Rapamycin extends life- and health span because it slows aging.

Making headlines, a thought-provocative paper by Neff, Ehninger and coworkers claims that rapamycin extends life span but has limited effects on aging. How is that possibly possible? And what is aging if not an increase of the probability of death with age. I discuss that the JCI paper actually shows that rapamycin slows aging and also extends lifespan regardless of its direct anti-cancer activities. Aging is, in part, MTOR-driven: a purposeless continuation of developmental growth. Rapamycin affects the same processes in young and old animals: young animals' traits and phenotypes, which continuations become hyperfunctional, harmful and lethal later in life.

is associated with systemic hyperfunctions: increased blood pressure (hypertension), increased platelet aggregation (hyper-aggregation), hyper-contractility of arterial smooth muscle cells, hyper-coagulation, hyperlipidemia, hyperglycemia, hyperinsulinemia, increased resistance to hormones, pro-inflammatory conditions, organ hypertrophy, fibrosis and hyperplasia. These hyperfunctions are damaging to the organs and, when damage occurs, then some functions are lost. So only late stages of aging are decline and loss of functions. Terminal stages are MTOR-independent and will not be reversed by rapamycin. For example, hyperfunctional osteoclasts cause osteoporosis, leading to a broken bone and a sequence of events (immobilization, pneumonia, etc), which require standard medical interventions, not anti-aging drugs [60]. Not only in mammals, but also in C elegans and Drosophila, life-limiting pathologies are caused of exacerbated and intensified normal processes and functions [19,25,61,62].

Aging is a quasi-program (not a program)
Why systemic hyperfunctions arise? Aging is an unintended continuation of organismal growth, like cellular senescence is a continuation of cellular growth [63]. In other words, aging is a quasi-program (not a program): an unintended and purposeless continuation of developmental programs, which are not switched off upon their completion [64][65][66][67], causing age-related diseases. For example, blood pressure is increased from birth to adulthood and continuation of this trend leads to hypertension. Menopause is a hyperfunctional continuation of reproductive program [68]. Agingassociated pathologies are continuation of normal functions of the young organism. Therefore, rapamycin must affect the same processes in young and old animals, because aging is a continuation of normal functions. Aging processes do not spring from nothing. They are continuations of normal cellular, tissue, organ and system functions in young animals.
Inhibition of TOR slows aging: converging evidence [124] 1. Rapamycin suppresses geroconversion: conversion from cellular quiescence to senescence. Geroconversion is cellular basis of organismal aging 2. Genetic manipulations that inhibit the TOR pathway extend life-span in diverse species from yeast to mammals Aging processes do not spring from nothing. They are continuations of normal cellular, tissue, organ and system functions in young animals. Unless miracle is possible, rapamycin must affect the same processes in old and young animals. And it does.
Rapamycin extends life span independently of its anti-cancer effect and prevents cancer by slowing down aging.
www.impactaging.com 3. Rapamycin extends lifespan in all species tested 4. Calorie restriction, which inhibits MTOR, extends lifespan 5. MTOR is involved in diseases of aging and rapamycin prevents these diseases in animal models

Rapamycin slows aging: the JCI paper [2]
How does the Neff et al study support the model of quasi-programmed aging?
1. As shown by Neff et al, chronic administration of rapamycin extends lifespan in male C57BL/6J mice, when started at both young and old age. Note: This extension is impressive given that (a) effects of rapamycin in male mice are blunted compared with female mice in previous studies, (b) C57BL/6J mice are intrinsically long-lived and (c) rapamycin was administrated in everyday schedule (chronic or immunosuppressive schedule) instead of intermittent or pulse administration (anti-aging schedule). 2. C57BL/6J mice are refractory to many tumors http://jaxmice.jax.org/strain/000664.html Therefore, life extension is difficult to explain by anticancer effects of rapamycin. 3. In fact, rapamycin did not prevent cancer when the treatment was started at middle and old age, but still extended life span. As stated by Neff et al [2]: "Rapamycin … had no measurable effect in the 25month cohort (vehicle, 1 of 5; rapamycin, 2 of 8; P = 1.0, Fisher exact test) or the 34-month cohort (vehicle, 1 of 5; rapamycin, 3 of 10; P = 1.0, Fisher exact test)." As we discussed here, this indicates that effects of rapamycin are probably due to suppression of aging. Rapamycin treatment decreased cancer incidence only when it was started in young mice.

4.
Rapamycin counteracted certain aging-related alterations in both young and old mice. This suggests that aging is a continuation of normal traits in young organisms. Aging is driven by intensified and exacerbated normal cellular functions. 5. Rapamycin did not affect many parameters that are not aging-specific such as alterations in plasma sodium, calcium and chloride concentrations. This is expectable. Aging is not associated with alterations of electrolyte homeostasis. These alterations are terminal phases of medical conditions due to organ (e.g. renal) failure. 6. Some age-related alterations actually counteract aging. For example, although RNA/protein synthesis is decreased with aging in model organisms, yet its further inhibition prolongs life span further [138][139][140][141]