Aging or Jara-related changes affect almost all organisms. However, possibilities of long healthy life, age-reversal, or even immortality have either been postulated or experimentally observed based on changes in the molecular cascades and hierarchy from the cell cycle to cell death during development and after birth. Expression of some proteins is autoregulated, and many are multifunctional, like Paired box (Pax) proteins, tumor necrosis factors, interferons, cytokines, chemokines, trophic- or transforming growth factors, and p53. They function as regulator of other genes and proteins that are required for cellular growth, maturation, differentiation, and the creation of cellular identity. This chapter explains the literature and experiment-based importance of available natural and commercial supplements, their bioactive compounds, metabolites, chemical scaffolds, and ayurvedic formulations like Chyawanprash, Triphala Rasayan, Brahmi Ghrita, Ashwagandharishta, Saraswatarishta, Amalaki Rasayana, and Medhya Rasayana, as a safe alternative source for a healthy brain and longevity. These compounds and formulations outdo the single-component therapies, offering multi-target and systems-level effects on the management or therapy of stress and inflammation, dysbiosis, synaptic plasticity, repair of genetic components, energy homeostasis, and geriatric care. A comprehensive understanding on a reactive disease management model to a proactive approach would be helpful in the preservation of vitality, healthy systems biology and longevity.