI of 20.

Life span is increased in regular churchgoers, whatever their faith. Seventh Day Adventists exhibit significantly lower levels of measured stress hormones.

Behavioral and environmental influences that may contribute to longevity in the so called “blue zones”:

- Eating in moderation, mostly plant-based diet. Small-portioned “regular” meals. Lighter meals at the end of the day.
- Purposeful living: life philosophy, volunteerism, “hard work” or “work ethic”
- Social support systems: interactions with family/friends, laughter/humor
- Exercise, especially walking, gardening
- Other nutritional factors: goat's milk, red wine, herbal teas
- Spirituality
- Maintenance of a healthy body mass index (BMI)
- Other possible factors: sunshine, adequate hydration, naps

Compression of Morbidity: diseases occur later in life. Fries' “compression of morbidity” hypothesis: chronic morbidity begins at a later age.

Why Are Some People Long-Lived?

Genes: Centenarians' offspring have an increased likelihood of surviving to 100 years and exhibit a diminished prevalence of age-associated diseases.

Environmental factors exert even greater effect than genes.

Sex Differences: Universally, women live longer than men. Despite the greater longevity of women, functional status is better in older men compared with older women.

Resiliency is the capacity to adequately respond to stressors. It helps resist age-related physiologic changes. Resiliency protects against insults that shorten life and health span. Resiliency can explain why some centenarians, despite onset of chronic disease before the age of 80 years, live exceptionally long.

How Is Exceptional Longevity Achieved?

Caloric restriction delays the aging phenotype in mammals. This is shown by abundant studies. Caloric restriction delayed the onset of diabetes, cancer, cardiovascular disease, and brain atrophy.

Reduced calorie intake by 20% to 60% retards aging. It only works if such reduction is quite substantial.

What about exercise? Regular physical activity promotes healthy human life span. However, it is unclear if exercise increases maximum longevity.

Normal body weight confers the most protection from mortality.

Active engagement and development of social networks and support systems confer longevity benefits. Lack of strong social relations is associated with a mortality risk roughly equivalent to smoking.

Interventions that promote longevity can be remembered by the mnemonic: DEEP purple - “eat colorful plant foods”:

- Dietary modification
- Exercise
- active Engagement
- Purposeful living

How to Measure Successful Aging?

Several algorithms have been proposed to estimate biological age. They are based on functional as well as biochemical measurements.

Biomarkers of Aging Processes and Longevity:

Disease-free survival or disability-free survival at 6-month intervals
Time to impairment in the next activity of daily living
Length of stay after hospitalization
Height, especially in men
Facial features
Gait speed, grip strength, muscle mass, mobility stress test
Daily and instrumental activities of daily living
Cognitive tests such as the Digit Symbol Substitution Test or Montreal Cognitive Test
Blood glucose or hemoglobin A1c, hypertension and elevated lipids, interleukin 6, insulin-like growth factor 1, and insulin-like growth factor binding proteins
CD4+, CD28− and CD8+, CD28− T cells; percentage of T cells that are naive vs memory (CD4 cells, CD8 cells)
Antibody response to annual influenza vaccination; delayed hypersensitivity skin test
Cataracts
Threshold for hearing high-pitched tones; tests of taste and smell
Tests of proprioception and balance
Forced expiratory volume in 1 second
Number of remaining teeth
One or two parents reaching 90 years of age
Educational attainment
More speculative: DNA methylation indices; senescent cell burden

References:

https://www.mayoclinicproceedings.org/article/S0025-6196(18)30792-4/

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For type 2 diabetes patients who require an injectable drug, GLP-1-based drugs are preferred over insulin

That's a pretty big change:

Diabetes Guidelines Updated: For patients with type 2 diabetes who require an injectable drug, a glucagon-like peptide 1 receptor agonist is preferred over insulin. https://buff.ly/2T0Kowc

Glucagon-like peptide-1 (GLP-1)-based therapies (eg, GLP-1 receptor agonists, dipeptidyl peptidase-4 [DPP-4] inhibitors) affect glucose control through several mechanisms, including:

- enhancement of glucose-dependent insulin secretion
- slowed gastric emptying
- reduction of postprandial glucagon and food intake

These agents do not usually cause hypoglycemia.

Short-acting GLP-1 receptor agonists have an effect on postprandial hyperglycemia and gastric emptying:

- Exenatide twice daily. Exendin-4 is a naturally occurring component of the Gila monster lizard saliva and shares 53 percent sequence identity with GLP-1. Exenatide (half-life 2.4 hours) is synthetic exendin-4. Brand Names: Bydureon; Byetta Pen.

- Lixisenatide is a GLP-1 receptor agonist that shares some structural elements with exendin-4. Compared with native GLP-1, it has a prolonged half-life (2.7 to 4.3 hours). Brand Names: Adlyxin.

Long-acting GLP-1 receptor agonists have a greater resistance to dipeptidyl peptidase-4 (DPP-4) degradation. They activate the GLP-1 receptor continuously and have a prolonged half-life, thus allowing for once-daily and even once-weekly subcutaneous injection. They have a marked effect on fasting glucose.

- Exenatide once weekly is a sustained-release formulation of the short-acting subcutaneous exenatide.

- Liraglutide is GLP-1 receptor agonist which binds to serum albumin, resulting in slower degradation (half-life 11 to 15 hours) and allowing for once-daily, subcutaneous dosing. Brand Names: Saxenda; Victoza.

