Would you like to live longer? If you’re like me, the answer is an emphatic YES!!!
Of course, you want to be healthy for the vast majority of the time. No one wants to live to 100 but spend 40 years being dragged across the finish line with numerous chronic diseases.
Unfortunately, it’s hard to do longevity studies in humans. First, the studies take a long time. Secondly, you have to find those willing to have portions of their life controlled. Finally, those people need a lot of faith that the intervention will work, and what about those in the placebo group?
At any rate, there are a few things we find that seem to be conserved across many species. Calorie restriction is one. Additionally, exercise seems to be the most effective option to delay aging in humans.
We often look to these various conserved mechanisms across animal species to get an idea as to what might help us live longer. A recent paper took a look at genetic factors that contribute to longevity in various mammal species.
What they found was pretty interesting, and does seem to back up a lot of what we suspect is important for us. Let’s dig in!
What makes some mammals live longer than others?
There is a wide range of maximum lifespan in various species of mammal. Looking at the molecular differences in these mammals gives us clues as to what causes longer-lived to animals to stick around longer.
In this paper, they found two separate groups of genes that regulate maximum lifespan. On the one hand, negatively-associated maximum lifespan genes reduce lifespan. This means that higher expression of these genes leads to a shorter lifespan.
On the other hand, positively-associated maximum lifespan genes increase lifespan. This means that increased expression of these genes increases lifespan.
Not surprisingly, they found both energy metabolism and inflammation negatively associated with lifespan. Put another way, animals with a slower metabolism and lower inflammation live longer.
As far as positively-associated genes, increased expression of genes involved in DNA repair, RNA transport, and microtubule organization increased lifespan. This makes sense because they all play a role in the integrity of DNA.
So basically, if your goal is to live longer, you want a slower metabolism, lower inflammation, and efficient and healthy DNA.
Two separate networks regulate these genes
Interestingly, the authors pinpoint how 2 separate networks control these genes. The negatively-associated genes are under circadian regulation. They believe putting them under circadian regulation allows animals to avoid persistently elevated levels.
This jibes with evidence that mice with an intrinsic circadian period closer to 24 hours live 20% longer than those that don’t. These mice are aligned to the 24 hour day/night cycle no matter what. Therefore, disruption will have less of a negative effect on them.
Of course, a constant circadian environment and lifestyle should yield the same phenotype, so living a lifestyle with strong & consistent circadian exposures(Light, exercise, feeding) should yield similar results. In other words, observe strong circadian habits.
The second network is the pluripotency network. The pluripotency network regulates the self-renewal and differentiation of stem cells. Increased expression of the regulatory genes in this network helps maintain stem cell pools and the regenerative capacity of our organs and tissues.
Unfortunately, we don’t have a ton of control over the pluripotency network. You certainly want to limit DNA damage and do what you can to enhance DNA repair processes.
We have very few options here, but the really cool stuff is coming with cellular reprogramming via Yamanaka factors. Not currently ready for prime time, but possibly within our lifetime.
This new evidence on the gene networks that cause some animals to live longer than others supports other evidence on longevity. Furthermore, it supports some of the interventions we suspect will help in humans.
To date, in all model organisms, calorie restriction leads to extended lifespan. Not surprisingly, calorie restriction also leads to a slower metabolism and reduced inflammation.
This also supports the idea that exercise is critically important for us as we grow older. When we’re young, DNA repair processes and the integrity of DNA as a whole are fantastic. But, as we age, there is a gradual decline.
However, exercise seems to both reduce DNA damage AND enhances DNA repair capacity after radiation-induced damage. This is a central component of the active grandparent hypothesis, which simply states that greater levels of physical activity are essential for healthy aging as they shift resources from fertility and growth towards maintenance and repair.
So if you’re looking to live longer and more healthy, it’s essential to:
- Be physically active, particularly as you age
- Consume a level of calories that leads to a healthy weight, reduces metabolism & inflammation
- Practice good circadian habits
We’ll cover some foods to increase or limit that may be able to goose some of this along in a future blog.