Anti-aging or Optimum Metabolic Health in 3 Steps

Why age related decline in...

Melatonin is one axis leading to aging.

NAD age related decline in NAD is a second axis leading to aging.

Loss of protein quality control or proteostasis is a third axis of aging.

Therefore, the 1,2,3 of anti aging is the following:

Melatonin.

NR niccotinamide riboside.

Spermidine, wheat germ.

Death and frailty result from stem cell exhaustion.  This regimen is central to both somatic and stem cells survival and quality control.

https://www.sciencedirect.com/science/article/pii/S1043276018302261

Sirtuins in Metabolic and Epigenetic Regulation of Stem Cells

Highlights

As cellular metabolic and stress sensors, sirtuin family of NAD⁺-dependent deacylases are pivotal regulators of stem cell biology in addition to their well-known roles in metabolic diseases and aging.

Despite their common dependence on cellular NAD⁺, different sirtuins display cell type-specific and/or stage-dependent impacts on stem cell biology in response to various environmental cues.

Nuclear and cytosolic sirtuins modulate pluripotent stem cells and embryogenesis through regulation of pluripotency factors, metabolism, epigenetics, redox homeostasis, and cellular stress response.

Sirtuins maintain self-renewal, quiescence, and regenerative capacity of adult stem cells and protect against adult stem cell depletion in response to stress and aging.

Sirtuins are highly conserved NAD⁺-dependent enzymes that are capable of removing a wide range of lipid lysine acyl-groups from protein substrates in a NAD⁺-dependent manner. These NAD⁺-dependent activities enable sirtuins to monitor cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals. Consequently, sirtuins are important for cell survival, stress resistance, proliferation, and differentiation. In recent years, sirtuins are increasingly recognized as crucial regulators of stem cell biology in addition to their well-known roles in metabolism and aging. This review article highlights our current knowledge on sirtuins in stem cells, including their functions in pluripotent stem cells, embryogenesis, and development as well as their roles in adult stem cell maintenance, regeneration, and aging.