Aging

Aging is fundamentally a process of declining oxidative metabolism, characterized by a shift away from efficient mitochondrial energy production toward non-mitochondrial oxidation and a reduced capacity to use oxygen properly. 2 Peat's dissertation work established that the changes causing reproductive senescence occur in every tissue, driven by a common set of chemical and biological processes. 8 He found that aged uterine tissue often consumed oxygen at a high rate, but this was a sign of oxygen wastage under excessive estrogenic influence rather than efficient energy production. 2 The crucial distinction is that while the metabolic rate of remaining active cells does not decline with age, the mass of inert connective tissue increases, and mitochondria lose efficiency or decrease in number. 1 This creates a state where non-mitochondrial oxidation increases as mitochondrial oxidation declines, a pattern Peat connected directly to Otto Warburg's concept of a "respiratory defect" in cancer. 2

The accumulation of polyunsaturated fatty acids (PUFA) in aged cells is now understood to be a central driver of this metabolic decline. 2 Dinkov has written that senescence is characterized by a striking accumulation of PUFA inside cells, which directly compromises the function of cardiolipin, the crucial mitochondrial lipid that stabilizes the inner membrane and carries electrons in the electron transport chain. 2 The more unsaturated the cardiolipin, the more vulnerable it is to oxidative destruction, leading to structural disintegration and less oxidative phosphorylation. 2 Peat had earlier identified that a vitamin E deficiency and excess unsaturated fat both increase oxygen consumption while producing lipofuscin (age pigment), a substance that consumes oxygen and fuel but produces no usable energy. 2 This pigment accumulates in conditions of low oxygen tension, and aged cells become increasingly embedded in dense, cross-linked collagen that creates an oxygen-deprived environment, further suffocating tissues. 2

Estrogen excess emerges as a primary hormonal driver of aging in Peat's framework. 2 He observed that the effects of excessive estrogen stimulation and senescence on tissue structure were remarkably similar, both causing progressive increases in collagen deposits. 1 Estrogen acts in several ways to decrease oxygen availability: it induces an NADH oxidase, stimulates iron absorption (which is involved in the peroxidation that produces lipofuscin), and synergizes with vitamin E deficiency to intensify age pigment formation. 2 The ratio between estrogen and progesterone controls their effects, and progesterone's role is to assure oxygen and nutrient availability while inhibiting lipofuscin formation and other aging signs by improving metabolic efficiency. 4 Peat argued that many features of aging resemble an estrogen excess rather than the estrogen deficiency promoted by the pharmaceutical industry. 4 Stress accelerates these collagen changes, apparently acting through adrenal cortical hormones and estrogen. 1

The metabolic shift underlying aging is now understood through the lens of the Randle Cycle, where increased fat oxidation (FAO) directly competes with and displaces glucose oxidation. 10 Dinkov has explained that increased FAO is sufficient to cause cellular dysfunction and senescence by lowering the FAD/FADH ratio, creating a functional block at complex II of the electron transport chain, and generating reverse electron flow (REF) which produces the vast majority of reactive oxygen species during oxidative phosphorylation. 10 Even saturated fats, when oxidized at the expense of glucose over the long term, can shift the redox balance toward reduction and cause the same metabolic derangements as a standard Western diet. 10 This aligns with Peat's view that oxidizing primarily glucose is of paramount importance for systemic health, and that low metabolism causes oxidative stress, not the reverse as the "rate of living" theory claims. 2 Dinkov has stated that PUFA accumulation is the major cause of cell aging and that reversing that accumulation likely restores a cell's biological age back to youthfulness. 2

The systemic nature of aging is further evidenced by the role of blood-borne factors. Serum from young animals supports better cell growth than serum from older individuals, and the albumin in old blood is in a more oxidized state. 6 Selye's experiments showed that frequent drainage of fluid from isolated tissue filaments prevented age-changes, and a gerontologist reportedly rejuvenated an old dog by repeatedly replacing its blood serum with saline. 6 Peat also noted that the brain and liver regulate glucose and hormones, meaning the conditions under which those organs develop influence later functioning and account for transgenerational effects. 2 The proportionality between onset of sexual maturity and age at reproductive senescence is a recognized genetic and dietary phenomenon, and late maternal age is associated with earlier sexual maturity in offspring, which would be expected if accelerated sexual maturity is linked to reduced lifespan. 5 Every stress leaves an indelible scar, and the organism pays for its survival by becoming a little older. 9