How obesity and aging are interlinked

In the developed world age-related diseases remains the by far largest cause of disease, disability and death. Among the young-old (people aged 60-75), the accelerated aging from poor lifestyle choices tends to be the primary cause of death, mostly cancers, atherosclerotic heart disease and diabetes with other comorbidities. Among the old-old (85+), heart disease that are fibrotic in origin (in addition to atherosclerotic), amyloid-related heart disease, immune system failure and loss of general homeostasis due to frailty becomes major culprits.

While obesity is in theory simple, the abundance of food in society and a dysregulated appetite center in the brain creates a situation where it becomes very hard to regulate one's weight, as a result over 40% of americans are obese.

However this is changing with the past couple years popularity with GLP-1 agonist drugs such as Ozempic, Wegovy and Mounjaro targeting appetite centers in the brain, developed by Big Pharma companies such as Novo Nordisk Foundation 礼来 . Within the aging space companies are also working in this direction, one example is BioAge Labs .

So why exactly does obesity overlap with aging? While this question is too long for a Newsletter (although I could easily write a paper on it), I can list a few reasons why.

• Increased inflammation (obesity increases inflammation leading to systemic degradation of tissue just like aging itself), this also plays an important role in atherosclerosis.
• Too much fat leads to more senescent cells (cellular senescence is a hallmark of aging and one of the most well documented as of present).
• Metabolic dysregulation, excess growth factors leading to cancer and dysregulated nutrient sensing.

This all being said, I want to highly empathize that the main reason for why obesity kills is that it speeds up molecular hallmarks that overlaps with "intrinsic aging". Obesity only rarely kills people while they are in their 20s, although it forms a systemic "breeding ground" for future disease, the ultimate result tends to be a decade shorter lifespan than otherwise together with a lower quality of life.

I'm incredibly excited to see the development of new treatments for metabolic disease as the aging ecosystem grows with a focus on truly curing disease. The stellar Hevolution Foundation in Saudi Arabia is paving the way for the investment in a healthier world without age-related and metabolic disease!