CR4 - CR4 - Caleb Finch

(Summary by Andrea Feucht)

Meat-adaptive genes

Jean Calment: 122 years, no dementia – smoked until 112yo & drank daily

Eukaryotes have same cell structure & biochem, but range of lifespans is one million-fold: yeast 2 days to conifers 5000 years.

Primate phylogeny and Alzheimer changes – have the same Abeta sequence.

Mouse lemur: has Alzheimer-like changes at very early age, only 2x puberty age and long before maximum life span.

In humans, the largest cause of death after age 50 is vascular (3x that of cancer). Arterial lesions begin at/before birth, and just increase throughout life, ultimately killing most people. They start out microscopic and as “foam cells”. That changes to real lesions and hardening which is effectively scar tissue (healing attempts). The rate of this change is tied to both diet and genetics; essentially it is an inflammation and overheating response.

Blood pressure increases with age as a fairly linear progression across many studies, from average 110 systolic at age 20 vs 150 at age 75. The mortality risk of high systolic bp increases exponentially with age, rather than mathematically.

The inflammatory mechanisms seem to often be tied to the rate of senility – the key point of this speech?

Senilic regression begins at age 30, at ½ % per year (?). Two controlling factors are diet and “infectious load” on the system.

Anti-inflammatory supplements: have strong protection against both vascular trouble and dementia…. Such as:

• aspirin and statins: 30-50% reduction in both CVD and breast cancer
• nsaids (ibuprofen) reduce colorectal cancer by 30-50%, and also plaque formation
• alternative: CR does the exact same thing as ibuprofen relating to plaque formation.

[Luigi says there might be a paper that says chronic aspirin consumption might not have a good long term effect – might even be bad…. This study needs to be looked into.]

Evolution of Human Life Span:

• human-chimp life span was about 25 (max 50)
• genus homo is unknown
• homo sapiens is also unknown
• foragers & pre-industrial was 40 years (max 80)
• industrial & modern medicine is 80 (max 122 thus far)
• current/future regenerative medicine is unknown

Chimp-human ancestor was almost certainly total vegan (raw food – berries, nuts). Stone tools and fire did not correlate with increased brain size, but spears and their use did – is this significant? We also seem to be on a gradual change from that veganism to something far closer to pure carnivorism in present time.

Types of meat eaten range from insects only in gorillas, to adding lots of tissues by the chimp such as brains, muscle, marrow, human offspring, etc. Primary chimp food is still ripe fruit with some insect supplementation, but up to 70g of meat per day by males. Females beg for meat but not when pregnant or nursing (???). This is “cultural” habit, as some chimp communities do not hunt or eat meat at all.

Australopithecus diet is unknown mostly.

WE on the other hand, prefer high-meat, high fat diet when offered. This could be related to our other differences such as slower development (later age of successful reproduction relative to age of puberty, later full ‘acceptance’ into adult community), large brains, multi-generational caregiving and LONGER life span.

So, WHY is eating meat/fat better? Possibly it allowed us to actually spend time on STUFF – cultural development, setting up permanent home sites, language, art. Apes spend 6-10 hours per day eating, we can eat full caloric requirements in 10-30 minutes.

Chimps both age faster than (foraging, pre modern medicine) humans and they have higher mortality rates at all ages across the entire life span. Physical degeneration happens much earlier, such as tooth abscesses and skin wrinkles and bone degeneration – this is similar to pre-industrial humans but still worse. In reproduction, men degenerate earlier, but women are far later – same age as modern humans (40-50 years menopause) – this is very weird.

Chimps in captivity also have higher CVD mortality than any other nonhuman primate – they just drop dead a lot more often, especially when they eat animal tissues.

Dangers of eating meat: cholesterol elevations; infectious agents (parasites and viruses/prions).

Natural defenses & adaptations from our genes:

• apoE3 – lowers cholesterol and increases neuron growth; there is also apoE4 which arose earlier but not as effective.
• detox genes – can absorb excess iron and copper
• immune defense – protect from prions and viruses
• antioxidant genes – slow the damage to blood vessels

Lipoprotein gene variants also influence blood lipid response to diet, especially dietary fat rather than meat protein.

Large breasts are a metabolic adaptive response – not seen in great apes; signals that the woman can survive a famine and still rear a child. Makes her more marriageable….

Mortality risk relative to BMI: (Flegal KM et al. JAMA; 293:1861-7; 2005) It seems to be increased only at below 19 BMI and above 30 or even 35.

For the future – the positive aspects are new drugs (CR mimetics) and regenerative medicine. Negative aspects are the obesity epidemic, air pollution and inflammagens, new infectious diseases which can spread much more rapidly than in the past.