- Dulaglutide is a long-acting GLP-1 receptor agonist with structural modifications to prevent degradation by DPP-4 and to prolong its half-life. The half-life of dulaglutide is approximately five days, which allows for once-weekly administration. Brand Names: Trulicity/

- Semaglutide is a long-acting GLP-1 receptor agonist (94% homology with native human GLP-1) with structural modifications to reduce renal clearance and decrease degradation by DPP-4, resulting in half-life 155 to 184 hours, thus allowing for once-weekly, subcutaneous (or potentially once-daily, oral) dosing. Semaglutide is the only GLP-1 receptor agonist that has shown to be effective when given orally. Brand Names: Ozempic.

Based on studies, liraglutide or semaglutide are the preferred options.

The medications have a US Boxed Warning for Thyroid C-cell tumor risk.

References:

https://www.jwatch.org/fw114893/2018/12/19/diabetes-guidelines-updated
http://care.diabetesjournals.org/content/42/Supplement_1
https://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus

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Piriformis muscle syndrome remains controversial and diagnosis is difficult

Piriformis syndrome is a controversial entrapment neuropathy

What is  piriformis muscle?

The piriformis muscle is a small but important external rotator of the hip that crosses the sciatic nerve and is believed by some to cause sciatica-type pain when it compresses the nerve. However, the existence of this so-called "piriformis syndrome" remains controversial and diagnosis is difficult.

Controversy is due to the limited research about the condition and the difficulty of making the diagnosis, particularly as symptoms mimic many other more common diagnoses.

How common is it?

Piriformis syndrome may account for 0.3-6% of sciatic-like syndromes.

What causes it?

The sciatic nerve normally passes inferior to the piriformis muscle. Entrapment of the sciatic nerve may develop following trauma to the buttocks or piriformis muscle strain causing scarring and fibrosis around the nerve, or due to the structure of the piriformis, such as when branches of the nerve pass through a bifid piriformis muscle.

During downhill running or sprinting, the piriformis muscle undergoes eccentric contraction and some runners may develop the syndrome via this mechanism.

The activities involved may include running, where the gluteus medius and tensor fascia lata are activated in the stance phase, but more often sports requiring cutting and turning, which involve the external rotators of the hip (eg, piriformis, gluteus medius). The onset of pain is less acute but usually within 24 hours.

What are the symptoms?

The most common presenting symptom is buttock pain of gradual onset that increases with sitting. The "wallet sign" associated with the syndrome is when a male patient finds he can no longer sit on his wallet without causing symptoms. Paresthesias may develop, but the classic radicular symptoms of sciatica are not common.

Piriformis syndrome in the runner may be associated with foot overpronation, weakness of the gluteal muscles and other hip abductors, and tightness of the hip adductors.

Clinically, the diagnosis of piriformis syndrome is considered when the classic signs of a lumbar radiculopathy elicited by provocative testing are absent, neurologic examination is normal, and other causes of gluteal and sacroiliac pain are ruled out.

Can you test for it during physical examination?

A provocative test (Freiburgs test) suggesting piriformis syndrome is performed by placing the hip in extension and internal rotation, and then resisting external rotation. Pain or sciatic symptoms denotes a positive test . Another test (Pace sign) involves having the seated patient resist abduction and external rotation. Pain and reproduction of symptoms marks a positive test.

Are there any imaging tests?

When necessary, plain radiographs and MRI of the hip and pelvis are obtained to rule out other causes of symptoms. EMG and nerve conduction studies are rarely positive in piriformis syndrome but can be useful for eliminating other diagnostic possibilities.

What is the treatment?

Treatment begins with physical therapy involving strengthening of the pelvic and hip region and stretching of the piriformis. Physical therapy is effective in the majority of cases.

YouTube search shows same of the exercises: https://www.youtube.com/results?search_query=piriformis+syndrome+exercises Always consider consulting a professional before any treatment is started.

The mainstay of treatment for both gluteus medius tendinopathy and piriformis syndrome is physical therapy and correction of biomechanical abnormalities. Orthotics and massage therapy may be useful; acetaminophen and nonsteroidal antiinflammatory drugs may be used for analgesia.

Ultrasound-guided glucocorticoid injections have been beneficial in some cases, and botulinum toxin injections have also been used. Surgery (typically a piriformis tenotomy) may be considered if symptoms are debilitating and persist despite conservative therapy.

Gluteus medius weakness and tendinopathy

The gluteus medius muscle originates along the external surface of the ilium and runs distally and laterally to its attachment on the greater trochanter of the femur. The gluteus medius abducts the hip and assists with pelvic stability during running. Weakness of the muscle causes pain with hip abduction and rotation. Pain generally increases when the muscle is stretched and there may be focal tenderness at the muscle's insertion, just medial and superior to the greater trochanter. Difficulty maintaining a level pelvis while standing on one leg is called positive Trendelenburg sign.

References:

https://www.uptodate.com/contents/overview-of-running-injuries-of-the-lower-extremity
https://www.uptodate.com/contents/approach-to-hip-and-groin-pain-in-the-athlete-and-active-adult

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Canned tuna is struggling to connect with younger generation

From the WSJ:

"Canned tuna is struggling to connect with younger generations who favor fresher, less-processed options."

In a country focused on convenience, canned tuna isn’t cutting it with consumers. “A lot of millennials don’t even own can openers,” said vice president for StarKist.

Younger consumers are opting for fresh or frozen fish over canned items.

Tuna first made inroads into American cupboards following a sardine shortage in 1903 and grew in popularity during wartime protein shortages that followed and as new canning technologies took hold. Since the late 1980s, its reputation has changed as consumers worried about potential mercury poisoning, the harm done to dolphins and its likeness to cat food.

Companies see promise in pouches vs. cans.

New cups of flavored tuna are designed to fit in car cupholders and are equipped with a plastic fork.

References:

https://www.wsj.com/articles/tuna-makers-look-to-hook-younger-consumers-1543766400

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