Cellular and molecular longevity pathways: the old and the new

• Stress responses influence aging via systemic effects.
• Complex interplay between genetic, genomic, and epigenetic factors determines longevity.
• Aging stem cells display reduced differentiation and unresponsiveness to cues.
• The microbiota emerges as a crucial determinant of aging and frailty.

Human lifespan has been increasing steadily during modern times, mainly due to medical advancements that combat infant mortality and various life-threatening diseases. However, this gratifying longevity rise is accompanied by growing incidences of devastating age-related pathologies. Understanding the cellular and molecular mechanisms that underlie aging and regulate longevity is of utmost relevance towards offsetting the impact of age-associated disorders and increasing the quality of life for the elderly. Several evolutionarily conserved pathways that modulate lifespan have been identified in organisms ranging from yeast to primates. Here we survey recent findings highlighting the interplay of various genetic, epigenetic, and cell-specific factors, and also symbiotic relationships, as longevity determinants. We further discuss outstanding matters within the framework of emerging, integrative views of aging.