#357- a new era of longevity science: models of aging, human trials of rapamycin, biological clocks, promising compounds, and lifestyle

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How do we lower the “Noise in the System”

Gompertz's law refers to the mathematical principle describing how mortality rates increase exponentially with age, particularly in adult humans between about 30 and 90 years old

Homeostasis-process by which living organisms maintain a stable and balanced internal environment, such as temperature, pH, and fluid balance, despite changes in external conditions. This regulatory mechanism ensures that body systems function optimally and that the organism survives and thrives

Stochastic- Stochastic describes any process, event, or system that is randomly determined or has an element of randomness or probability, rather than being completely predictable or deterministic. In biological and scientific contexts, stochastic processes or events are those subject to chance fluctuations—meaning their outcomes cannot be precisely predicted, only described in terms of probabilities

MTOR-In "Outlive," Peter Attia describes mTOR (mechanistic Target Of Rapamycin) as a critical cellular protein complex that acts as a “master regulator” of cell growth, metabolism, and aging by sensing and integrating nutrient signals.

How mTOR Works

mTOR functions as the cell’s general contractor, deciding when the cell switches between growth (anabolism) and breakdown/recycling (catabolism).
It receives signals about the availability of nutrients (like amino acids, glucose, and insulin) and then coordinates a range of downstream processes — most notably when to build new proteins, repair tissues, or initiate cellular division.
mTOR forms two distinct protein complexes in cells, mTORC1 and mTORC2, which respond differently to nutrients and growth signals.

mTOR, Aging, and Longevity

Attia highlights that mTOR is central in linking nutrient availability to aging and healthspan.
Overactivation of mTOR, often from constant nutrient surplus in modern diets, drives excessive cell growth and impairs the body’s ability to carry out autophagy (the “recycling” of cell components needed for cellular repair).
Interventions such as fasting, protein restriction, and certain drugs (notably rapamycin) can “turn down” mTOR activity. This increases healthspan and, in animal studies, extends lifespan by promoting beneficial stress responses and cellular maintenance.

Key Insights from "Outlive"

Attia cautions that both extremes — chronically high or low mTOR activity — have tradeoffs. High mTOR activity results in rapid aging and risk of cancer, while chronically low activity can impair growth, immunity, and wound healing.
He underscores the importance of balance: transiently lowering mTOR (e.g., via intermittent fasting or strategic nutrient restriction) appears beneficial for longevity, but chronic suppression may have downsides.

Peter Attia’s presentation of mTOR in "Outlive" frames it as a central switch that integrates nutrition, growth, and the process of aging, with immense potential for optimizing both lifespan and healthspan

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