You'd think that having lots of food, warmth, and plentiful oxygen levels would help animals enjoy longer lives. The truth is that those factors invite shorter life spans. Animals that live in freezing waters with food scarcity and low oxygen levels can live hundreds of years, like quahog clams (1).

Longer lives are related to Food scarcity

Lower calorie intake over time leads to longevity. This does not mean that starvation is healthy or that food insecurity is good. What it does mean is that eating less than your body needs will keep the cells healthier over time. Healthier cells equals longevity (2, 3, 4). 

Experimentally, prolonged calorie restriction has been shown to reduce age-associated disease in rodents and monkeys. For example, researchers followed Rhesus monkeys for 20 years. Fifty percent of the control fed animals survived compared with 80% survival of the animals that were given 30% less calories per day. In addition, the calorie-restricted animals had less evidence of  diabetes, cancer, cardiovascular disease, and brain atrophy (5).

Longer lives are related to cold

Multiple species of animals have adapted to cold weather. The ones that come to mind are reptiles, since they are cold-blooded creatures.  Data on reptiles in the wild has found that colder temperatures encourage longer lives (6,7). 

One cool example that highlights the effect of cold temperatures on longevity is that of the freshwater pearl mussel. This species of bivalve mollusk is found at different latitudes. The animals that live in the arctic Russian rivers exhibit five times longer lifespans compared to the same species that live in the warmer river waters in Spain (8). 

Longer lives are related to low oxygen levels

As if food scarcity and cold temperatures were not challenging on their own, some animals have adapted to be able to withstand low levels of oxygen (or no oxygen). This is a key factor for animals to enjoy longer lives: lower oxygen means lower reactive oxygen species. That is a huge advantage as it means that animals experience lower oxidation damage to their cellular systems (9). 

For example, turtles can survive intense environmental conditions. One such turtle (the pond slider/(Trachemys scripta) can live a long time without oxygen (10).  Freshwater turtles hibernate under water to avoid freezing temperatures. They have the ability to stay under the ice for weeks while waiting for the ice to thaw. They do this by decreasing their metabolic rate to 10% of its normal and use stored up glycogen stores to produce glucose through anaerobic (non-oxygen) systems.  

Needless to say, animals that exhibit significant reductions in core body temperatures during hibernation enjoy longer lives (11).

In the same vein, animals that live in Arctic waters have multiple factors in their favor: There is food scarcity in Arctic waters (at the depth where Greenland Sharks and Bowhead whales live); animals live in below freezing environments with lower oxygen levels, and they have low risk of predation (4).

And, left we forget them, the animals discussed in the last article (bats, naked mole rats, and Bowhead whales) are all tolerant to intermittent or continuous hypoxia (12, 13).  

The search for a unifying thesis that explains why some animals have longer lives and others don't continues (1, 4, 14, 15, 16). A very logical explanation from Omotoso and others (4) is that animals adapted to a change in their environment. This adaptation became fixed in their genes as they gained a survival advantage: Those same genes created - as a positive side effect - longer lifespans. This "adaptive hitchike" model helps explain the diversity of research outcomes in aging and longevity. 

Thus, people living in the Tibetan plateau adapted to living at high altitudes. But research also found close-by genes that were able to respond to a hypoxic environment (4). The latter, as we know, is linked to longevity.

I have to say, though, that experiments that  change the environment can induce "healthier" and longer living cells even in short term experiments (17). This suggests that an adaptation process may not need to be invoked. Thus, decreasing calorie intake, placing animals in cold or low oxygen environments shows relatively quick effects at the cellular level, presumably prior to an adaptation response.  This suggests that cold, food-scarce, and oxygen-poor environments may be good for cells and organisms. 

See also this post on two theories of aging Cellular hyper-function and Clean cupboards. 

In humans, studies on calorie restriction over 2 years show improvements in multiple metabolic  markers (18). There is even evidence that atherosclerosis (hardening of the arteries) can be reversed through calorie restriction (19). In that study, eighteen people who had been on a calorie restricted diet for an average of 6 years. were compared to a control group. Their carotid artery wall thickness was 40% lower than the control group. 

Studies have also examined human populations that live in chronic hypoxic conditions, as noted above. People living in the Tibetan Plateau tend to have longer lives than older people living at lower altitudes. In support of this, studies have also documented that Tibetans showed up-regulation of longevity-associated genes. This is the same pattern that has been found in model animals under hypoxic conditions (20). Interestingly, Tibetans also had evidence for a shift towards anaerobic metabolism of glucose (21).

Preventing or minimizing aging as well as increasing longevity through dietary or therapeutic means is the holy grail to combat aging-related disease such as dementia, cardiac disease, and cancer.

Clearly, when cells are given appropriate signals from the environment to stay healthy, they respond by re-engineering their internal structures and processes. 

What is interesting, though, is that the effect of manipulating the environment pales compared to the effect of manipulating the structures and processes at the nuclear level. In the next article, I will describe the incredibly powerful effect of being born with - or having manipulated - the right nuclear infrastructure and blueprint.